Mycoses

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

The U.S. Food and Drug Administration is declining to approve the investigational antifungal olorofim and is asking for more data, according to a news release from the manufacturer, F2G.

Olorofim, (formerly known as F901318) is the first in the orotomide class of antifungals to be evaluated clinically for the treatment of invasive mold infections. Its maker, F2G, is a biotech company based in Manchester, England, that focuses on developing drugs for rare fungal diseases.

The company says it remains optimistic and will address the FDA’s requirements and continue to seek approval.

The FDA’s denial comes as fungal infections are becoming increasingly common and resistant to treatment. There are only four antifungal classes currently available, and there are few new candidates in the pipeline. No new classes of antifungals have been developed in 2 decades.

David Andes, MD, chief of the division of infectious diseases at the University of Wisconsin–Madison, told this news organization he shares the hope that the company can meet the requirements to gain approval.

“Some of the early results were really exciting,” he said. “People are enthusiastic about the compound because it has a novel mechanism of action, and it is active against a group of fungi that we have limited to no options for.”
 

Early results ‘exciting’

Dr. Andes said several physicians have been able to prescribe olorofim under the compassionate use program “and have witnessed success.”

Olorofim is the first antifungal agent to be granted breakthrough therapy designation, which the FDA granted in November 2019 for the treatment of invasive mold infections for patients with limited or no treatment options, including patients with refractory aspergillosis or those who are intolerant of currently available therapy. It is also indicated for infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species.

Olorofim received a second breakthrough therapy designation in October 2020. The second designation was granted for treatment of central nervous system coccidioidomycosis that is refractory or for cases that cannot be treated with standard-of-care therapy.

It is very difficult for patients to be approved to receive compassionate use medicines, Dr. Andes pointed out. “I’d like to have access sooner rather than later,” he added.

Dr. Andes says the drugs are expensive and are time consuming to produce. And with antifungals, it is difficult to demonstrate safety in comparison with other antimicrobial agents because “it’s hard to hurt a fungus without having toxicity with human cells.”
 

Complete response letter issued

F2G received a complete response letter from the FDA regarding its new drug application for olorofim, according to the news release issued by the company. “While F2G is disappointed with this outcome, we remain optimistic about olorofim’s potential to address an unmet need for patients with invasive fungal infections who have exhausted their treatment alternatives,” Francesco Maria Lavino, chief executive officer, said in the release. “We are assessing the details of the Complete Response Letter, and we plan to meet with the FDA to discuss it further.”

Dr. Andes says few other antifungals have made it as far as olorofim in clinical trials.

Lance B. Price, PhD, codirector of the Antibiotic Resistance Action Center at George Washington University in Washington, told this news organization that despite the lack of antifungals in the pipeline, “We can’t allow our desperation to override the checkpoints that ensure that antifungals are safe to use in people.”

In the meantime, he said, it is important to preserve the utility of current antifungals by avoiding overusing them in medicine and agriculture.

“Sadly,” he said, “a drug called ipflufenoquin, which works by a similar mode of action as olorofim, has already been approved by the U.S. Environmental Protection Agency for use in plant agriculture. This could weaken the effectiveness of olorofim for treating things like Aspergillus infections even before the drug has been approved for use in humans.”
 

Plant drug undermining olorofim efficacy in humans

“While I’m sure this makes financial sense for the makers of ipflufenoquin, it borders on insanity from a public health perspective,” Dr. Price said.

Meanwhile, the global threat of fungal infections grows. The World Health Organization has launched its first-ever list of health-threatening fungi. Authors of a WHO report that contains the list write, “The invasive forms of these fungal infections often affect severely ill patients and those with significant underlying immune system–related conditions.”

F2G will continue to expand olorofim’s clinical trial program, according to the company’s statement. Along with its partner, Shionogi, it is enrolling patients with proven or probable invasive aspergillosis in a global phase 3 trial (OASIS), which will compare outcomes after treatment with olorofim in comparison with amphotericin B liposome (AmBisome) followed by standard of care.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration is declining to approve the investigational antifungal olorofim and is asking for more data, according to a news release from the manufacturer, F2G.

Olorofim, (formerly known as F901318) is the first in the orotomide class of antifungals to be evaluated clinically for the treatment of invasive mold infections. Its maker, F2G, is a biotech company based in Manchester, England, that focuses on developing drugs for rare fungal diseases.

The company says it remains optimistic and will address the FDA’s requirements and continue to seek approval.

The FDA’s denial comes as fungal infections are becoming increasingly common and resistant to treatment. There are only four antifungal classes currently available, and there are few new candidates in the pipeline. No new classes of antifungals have been developed in 2 decades.

David Andes, MD, chief of the division of infectious diseases at the University of Wisconsin–Madison, told this news organization he shares the hope that the company can meet the requirements to gain approval.

“Some of the early results were really exciting,” he said. “People are enthusiastic about the compound because it has a novel mechanism of action, and it is active against a group of fungi that we have limited to no options for.”
 

Early results ‘exciting’

Dr. Andes said several physicians have been able to prescribe olorofim under the compassionate use program “and have witnessed success.”

Olorofim is the first antifungal agent to be granted breakthrough therapy designation, which the FDA granted in November 2019 for the treatment of invasive mold infections for patients with limited or no treatment options, including patients with refractory aspergillosis or those who are intolerant of currently available therapy. It is also indicated for infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species.

Olorofim received a second breakthrough therapy designation in October 2020. The second designation was granted for treatment of central nervous system coccidioidomycosis that is refractory or for cases that cannot be treated with standard-of-care therapy.

It is very difficult for patients to be approved to receive compassionate use medicines, Dr. Andes pointed out. “I’d like to have access sooner rather than later,” he added.

Dr. Andes says the drugs are expensive and are time consuming to produce. And with antifungals, it is difficult to demonstrate safety in comparison with other antimicrobial agents because “it’s hard to hurt a fungus without having toxicity with human cells.”
 

Complete response letter issued

F2G received a complete response letter from the FDA regarding its new drug application for olorofim, according to the news release issued by the company. “While F2G is disappointed with this outcome, we remain optimistic about olorofim’s potential to address an unmet need for patients with invasive fungal infections who have exhausted their treatment alternatives,” Francesco Maria Lavino, chief executive officer, said in the release. “We are assessing the details of the Complete Response Letter, and we plan to meet with the FDA to discuss it further.”

Dr. Andes says few other antifungals have made it as far as olorofim in clinical trials.

Lance B. Price, PhD, codirector of the Antibiotic Resistance Action Center at George Washington University in Washington, told this news organization that despite the lack of antifungals in the pipeline, “We can’t allow our desperation to override the checkpoints that ensure that antifungals are safe to use in people.”

In the meantime, he said, it is important to preserve the utility of current antifungals by avoiding overusing them in medicine and agriculture.

“Sadly,” he said, “a drug called ipflufenoquin, which works by a similar mode of action as olorofim, has already been approved by the U.S. Environmental Protection Agency for use in plant agriculture. This could weaken the effectiveness of olorofim for treating things like Aspergillus infections even before the drug has been approved for use in humans.”
 

Plant drug undermining olorofim efficacy in humans

“While I’m sure this makes financial sense for the makers of ipflufenoquin, it borders on insanity from a public health perspective,” Dr. Price said.

Meanwhile, the global threat of fungal infections grows. The World Health Organization has launched its first-ever list of health-threatening fungi. Authors of a WHO report that contains the list write, “The invasive forms of these fungal infections often affect severely ill patients and those with significant underlying immune system–related conditions.”

F2G will continue to expand olorofim’s clinical trial program, according to the company’s statement. Along with its partner, Shionogi, it is enrolling patients with proven or probable invasive aspergillosis in a global phase 3 trial (OASIS), which will compare outcomes after treatment with olorofim in comparison with amphotericin B liposome (AmBisome) followed by standard of care.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration is declining to approve the investigational antifungal olorofim and is asking for more data, according to a news release from the manufacturer, F2G.

Olorofim, (formerly known as F901318) is the first in the orotomide class of antifungals to be evaluated clinically for the treatment of invasive mold infections. Its maker, F2G, is a biotech company based in Manchester, England, that focuses on developing drugs for rare fungal diseases.

The company says it remains optimistic and will address the FDA’s requirements and continue to seek approval.

The FDA’s denial comes as fungal infections are becoming increasingly common and resistant to treatment. There are only four antifungal classes currently available, and there are few new candidates in the pipeline. No new classes of antifungals have been developed in 2 decades.

David Andes, MD, chief of the division of infectious diseases at the University of Wisconsin–Madison, told this news organization he shares the hope that the company can meet the requirements to gain approval.

“Some of the early results were really exciting,” he said. “People are enthusiastic about the compound because it has a novel mechanism of action, and it is active against a group of fungi that we have limited to no options for.”
 

Early results ‘exciting’

Dr. Andes said several physicians have been able to prescribe olorofim under the compassionate use program “and have witnessed success.”

Olorofim is the first antifungal agent to be granted breakthrough therapy designation, which the FDA granted in November 2019 for the treatment of invasive mold infections for patients with limited or no treatment options, including patients with refractory aspergillosis or those who are intolerant of currently available therapy. It is also indicated for infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species.

Olorofim received a second breakthrough therapy designation in October 2020. The second designation was granted for treatment of central nervous system coccidioidomycosis that is refractory or for cases that cannot be treated with standard-of-care therapy.

It is very difficult for patients to be approved to receive compassionate use medicines, Dr. Andes pointed out. “I’d like to have access sooner rather than later,” he added.

Dr. Andes says the drugs are expensive and are time consuming to produce. And with antifungals, it is difficult to demonstrate safety in comparison with other antimicrobial agents because “it’s hard to hurt a fungus without having toxicity with human cells.”
 

Complete response letter issued

F2G received a complete response letter from the FDA regarding its new drug application for olorofim, according to the news release issued by the company. “While F2G is disappointed with this outcome, we remain optimistic about olorofim’s potential to address an unmet need for patients with invasive fungal infections who have exhausted their treatment alternatives,” Francesco Maria Lavino, chief executive officer, said in the release. “We are assessing the details of the Complete Response Letter, and we plan to meet with the FDA to discuss it further.”

Dr. Andes says few other antifungals have made it as far as olorofim in clinical trials.

Lance B. Price, PhD, codirector of the Antibiotic Resistance Action Center at George Washington University in Washington, told this news organization that despite the lack of antifungals in the pipeline, “We can’t allow our desperation to override the checkpoints that ensure that antifungals are safe to use in people.”

In the meantime, he said, it is important to preserve the utility of current antifungals by avoiding overusing them in medicine and agriculture.

“Sadly,” he said, “a drug called ipflufenoquin, which works by a similar mode of action as olorofim, has already been approved by the U.S. Environmental Protection Agency for use in plant agriculture. This could weaken the effectiveness of olorofim for treating things like Aspergillus infections even before the drug has been approved for use in humans.”
 

Plant drug undermining olorofim efficacy in humans

“While I’m sure this makes financial sense for the makers of ipflufenoquin, it borders on insanity from a public health perspective,” Dr. Price said.

Meanwhile, the global threat of fungal infections grows. The World Health Organization has launched its first-ever list of health-threatening fungi. Authors of a WHO report that contains the list write, “The invasive forms of these fungal infections often affect severely ill patients and those with significant underlying immune system–related conditions.”

F2G will continue to expand olorofim’s clinical trial program, according to the company’s statement. Along with its partner, Shionogi, it is enrolling patients with proven or probable invasive aspergillosis in a global phase 3 trial (OASIS), which will compare outcomes after treatment with olorofim in comparison with amphotericin B liposome (AmBisome) followed by standard of care.

A version of this article first appeared on Medscape.com.

Pound of flesh buys less prison time

We should all have more Shakespeare in our lives. Yeah, yeah, Shakespeare is meant to be played, not read, and it can be a struggle to herd teenagers through the Bard’s interesting and bloody tragedies, but even a perfunctory reading of “The Merchant of Venice” would hopefully have prevented the dystopian nightmare Massachusetts has presented us with today.

prison bars shadow_web.jpg

The United States has a massive shortage of donor organs. This is an unfortunate truth. So, to combat this issue, a pair of Massachusetts congresspeople have proposed HD 3822, which would allow prisoners to donate organs and/or bone marrow (a pound of flesh, so to speak) in exchange for up to a year in reduced prison time. Yes, that’s right. Give up pieces of yourself and the state of Massachusetts will deign to reduce your long prison sentence.

Oh, and before you dismiss this as typical Republican antics, the bill was sponsored by two Democrats, and in a statement one of them hoped to address racial disparities in organ donation, as people of color are much less likely to receive organs. Never mind that Black people are imprisoned at a much higher rate than Whites.

Yeah, this whole thing is what people in the business like to call an ethical disaster.

Fortunately, the bill will likely never be passed and it’s probably illegal anyway. A federal law from 1984 (how’s that for a coincidence) prevents people from donating organs for use in human transplantation in exchange for “valuable consideration.” In other words, you can’t sell your organs for profit, and in this case, reducing prison time would probably count as valuable consideration in the eyes of the courts.

Oh, and in case you’ve never read Merchant of Venice, Shylock, the character looking for the pound of flesh as payment for a debt? He’s the villain. In fact, it’s pretty safe to say that anyone looking to extract payment from human dismemberment is probably the bad guy of the story. Apparently that wasn’t clear.
 

How do you stop a fungi? With a deadly guy

Thanks to the new HBO series “The Last of Us,” there’s been a lot of talk about the upcoming fungi-pocalypse, as the show depicts the real-life “zombie fungus” Cordyceps turning humans into, you know, zombies.

zombie_last_of_us_web.jpg

No need to worry, ladies and gentleman, because science has discovered a way to turn back the fungal horde. A heroic, and environmentally friendly, alternative to chemical pesticides “in the fight against resistant fungi [that] are now resistant to antimycotics – partly because they are used in large quantities in agricultural fields,” investigators at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany, said in a written statement.

We are, of course, talking about Keanu Reeves. Wait a second. He’s not even in “The Last of Us.” Sorry folks, we are being told that it really is Keanu Reeves. Our champion in the inevitable fungal pandemic is movie star Keanu Reeves. Sort of. It’s actually keanumycin, a substance produced by bacteria of the genus Pseudomonas.

Really? Keanumycin? “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles,” lead author Sebastian Götze, PhD, explained.

Dr. Götze and his associates had been working with pseudomonads for quite a while before they were able to isolate the toxins responsible for their ability to kill amoebae, which resemble fungi in some characteristics. When then finally tried the keanumycin against gray mold rot on hydrangea leaves, the intensely contemplative star of “The Matrix” and “John Wick” – sorry, wrong Keanu – the bacterial derivative significantly inhibited growth of the fungus, they said.

Additional testing has shown that keanumycin is not highly toxic to human cells and is effective against fungi such as Candida albicans in very low concentrations, which makes it a good candidate for future pharmaceutical development.

To that news there can be only one response from the substance’s namesake.

High fat, bye parasites

Fat. Fat. Fat. Seems like everyone is trying to avoid it these days, but fat may be good thing when it comes to weaseling out a parasite.

The parasite in this case is the whipworm, aka Trichuris trichiura. You can find this guy in the intestines of millions of people, where it causes long-lasting infections. Yikes … Researchers have found that the plan of attack to get rid of this invasive species is to boost the immune system, but instead of vitamin C and zinc it’s fat they’re pumping in. Yes, fat.

whipworms_web.jpg

The developing countries with poor sewage that are at the highest risk for contracting parasites such as this also are among those where people ingest cheaper diets that are generally higher in fat. The investigators were interested to see how a high-fat diet would affect immune responses to the whipworms.

And, as with almost everything else, the researchers turned to mice, which were introduced to a closely related species, Trichuris muris.

A high-fat diet, rather than obesity itself, increases a molecule on T-helper cells called ST2, and this allows an increased T-helper 2 response, effectively giving eviction notices to the parasites in the intestinal lining.

To say the least, the researchers were surprised since “high-fat diets are mostly associated with increased pathology during disease,” said senior author Richard Grencis, PhD, of the University of Manchester (England), who noted that ST2 is not normally triggered with a standard diet in mice but the high-fat diet gave it a boost and an “alternate pathway” out.

Now before you start ordering extra-large fries at the drive-through to keep the whipworms away, the researchers added that they “have previously published that weight loss can aid the expulsion of a different gut parasite worm.” Figures.

Once again, though, signs are pointing to the gut for improved health.

Pound of flesh buys less prison time

We should all have more Shakespeare in our lives. Yeah, yeah, Shakespeare is meant to be played, not read, and it can be a struggle to herd teenagers through the Bard’s interesting and bloody tragedies, but even a perfunctory reading of “The Merchant of Venice” would hopefully have prevented the dystopian nightmare Massachusetts has presented us with today.

prison bars shadow_web.jpg

The United States has a massive shortage of donor organs. This is an unfortunate truth. So, to combat this issue, a pair of Massachusetts congresspeople have proposed HD 3822, which would allow prisoners to donate organs and/or bone marrow (a pound of flesh, so to speak) in exchange for up to a year in reduced prison time. Yes, that’s right. Give up pieces of yourself and the state of Massachusetts will deign to reduce your long prison sentence.

Oh, and before you dismiss this as typical Republican antics, the bill was sponsored by two Democrats, and in a statement one of them hoped to address racial disparities in organ donation, as people of color are much less likely to receive organs. Never mind that Black people are imprisoned at a much higher rate than Whites.

Yeah, this whole thing is what people in the business like to call an ethical disaster.

Fortunately, the bill will likely never be passed and it’s probably illegal anyway. A federal law from 1984 (how’s that for a coincidence) prevents people from donating organs for use in human transplantation in exchange for “valuable consideration.” In other words, you can’t sell your organs for profit, and in this case, reducing prison time would probably count as valuable consideration in the eyes of the courts.

Oh, and in case you’ve never read Merchant of Venice, Shylock, the character looking for the pound of flesh as payment for a debt? He’s the villain. In fact, it’s pretty safe to say that anyone looking to extract payment from human dismemberment is probably the bad guy of the story. Apparently that wasn’t clear.
 

How do you stop a fungi? With a deadly guy

Thanks to the new HBO series “The Last of Us,” there’s been a lot of talk about the upcoming fungi-pocalypse, as the show depicts the real-life “zombie fungus” Cordyceps turning humans into, you know, zombies.

zombie_last_of_us_web.jpg

No need to worry, ladies and gentleman, because science has discovered a way to turn back the fungal horde. A heroic, and environmentally friendly, alternative to chemical pesticides “in the fight against resistant fungi [that] are now resistant to antimycotics – partly because they are used in large quantities in agricultural fields,” investigators at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany, said in a written statement.

We are, of course, talking about Keanu Reeves. Wait a second. He’s not even in “The Last of Us.” Sorry folks, we are being told that it really is Keanu Reeves. Our champion in the inevitable fungal pandemic is movie star Keanu Reeves. Sort of. It’s actually keanumycin, a substance produced by bacteria of the genus Pseudomonas.

Really? Keanumycin? “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles,” lead author Sebastian Götze, PhD, explained.

Dr. Götze and his associates had been working with pseudomonads for quite a while before they were able to isolate the toxins responsible for their ability to kill amoebae, which resemble fungi in some characteristics. When then finally tried the keanumycin against gray mold rot on hydrangea leaves, the intensely contemplative star of “The Matrix” and “John Wick” – sorry, wrong Keanu – the bacterial derivative significantly inhibited growth of the fungus, they said.

Additional testing has shown that keanumycin is not highly toxic to human cells and is effective against fungi such as Candida albicans in very low concentrations, which makes it a good candidate for future pharmaceutical development.

To that news there can be only one response from the substance’s namesake.

High fat, bye parasites

Fat. Fat. Fat. Seems like everyone is trying to avoid it these days, but fat may be good thing when it comes to weaseling out a parasite.

The parasite in this case is the whipworm, aka Trichuris trichiura. You can find this guy in the intestines of millions of people, where it causes long-lasting infections. Yikes … Researchers have found that the plan of attack to get rid of this invasive species is to boost the immune system, but instead of vitamin C and zinc it’s fat they’re pumping in. Yes, fat.

whipworms_web.jpg

The developing countries with poor sewage that are at the highest risk for contracting parasites such as this also are among those where people ingest cheaper diets that are generally higher in fat. The investigators were interested to see how a high-fat diet would affect immune responses to the whipworms.

And, as with almost everything else, the researchers turned to mice, which were introduced to a closely related species, Trichuris muris.

A high-fat diet, rather than obesity itself, increases a molecule on T-helper cells called ST2, and this allows an increased T-helper 2 response, effectively giving eviction notices to the parasites in the intestinal lining.

To say the least, the researchers were surprised since “high-fat diets are mostly associated with increased pathology during disease,” said senior author Richard Grencis, PhD, of the University of Manchester (England), who noted that ST2 is not normally triggered with a standard diet in mice but the high-fat diet gave it a boost and an “alternate pathway” out.

Now before you start ordering extra-large fries at the drive-through to keep the whipworms away, the researchers added that they “have previously published that weight loss can aid the expulsion of a different gut parasite worm.” Figures.

Once again, though, signs are pointing to the gut for improved health.

Pound of flesh buys less prison time

We should all have more Shakespeare in our lives. Yeah, yeah, Shakespeare is meant to be played, not read, and it can be a struggle to herd teenagers through the Bard’s interesting and bloody tragedies, but even a perfunctory reading of “The Merchant of Venice” would hopefully have prevented the dystopian nightmare Massachusetts has presented us with today.

prison bars shadow_web.jpg

The United States has a massive shortage of donor organs. This is an unfortunate truth. So, to combat this issue, a pair of Massachusetts congresspeople have proposed HD 3822, which would allow prisoners to donate organs and/or bone marrow (a pound of flesh, so to speak) in exchange for up to a year in reduced prison time. Yes, that’s right. Give up pieces of yourself and the state of Massachusetts will deign to reduce your long prison sentence.

Oh, and before you dismiss this as typical Republican antics, the bill was sponsored by two Democrats, and in a statement one of them hoped to address racial disparities in organ donation, as people of color are much less likely to receive organs. Never mind that Black people are imprisoned at a much higher rate than Whites.

Yeah, this whole thing is what people in the business like to call an ethical disaster.

Fortunately, the bill will likely never be passed and it’s probably illegal anyway. A federal law from 1984 (how’s that for a coincidence) prevents people from donating organs for use in human transplantation in exchange for “valuable consideration.” In other words, you can’t sell your organs for profit, and in this case, reducing prison time would probably count as valuable consideration in the eyes of the courts.

Oh, and in case you’ve never read Merchant of Venice, Shylock, the character looking for the pound of flesh as payment for a debt? He’s the villain. In fact, it’s pretty safe to say that anyone looking to extract payment from human dismemberment is probably the bad guy of the story. Apparently that wasn’t clear.
 

How do you stop a fungi? With a deadly guy

Thanks to the new HBO series “The Last of Us,” there’s been a lot of talk about the upcoming fungi-pocalypse, as the show depicts the real-life “zombie fungus” Cordyceps turning humans into, you know, zombies.

zombie_last_of_us_web.jpg

No need to worry, ladies and gentleman, because science has discovered a way to turn back the fungal horde. A heroic, and environmentally friendly, alternative to chemical pesticides “in the fight against resistant fungi [that] are now resistant to antimycotics – partly because they are used in large quantities in agricultural fields,” investigators at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany, said in a written statement.

We are, of course, talking about Keanu Reeves. Wait a second. He’s not even in “The Last of Us.” Sorry folks, we are being told that it really is Keanu Reeves. Our champion in the inevitable fungal pandemic is movie star Keanu Reeves. Sort of. It’s actually keanumycin, a substance produced by bacteria of the genus Pseudomonas.

Really? Keanumycin? “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles,” lead author Sebastian Götze, PhD, explained.

Dr. Götze and his associates had been working with pseudomonads for quite a while before they were able to isolate the toxins responsible for their ability to kill amoebae, which resemble fungi in some characteristics. When then finally tried the keanumycin against gray mold rot on hydrangea leaves, the intensely contemplative star of “The Matrix” and “John Wick” – sorry, wrong Keanu – the bacterial derivative significantly inhibited growth of the fungus, they said.

Additional testing has shown that keanumycin is not highly toxic to human cells and is effective against fungi such as Candida albicans in very low concentrations, which makes it a good candidate for future pharmaceutical development.

To that news there can be only one response from the substance’s namesake.

High fat, bye parasites

Fat. Fat. Fat. Seems like everyone is trying to avoid it these days, but fat may be good thing when it comes to weaseling out a parasite.

The parasite in this case is the whipworm, aka Trichuris trichiura. You can find this guy in the intestines of millions of people, where it causes long-lasting infections. Yikes … Researchers have found that the plan of attack to get rid of this invasive species is to boost the immune system, but instead of vitamin C and zinc it’s fat they’re pumping in. Yes, fat.

whipworms_web.jpg

The developing countries with poor sewage that are at the highest risk for contracting parasites such as this also are among those where people ingest cheaper diets that are generally higher in fat. The investigators were interested to see how a high-fat diet would affect immune responses to the whipworms.

And, as with almost everything else, the researchers turned to mice, which were introduced to a closely related species, Trichuris muris.

A high-fat diet, rather than obesity itself, increases a molecule on T-helper cells called ST2, and this allows an increased T-helper 2 response, effectively giving eviction notices to the parasites in the intestinal lining.

To say the least, the researchers were surprised since “high-fat diets are mostly associated with increased pathology during disease,” said senior author Richard Grencis, PhD, of the University of Manchester (England), who noted that ST2 is not normally triggered with a standard diet in mice but the high-fat diet gave it a boost and an “alternate pathway” out.

Now before you start ordering extra-large fries at the drive-through to keep the whipworms away, the researchers added that they “have previously published that weight loss can aid the expulsion of a different gut parasite worm.” Figures.

Once again, though, signs are pointing to the gut for improved health.

COVID-19 has lifted the lid on the risks of secondary pulmonary fungal infections in patients with severe respiratory viral illness – even previously immunocompetent individuals – and highlighted the importance of vigilant investigation to achieve early diagnoses, leading experts say.

Pulmonary_aspergillosis_web.jpg

Most fungi are not under surveillance in the United States, leaving experts without a national picture of the true burden of infection through the pandemic. However, a collection of published case series, cohort studies, and reviews from Europe, the United States, and throughout the world – mainly pre-Omicron – show that fungal disease has affected a significant portion of critically ill patients with COVID-19, with concerning excess mortality, these experts say.

COVID-associated pulmonary aspergillosis (CAPA) has been the predominant fungal coinfection in the United States and internationally. But COVID-associated mucormycosis (CAM) – the infection that surged in India in early 2021 – has also affected some patients in the United States, published data show. So have Pneumocystitis pneumonia, cryptococcosis, histoplasmosis, and Candida infections (which mainly affect the bloodstream and abdomen), say the experts who were interviewed.

Thompson_George_web.jpg

“We had predicted [a rise in] aspergillosis, but we saw more than we thought we’d see. Most fungal infections became more common with COVID-19,” said George Thompson, MD, professor of clinical medicine at the University of California, Davis, and cochair of the University of Alabama–based Mycoses Study Group Education Committee, a group of experts in medical mycology. Pneumocystitis, for instance, “has historically been associated with AIDS or different types of leukemia or lymphoma, and is not an infection we’ve typically seen in our otherwise healthy ICU patients,” he noted. “But we did see more of it [with COVID-19].”

More recently, with fewer patients during the Omicron phase in intensive care units with acute respiratory failure, the profile of fungal disease secondary to COVID-19 has changed. Increasing proportions of patients have traditional risk factors for aspergillosis, such as hematologic malignancies and longer-term, pre-COVID use of systemic corticosteroids – a change that makes the contribution of the viral illness harder to distinguish.

Moving forward, the lessons of the COVID era – the fungal risks to patients with serious viral infections and the persistence needed to diagnose aspergillosis and other pulmonary fungal infections using bronchoscopy and imperfect noninvasive tests – should be taken to heart, experts say.

“Fungal diseases are not rare. They’re just not diagnosed because no one thinks to look for them,” said Dr. Thompson, a contributor to a recently released World Health Organization report naming a “fungal priority pathogens” list.

“We’re going to continue to see [secondary fungal infections] with other respiratory viruses,” he said. And overall, given environmental and other changes, “we’re going to see more and more fungal disease in the patients we take care of.”


 

CAPA not a surprise

CAPA is “not an unfamiliar story” in the world of fungal disease, given a history of influenza-associated pulmonary aspergillosis (IAPA), said Kieren A. Marr, MD, MBA, adjunct professor of medicine and past director of the transplant and oncology infectious diseases program at Johns Hopkins University, Baltimore, who has long researched invasive fungal disease.

Marr_Kieran_web.jpg

European researchers, she said, have led the way in describing a high incidence of IAPA in patients admitted to ICUs with influenza. In a retrospective multicenter cohort study reported in 2018 by the Dutch-Belgian Mycosis Study group, for instance, almost 20% of 432 influenza patients admitted to the ICU, including patients who were otherwise healthy and not immunocompromised, had the diagnosis a median of 3 days after ICU admission. (Across other cohort studies, rates of IAPA have ranged from 7% to 30%.)

Mortality was significant: 51% of patients with influenza and invasive pulmonary aspergillosis died within 90 days, compared with 28% of patients with influenza and no invasive pulmonary aspergillosis.

Reports from Europe early in the pandemic indicated that CAPA was a similarly serious problem, prompting establishment at Johns Hopkins University of an aggressive screening program utilizing biomarker-based testing of blood and bronchoalveolar lavage (BAL) fluid. Of 396 mechanically ventilated COVID-19 patients admitted to Johns Hopkins University hospitals between March and August 2020, 39 met the institution’s criteria for CAPA, Dr. Marr and her colleagues reported this year in what might be the largest U.S. cohort study of CAPA published to date.

“We now know definitively that people with severe influenza and with severe COVID also have high risks for both invasive and airway disease caused by airborne fungi, most commonly aspergilliosis,” Dr. Marr said.

More recent unpublished analyses of patients from the start of the pandemic to June 2021 show persistent risk, said Nitipong Permpalung, MD, MPH, assistant professor in transplant and oncology infectious diseases at Johns Hopkins University and lead author of the cohort study. Among 832 patients with COVID-19 who were mechanically ventilated in Johns Hopkins University hospitals, 11.8% had CAPA, he said. (Also, 3.2% had invasive candidiasis, and 1.1% had other invasive fungal infections.)

Other sources said in interviews that these CAPA prevalence rates generally mirror reports from Europe, though some investigators in Europe have reported CAPA rates more toward 15%.

(The Mycoses Study Group recently collected data from its consortium of U.S. medical centers on the prevalence of CAPA, with funding support from the CDC, but at press time the data had not yet been released. Dr. Thompson said he suspected the prevalence will be lower than earlier papers have suggested, “but still will reflect a significant burden of disease.”)

Patients in the published Johns Hopkins University study who had CAPA were more likely than those with COVID-19 but no CAPA to have underlying pulmonary disease, liver disease, coagulopathy, solid tumors, multiple myeloma, and COVID-19–directed corticosteroids. And they had uniformly worse outcomes with regards to severity of illness and length of intubation.

How much of CAPA is driven by the SARS-CoV-2 virus itself and how much is a consequence of COVID-19 treatments is a topic of active discussion and research. Martin Hoenigl, MD, of the University of Graz, Austria, a leading researcher in medical mycology, said research shows corticosteroids and anti–IL-6 treatments, such as tocilizumab, used to treat COVID-19–driven acute respiratory failure clearly have contributed to CAPA. But he contends that “a number of other mechanisms” are involved as well.

Hoenigl_Martin_web.jpg

“The immunologic mechanisms are definitely different in these patients with viral illness than in other ICU patients [who develop aspergilliosis]. It’s not just the corticosteroids. The more we learn, we see the virus plays a role as well, suppressing the interferon pathway,” for example, said Dr. Hoenigl, associate professor in the division of infectious diseases and the European Confederation of Medical Mycology (ECMM) Center of Excellence at the university. The earliest reports of CAPA came “when ICUs weren’t using dexamethasone or tocilizumab,” he noted.

In a paper published recently in Lancet Respiratory Medicine that Dr. Hoenigl and others point to, Belgian researchers reported a “three-level breach” in innate antifungal immunity in both IAPA and CAPA, affecting the integrity of the epithelial barrier, the capacity to phagocytose and kill Aspergillus spores, and the ability to destroy Aspergillus hyphae, which is mainly mediated by neutrophils.

The researchers ran a host of genetic and protein analyses on lung samples (most collected via BAL) of 169 patients with influenza or COVID-19, with and without aspergillosis. They found that patients with CAPA had significantly lower neutrophil cell fractions than patients with COVID-19 only, and patients with IAPA or CAPA had reduced type II IFN signaling and increased concentrations of fibrosis-associated growth factors in the lower respiratory tracts (Lancet Respir Med. 2022 Aug 24).

Chiller_Tom_web.jpg

Tom Chiller, MD, MPH, chief of the Center for Disease Control and Prevention’s Mycotic Disease Branch, said he’s watching such research with interest. For now, he said, it’s important to also consider that “data on COVID show that almost all patients going into the ICUs with pneumonia and COVID are getting broad-spectrum antibiotics” in addition to corticosteroids.

By wiping out good bacteria, the antibiotics could be “creating a perfect niche for fungi to grow,” he said.


 

Diagnostic challenges

Aspergillus that has invaded the lung tissue in patients with COVID-19 appears to grow there for some time – around 8-10 days, much longer than in IAPA – before becoming angioinvasive, said Dr. Hoenigl. Such a pathophysiology “implicates that we should try to diagnose it while it’s in the lung tissue, using the BAL fluid, and not yet in the blood,” he said.

Some multicenter studies, including one from Europe on Aspergillus test profiles in critically ill COVID-19 patients, have shown mortality rates of close to 90% in patients with CAPA who have positive serum biomarkers, despite appropriate antifungal therapy. “If diagnosed while confined to the lung, however, mortality rates are more like 40%-50% with antifungal therapy,” Dr. Hoenigl said. (Cohort studies published thus far have fairly consistently reported mortality rates in patients with CAPA greater than 40%, he said.)

Bronchoscopy isn’t always pragmatic or possible, however, and is variably used. Some patients with severe COVID-19 may be too unstable for any invasive procedure, said Dr. Permpalung.

Dr. Permpalung looks for CAPA using serum (1-3) beta-D-glucan (BDG, a generic fungal test not specific to Aspergillus), serum galactomannan (GM, specific for Aspergillus), and respiratory cultures (sputum or endotracheal aspirate if intubated) as initial screening tests in the ICU. If there are concerns for CAPA – based on these tests and/or the clinical picture – “a thoughtful risk-benefit discussion is required to determine if patients would benefit from a bronchoscopy or if we should just start them on empiric antifungal therapy.”

Unfortunately, the sensitivity of serum GM is relatively low in CAPA – lower than with classic invasive aspergillosis in the nonviral setting, sources said. BDG, on the other hand, can be falsely positive in the setting of antimicrobials and within the ICU. And the utility of imaging for CAPA is limited. Both the clinical picture and radiological findings of CAPA have resembled those of severe COVID – with the caveat of cavitary lung lesions visible on imaging.

“Cavities or nodules are a highly suspicious finding that could indicate possible fungal infection,” said pulmonologist Amir A. Zeki, MD, MAS, professor of medicine at the University of California, Davis, and codirector of the UC Davis Asthma Network Clinic, who has cared for patients with CAPA.

Zeki_Amir_A_web.jpg

Cavitation has been described in only a proportion of patients with CAPA, however. So in patients not doing well, “your suspicion has to be raised if you’re not seeing cavities,” he said.

Early in the pandemic, when patients worsened or failed to progress on mechanical ventilation, clinicians at the University of California, Davis, quickly learned not to pin blame too quickly on COVID-19 alone. This remains good advice today, Dr. Zeki said.

“If you have a patient who’s not doing well on a ventilator, not getting better [over weeks], has to be reintubated, has infiltrates or lung nodules that are evolving, or certainly, if they have a cavity, you have to suspect fungal infection,” said Dr. Zeki, who also practices at the Veterans Affairs Medical Center in San Diego. “Think about it for those patients who just aren’t moving forward and are continuing to struggle. Have a high index of suspicion, and consult with your infectious disease colleagues.”

Empiric treatment is warranted in some cases if a patient is doing poorly and suspicion for fungal infection is high based on clinical, radiographic, and/or laboratory evidence, he said.

The CDC’s Dr. Chiller said that screening and diagnostic algorithms currently vary from institution to institution, and that diagnostic challenges likely dissuade clinicians from thinking about fungi. “Clinicians often don’t want to deal with fungi – they’re difficult to diagnose, the treatments are limited and can be toxic. But fungi get pushed back until it’s too late,” he said.

“Fungal diagnostics is an area we all need a lot more help with,” and new diagnostics are in the pipeline, he said. In the meantime, he said, “there are tools out there, and we just need to use them more, and improve how they’re used.”

While reported CAPA thus far has typically occurred in the setting of ICU care and mechanical ventilation, it’s not always the case, Dr. Permpalung said. Lung and other solid organ transplant (SOT) recipients with COVID-19 are developing CAPA and other invasive secondary invasive fungal infections despite not being intubated, he said.

Of 276 SOT recipients with COVID-19 who required inpatient treatment at Johns Hopkins University hospitals from the beginning of the pandemic to March 2022, 23 patients developed invasive fungal infections (13 CAPA). Only a fraction – 38 of the 276 – had been intubated, he said.
 

Mucormycosis resistance

After CAPA, candidiasis and COVID-19-associated mucormycosis (CAM) – most frequently, rhino-orbital-cerebral disease or pulmonary disease – have been the leading reported fungal coinfections in COVID-19, said Dr. Hoenigl, who described the incidence, timeline, risk factors, and pathogenesis of these infections in a review published this year in Nature Microbiology. .

In India, where there has long been high exposure to Mucorales spores and a greater burden of invasive fungal disease, the rate of mucormycosis doubled in 2021, with rhino-orbital-cerebral disease reported almost exclusively, he said. Pulmonary disease has occurred almost exclusively in the ICU setting and has been present in about 50% of cases outside of India, including Europe and the United States.

A preprint meta-analysis of CAM cases posted by the Lancet in July 2022, in which investigators analyzed individual data of 556 reported cases of COVID-19–associated CAM, shows diabetes and history of corticosteroid use present in most patients, and an overall mortality rate of 44.4%, most of which stems from cases of pulmonary or disseminated disease. Thirteen of the 556 reported cases were from the United States.

An important take-away from the analysis, Dr. Hoenigl said, is that Aspergillus coinfection was seen in 7% of patients and was associated with higher mortality. “It’s important to consider that coinfections [of Aspergillus and Mucorales] can exist,” Dr. Hoenigl said, noting that like CAPA, pulmonary CAM is likely underdiagnosed and underreported.

As with CAPA, the clinical and radiological features of pulmonary CAM largely overlap with those associated with COVID-19, and bronchoscopy plays a central role in definitive diagnosis. In the United States, a Mucorales PCR test for blood and BAL fluid is commercially available and used at some centers, Dr. Hoenigl said.

“Mucormycosis is always difficult to treat ... a lot of the treatments don’t work particularly well,” said Dr. Thompson. “With aspergillosis, we have better treatment options.”

Dr. Thompson worries, however, about treatment resistance becoming widespread. Resistance to azole antifungal agents “is already pretty widespread in northern Europe, particularly in the Netherlands and part of the U.K.” because of injudicious use of antifungals in agriculture, he said. “We’ve started to see a few cases [of azole-resistant aspergillosis in the United States] and know it will be more widespread soon.”

Treatment resistance is a focus of the new WHO fungal priority pathogens list – the first such report from the organization. Of the 19 fungi on the list, 4 were ranked as critical: Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, and Candida albicans. Like Dr. Thompson, Dr. Hoenigl contributed to the WHO report.

Dr. Hoenigl reported grant/research support from Astellas, Merck, F2G, Gilread, Pfizer, and Scynexis. Dr. Marr disclosed employment and equity in Pearl Diagnostics and Sfunga Therapeutics. Dr. Thompson, Dr. Permpalung, and Dr. Zeki reported that they have no relevant financial disclosures.
 

COVID-19 has lifted the lid on the risks of secondary pulmonary fungal infections in patients with severe respiratory viral illness – even previously immunocompetent individuals – and highlighted the importance of vigilant investigation to achieve early diagnoses, leading experts say.

Pulmonary_aspergillosis_web.jpg

Most fungi are not under surveillance in the United States, leaving experts without a national picture of the true burden of infection through the pandemic. However, a collection of published case series, cohort studies, and reviews from Europe, the United States, and throughout the world – mainly pre-Omicron – show that fungal disease has affected a significant portion of critically ill patients with COVID-19, with concerning excess mortality, these experts say.

COVID-associated pulmonary aspergillosis (CAPA) has been the predominant fungal coinfection in the United States and internationally. But COVID-associated mucormycosis (CAM) – the infection that surged in India in early 2021 – has also affected some patients in the United States, published data show. So have Pneumocystitis pneumonia, cryptococcosis, histoplasmosis, and Candida infections (which mainly affect the bloodstream and abdomen), say the experts who were interviewed.

Thompson_George_web.jpg

“We had predicted [a rise in] aspergillosis, but we saw more than we thought we’d see. Most fungal infections became more common with COVID-19,” said George Thompson, MD, professor of clinical medicine at the University of California, Davis, and cochair of the University of Alabama–based Mycoses Study Group Education Committee, a group of experts in medical mycology. Pneumocystitis, for instance, “has historically been associated with AIDS or different types of leukemia or lymphoma, and is not an infection we’ve typically seen in our otherwise healthy ICU patients,” he noted. “But we did see more of it [with COVID-19].”

More recently, with fewer patients during the Omicron phase in intensive care units with acute respiratory failure, the profile of fungal disease secondary to COVID-19 has changed. Increasing proportions of patients have traditional risk factors for aspergillosis, such as hematologic malignancies and longer-term, pre-COVID use of systemic corticosteroids – a change that makes the contribution of the viral illness harder to distinguish.

Moving forward, the lessons of the COVID era – the fungal risks to patients with serious viral infections and the persistence needed to diagnose aspergillosis and other pulmonary fungal infections using bronchoscopy and imperfect noninvasive tests – should be taken to heart, experts say.

“Fungal diseases are not rare. They’re just not diagnosed because no one thinks to look for them,” said Dr. Thompson, a contributor to a recently released World Health Organization report naming a “fungal priority pathogens” list.

“We’re going to continue to see [secondary fungal infections] with other respiratory viruses,” he said. And overall, given environmental and other changes, “we’re going to see more and more fungal disease in the patients we take care of.”


 

CAPA not a surprise

CAPA is “not an unfamiliar story” in the world of fungal disease, given a history of influenza-associated pulmonary aspergillosis (IAPA), said Kieren A. Marr, MD, MBA, adjunct professor of medicine and past director of the transplant and oncology infectious diseases program at Johns Hopkins University, Baltimore, who has long researched invasive fungal disease.

Marr_Kieran_web.jpg

European researchers, she said, have led the way in describing a high incidence of IAPA in patients admitted to ICUs with influenza. In a retrospective multicenter cohort study reported in 2018 by the Dutch-Belgian Mycosis Study group, for instance, almost 20% of 432 influenza patients admitted to the ICU, including patients who were otherwise healthy and not immunocompromised, had the diagnosis a median of 3 days after ICU admission. (Across other cohort studies, rates of IAPA have ranged from 7% to 30%.)

Mortality was significant: 51% of patients with influenza and invasive pulmonary aspergillosis died within 90 days, compared with 28% of patients with influenza and no invasive pulmonary aspergillosis.

Reports from Europe early in the pandemic indicated that CAPA was a similarly serious problem, prompting establishment at Johns Hopkins University of an aggressive screening program utilizing biomarker-based testing of blood and bronchoalveolar lavage (BAL) fluid. Of 396 mechanically ventilated COVID-19 patients admitted to Johns Hopkins University hospitals between March and August 2020, 39 met the institution’s criteria for CAPA, Dr. Marr and her colleagues reported this year in what might be the largest U.S. cohort study of CAPA published to date.

“We now know definitively that people with severe influenza and with severe COVID also have high risks for both invasive and airway disease caused by airborne fungi, most commonly aspergilliosis,” Dr. Marr said.

More recent unpublished analyses of patients from the start of the pandemic to June 2021 show persistent risk, said Nitipong Permpalung, MD, MPH, assistant professor in transplant and oncology infectious diseases at Johns Hopkins University and lead author of the cohort study. Among 832 patients with COVID-19 who were mechanically ventilated in Johns Hopkins University hospitals, 11.8% had CAPA, he said. (Also, 3.2% had invasive candidiasis, and 1.1% had other invasive fungal infections.)

Other sources said in interviews that these CAPA prevalence rates generally mirror reports from Europe, though some investigators in Europe have reported CAPA rates more toward 15%.

(The Mycoses Study Group recently collected data from its consortium of U.S. medical centers on the prevalence of CAPA, with funding support from the CDC, but at press time the data had not yet been released. Dr. Thompson said he suspected the prevalence will be lower than earlier papers have suggested, “but still will reflect a significant burden of disease.”)

Patients in the published Johns Hopkins University study who had CAPA were more likely than those with COVID-19 but no CAPA to have underlying pulmonary disease, liver disease, coagulopathy, solid tumors, multiple myeloma, and COVID-19–directed corticosteroids. And they had uniformly worse outcomes with regards to severity of illness and length of intubation.

How much of CAPA is driven by the SARS-CoV-2 virus itself and how much is a consequence of COVID-19 treatments is a topic of active discussion and research. Martin Hoenigl, MD, of the University of Graz, Austria, a leading researcher in medical mycology, said research shows corticosteroids and anti–IL-6 treatments, such as tocilizumab, used to treat COVID-19–driven acute respiratory failure clearly have contributed to CAPA. But he contends that “a number of other mechanisms” are involved as well.

Hoenigl_Martin_web.jpg

“The immunologic mechanisms are definitely different in these patients with viral illness than in other ICU patients [who develop aspergilliosis]. It’s not just the corticosteroids. The more we learn, we see the virus plays a role as well, suppressing the interferon pathway,” for example, said Dr. Hoenigl, associate professor in the division of infectious diseases and the European Confederation of Medical Mycology (ECMM) Center of Excellence at the university. The earliest reports of CAPA came “when ICUs weren’t using dexamethasone or tocilizumab,” he noted.

In a paper published recently in Lancet Respiratory Medicine that Dr. Hoenigl and others point to, Belgian researchers reported a “three-level breach” in innate antifungal immunity in both IAPA and CAPA, affecting the integrity of the epithelial barrier, the capacity to phagocytose and kill Aspergillus spores, and the ability to destroy Aspergillus hyphae, which is mainly mediated by neutrophils.

The researchers ran a host of genetic and protein analyses on lung samples (most collected via BAL) of 169 patients with influenza or COVID-19, with and without aspergillosis. They found that patients with CAPA had significantly lower neutrophil cell fractions than patients with COVID-19 only, and patients with IAPA or CAPA had reduced type II IFN signaling and increased concentrations of fibrosis-associated growth factors in the lower respiratory tracts (Lancet Respir Med. 2022 Aug 24).

Chiller_Tom_web.jpg

Tom Chiller, MD, MPH, chief of the Center for Disease Control and Prevention’s Mycotic Disease Branch, said he’s watching such research with interest. For now, he said, it’s important to also consider that “data on COVID show that almost all patients going into the ICUs with pneumonia and COVID are getting broad-spectrum antibiotics” in addition to corticosteroids.

By wiping out good bacteria, the antibiotics could be “creating a perfect niche for fungi to grow,” he said.


 

Diagnostic challenges

Aspergillus that has invaded the lung tissue in patients with COVID-19 appears to grow there for some time – around 8-10 days, much longer than in IAPA – before becoming angioinvasive, said Dr. Hoenigl. Such a pathophysiology “implicates that we should try to diagnose it while it’s in the lung tissue, using the BAL fluid, and not yet in the blood,” he said.

Some multicenter studies, including one from Europe on Aspergillus test profiles in critically ill COVID-19 patients, have shown mortality rates of close to 90% in patients with CAPA who have positive serum biomarkers, despite appropriate antifungal therapy. “If diagnosed while confined to the lung, however, mortality rates are more like 40%-50% with antifungal therapy,” Dr. Hoenigl said. (Cohort studies published thus far have fairly consistently reported mortality rates in patients with CAPA greater than 40%, he said.)

Bronchoscopy isn’t always pragmatic or possible, however, and is variably used. Some patients with severe COVID-19 may be too unstable for any invasive procedure, said Dr. Permpalung.

Dr. Permpalung looks for CAPA using serum (1-3) beta-D-glucan (BDG, a generic fungal test not specific to Aspergillus), serum galactomannan (GM, specific for Aspergillus), and respiratory cultures (sputum or endotracheal aspirate if intubated) as initial screening tests in the ICU. If there are concerns for CAPA – based on these tests and/or the clinical picture – “a thoughtful risk-benefit discussion is required to determine if patients would benefit from a bronchoscopy or if we should just start them on empiric antifungal therapy.”

Unfortunately, the sensitivity of serum GM is relatively low in CAPA – lower than with classic invasive aspergillosis in the nonviral setting, sources said. BDG, on the other hand, can be falsely positive in the setting of antimicrobials and within the ICU. And the utility of imaging for CAPA is limited. Both the clinical picture and radiological findings of CAPA have resembled those of severe COVID – with the caveat of cavitary lung lesions visible on imaging.

“Cavities or nodules are a highly suspicious finding that could indicate possible fungal infection,” said pulmonologist Amir A. Zeki, MD, MAS, professor of medicine at the University of California, Davis, and codirector of the UC Davis Asthma Network Clinic, who has cared for patients with CAPA.

Zeki_Amir_A_web.jpg

Cavitation has been described in only a proportion of patients with CAPA, however. So in patients not doing well, “your suspicion has to be raised if you’re not seeing cavities,” he said.

Early in the pandemic, when patients worsened or failed to progress on mechanical ventilation, clinicians at the University of California, Davis, quickly learned not to pin blame too quickly on COVID-19 alone. This remains good advice today, Dr. Zeki said.

“If you have a patient who’s not doing well on a ventilator, not getting better [over weeks], has to be reintubated, has infiltrates or lung nodules that are evolving, or certainly, if they have a cavity, you have to suspect fungal infection,” said Dr. Zeki, who also practices at the Veterans Affairs Medical Center in San Diego. “Think about it for those patients who just aren’t moving forward and are continuing to struggle. Have a high index of suspicion, and consult with your infectious disease colleagues.”

Empiric treatment is warranted in some cases if a patient is doing poorly and suspicion for fungal infection is high based on clinical, radiographic, and/or laboratory evidence, he said.

The CDC’s Dr. Chiller said that screening and diagnostic algorithms currently vary from institution to institution, and that diagnostic challenges likely dissuade clinicians from thinking about fungi. “Clinicians often don’t want to deal with fungi – they’re difficult to diagnose, the treatments are limited and can be toxic. But fungi get pushed back until it’s too late,” he said.

“Fungal diagnostics is an area we all need a lot more help with,” and new diagnostics are in the pipeline, he said. In the meantime, he said, “there are tools out there, and we just need to use them more, and improve how they’re used.”

While reported CAPA thus far has typically occurred in the setting of ICU care and mechanical ventilation, it’s not always the case, Dr. Permpalung said. Lung and other solid organ transplant (SOT) recipients with COVID-19 are developing CAPA and other invasive secondary invasive fungal infections despite not being intubated, he said.

Of 276 SOT recipients with COVID-19 who required inpatient treatment at Johns Hopkins University hospitals from the beginning of the pandemic to March 2022, 23 patients developed invasive fungal infections (13 CAPA). Only a fraction – 38 of the 276 – had been intubated, he said.
 

Mucormycosis resistance

After CAPA, candidiasis and COVID-19-associated mucormycosis (CAM) – most frequently, rhino-orbital-cerebral disease or pulmonary disease – have been the leading reported fungal coinfections in COVID-19, said Dr. Hoenigl, who described the incidence, timeline, risk factors, and pathogenesis of these infections in a review published this year in Nature Microbiology. .

In India, where there has long been high exposure to Mucorales spores and a greater burden of invasive fungal disease, the rate of mucormycosis doubled in 2021, with rhino-orbital-cerebral disease reported almost exclusively, he said. Pulmonary disease has occurred almost exclusively in the ICU setting and has been present in about 50% of cases outside of India, including Europe and the United States.

A preprint meta-analysis of CAM cases posted by the Lancet in July 2022, in which investigators analyzed individual data of 556 reported cases of COVID-19–associated CAM, shows diabetes and history of corticosteroid use present in most patients, and an overall mortality rate of 44.4%, most of which stems from cases of pulmonary or disseminated disease. Thirteen of the 556 reported cases were from the United States.

An important take-away from the analysis, Dr. Hoenigl said, is that Aspergillus coinfection was seen in 7% of patients and was associated with higher mortality. “It’s important to consider that coinfections [of Aspergillus and Mucorales] can exist,” Dr. Hoenigl said, noting that like CAPA, pulmonary CAM is likely underdiagnosed and underreported.

As with CAPA, the clinical and radiological features of pulmonary CAM largely overlap with those associated with COVID-19, and bronchoscopy plays a central role in definitive diagnosis. In the United States, a Mucorales PCR test for blood and BAL fluid is commercially available and used at some centers, Dr. Hoenigl said.

“Mucormycosis is always difficult to treat ... a lot of the treatments don’t work particularly well,” said Dr. Thompson. “With aspergillosis, we have better treatment options.”

Dr. Thompson worries, however, about treatment resistance becoming widespread. Resistance to azole antifungal agents “is already pretty widespread in northern Europe, particularly in the Netherlands and part of the U.K.” because of injudicious use of antifungals in agriculture, he said. “We’ve started to see a few cases [of azole-resistant aspergillosis in the United States] and know it will be more widespread soon.”

Treatment resistance is a focus of the new WHO fungal priority pathogens list – the first such report from the organization. Of the 19 fungi on the list, 4 were ranked as critical: Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, and Candida albicans. Like Dr. Thompson, Dr. Hoenigl contributed to the WHO report.

Dr. Hoenigl reported grant/research support from Astellas, Merck, F2G, Gilread, Pfizer, and Scynexis. Dr. Marr disclosed employment and equity in Pearl Diagnostics and Sfunga Therapeutics. Dr. Thompson, Dr. Permpalung, and Dr. Zeki reported that they have no relevant financial disclosures.
 

COVID-19 has lifted the lid on the risks of secondary pulmonary fungal infections in patients with severe respiratory viral illness – even previously immunocompetent individuals – and highlighted the importance of vigilant investigation to achieve early diagnoses, leading experts say.

Pulmonary_aspergillosis_web.jpg

Most fungi are not under surveillance in the United States, leaving experts without a national picture of the true burden of infection through the pandemic. However, a collection of published case series, cohort studies, and reviews from Europe, the United States, and throughout the world – mainly pre-Omicron – show that fungal disease has affected a significant portion of critically ill patients with COVID-19, with concerning excess mortality, these experts say.

COVID-associated pulmonary aspergillosis (CAPA) has been the predominant fungal coinfection in the United States and internationally. But COVID-associated mucormycosis (CAM) – the infection that surged in India in early 2021 – has also affected some patients in the United States, published data show. So have Pneumocystitis pneumonia, cryptococcosis, histoplasmosis, and Candida infections (which mainly affect the bloodstream and abdomen), say the experts who were interviewed.

Thompson_George_web.jpg

“We had predicted [a rise in] aspergillosis, but we saw more than we thought we’d see. Most fungal infections became more common with COVID-19,” said George Thompson, MD, professor of clinical medicine at the University of California, Davis, and cochair of the University of Alabama–based Mycoses Study Group Education Committee, a group of experts in medical mycology. Pneumocystitis, for instance, “has historically been associated with AIDS or different types of leukemia or lymphoma, and is not an infection we’ve typically seen in our otherwise healthy ICU patients,” he noted. “But we did see more of it [with COVID-19].”

More recently, with fewer patients during the Omicron phase in intensive care units with acute respiratory failure, the profile of fungal disease secondary to COVID-19 has changed. Increasing proportions of patients have traditional risk factors for aspergillosis, such as hematologic malignancies and longer-term, pre-COVID use of systemic corticosteroids – a change that makes the contribution of the viral illness harder to distinguish.

Moving forward, the lessons of the COVID era – the fungal risks to patients with serious viral infections and the persistence needed to diagnose aspergillosis and other pulmonary fungal infections using bronchoscopy and imperfect noninvasive tests – should be taken to heart, experts say.

“Fungal diseases are not rare. They’re just not diagnosed because no one thinks to look for them,” said Dr. Thompson, a contributor to a recently released World Health Organization report naming a “fungal priority pathogens” list.

“We’re going to continue to see [secondary fungal infections] with other respiratory viruses,” he said. And overall, given environmental and other changes, “we’re going to see more and more fungal disease in the patients we take care of.”


 

CAPA not a surprise

CAPA is “not an unfamiliar story” in the world of fungal disease, given a history of influenza-associated pulmonary aspergillosis (IAPA), said Kieren A. Marr, MD, MBA, adjunct professor of medicine and past director of the transplant and oncology infectious diseases program at Johns Hopkins University, Baltimore, who has long researched invasive fungal disease.

Marr_Kieran_web.jpg

European researchers, she said, have led the way in describing a high incidence of IAPA in patients admitted to ICUs with influenza. In a retrospective multicenter cohort study reported in 2018 by the Dutch-Belgian Mycosis Study group, for instance, almost 20% of 432 influenza patients admitted to the ICU, including patients who were otherwise healthy and not immunocompromised, had the diagnosis a median of 3 days after ICU admission. (Across other cohort studies, rates of IAPA have ranged from 7% to 30%.)

Mortality was significant: 51% of patients with influenza and invasive pulmonary aspergillosis died within 90 days, compared with 28% of patients with influenza and no invasive pulmonary aspergillosis.

Reports from Europe early in the pandemic indicated that CAPA was a similarly serious problem, prompting establishment at Johns Hopkins University of an aggressive screening program utilizing biomarker-based testing of blood and bronchoalveolar lavage (BAL) fluid. Of 396 mechanically ventilated COVID-19 patients admitted to Johns Hopkins University hospitals between March and August 2020, 39 met the institution’s criteria for CAPA, Dr. Marr and her colleagues reported this year in what might be the largest U.S. cohort study of CAPA published to date.

“We now know definitively that people with severe influenza and with severe COVID also have high risks for both invasive and airway disease caused by airborne fungi, most commonly aspergilliosis,” Dr. Marr said.

More recent unpublished analyses of patients from the start of the pandemic to June 2021 show persistent risk, said Nitipong Permpalung, MD, MPH, assistant professor in transplant and oncology infectious diseases at Johns Hopkins University and lead author of the cohort study. Among 832 patients with COVID-19 who were mechanically ventilated in Johns Hopkins University hospitals, 11.8% had CAPA, he said. (Also, 3.2% had invasive candidiasis, and 1.1% had other invasive fungal infections.)

Other sources said in interviews that these CAPA prevalence rates generally mirror reports from Europe, though some investigators in Europe have reported CAPA rates more toward 15%.

(The Mycoses Study Group recently collected data from its consortium of U.S. medical centers on the prevalence of CAPA, with funding support from the CDC, but at press time the data had not yet been released. Dr. Thompson said he suspected the prevalence will be lower than earlier papers have suggested, “but still will reflect a significant burden of disease.”)

Patients in the published Johns Hopkins University study who had CAPA were more likely than those with COVID-19 but no CAPA to have underlying pulmonary disease, liver disease, coagulopathy, solid tumors, multiple myeloma, and COVID-19–directed corticosteroids. And they had uniformly worse outcomes with regards to severity of illness and length of intubation.

How much of CAPA is driven by the SARS-CoV-2 virus itself and how much is a consequence of COVID-19 treatments is a topic of active discussion and research. Martin Hoenigl, MD, of the University of Graz, Austria, a leading researcher in medical mycology, said research shows corticosteroids and anti–IL-6 treatments, such as tocilizumab, used to treat COVID-19–driven acute respiratory failure clearly have contributed to CAPA. But he contends that “a number of other mechanisms” are involved as well.

Hoenigl_Martin_web.jpg

“The immunologic mechanisms are definitely different in these patients with viral illness than in other ICU patients [who develop aspergilliosis]. It’s not just the corticosteroids. The more we learn, we see the virus plays a role as well, suppressing the interferon pathway,” for example, said Dr. Hoenigl, associate professor in the division of infectious diseases and the European Confederation of Medical Mycology (ECMM) Center of Excellence at the university. The earliest reports of CAPA came “when ICUs weren’t using dexamethasone or tocilizumab,” he noted.

In a paper published recently in Lancet Respiratory Medicine that Dr. Hoenigl and others point to, Belgian researchers reported a “three-level breach” in innate antifungal immunity in both IAPA and CAPA, affecting the integrity of the epithelial barrier, the capacity to phagocytose and kill Aspergillus spores, and the ability to destroy Aspergillus hyphae, which is mainly mediated by neutrophils.

The researchers ran a host of genetic and protein analyses on lung samples (most collected via BAL) of 169 patients with influenza or COVID-19, with and without aspergillosis. They found that patients with CAPA had significantly lower neutrophil cell fractions than patients with COVID-19 only, and patients with IAPA or CAPA had reduced type II IFN signaling and increased concentrations of fibrosis-associated growth factors in the lower respiratory tracts (Lancet Respir Med. 2022 Aug 24).

Chiller_Tom_web.jpg

Tom Chiller, MD, MPH, chief of the Center for Disease Control and Prevention’s Mycotic Disease Branch, said he’s watching such research with interest. For now, he said, it’s important to also consider that “data on COVID show that almost all patients going into the ICUs with pneumonia and COVID are getting broad-spectrum antibiotics” in addition to corticosteroids.

By wiping out good bacteria, the antibiotics could be “creating a perfect niche for fungi to grow,” he said.


 

Diagnostic challenges

Aspergillus that has invaded the lung tissue in patients with COVID-19 appears to grow there for some time – around 8-10 days, much longer than in IAPA – before becoming angioinvasive, said Dr. Hoenigl. Such a pathophysiology “implicates that we should try to diagnose it while it’s in the lung tissue, using the BAL fluid, and not yet in the blood,” he said.

Some multicenter studies, including one from Europe on Aspergillus test profiles in critically ill COVID-19 patients, have shown mortality rates of close to 90% in patients with CAPA who have positive serum biomarkers, despite appropriate antifungal therapy. “If diagnosed while confined to the lung, however, mortality rates are more like 40%-50% with antifungal therapy,” Dr. Hoenigl said. (Cohort studies published thus far have fairly consistently reported mortality rates in patients with CAPA greater than 40%, he said.)

Bronchoscopy isn’t always pragmatic or possible, however, and is variably used. Some patients with severe COVID-19 may be too unstable for any invasive procedure, said Dr. Permpalung.

Dr. Permpalung looks for CAPA using serum (1-3) beta-D-glucan (BDG, a generic fungal test not specific to Aspergillus), serum galactomannan (GM, specific for Aspergillus), and respiratory cultures (sputum or endotracheal aspirate if intubated) as initial screening tests in the ICU. If there are concerns for CAPA – based on these tests and/or the clinical picture – “a thoughtful risk-benefit discussion is required to determine if patients would benefit from a bronchoscopy or if we should just start them on empiric antifungal therapy.”

Unfortunately, the sensitivity of serum GM is relatively low in CAPA – lower than with classic invasive aspergillosis in the nonviral setting, sources said. BDG, on the other hand, can be falsely positive in the setting of antimicrobials and within the ICU. And the utility of imaging for CAPA is limited. Both the clinical picture and radiological findings of CAPA have resembled those of severe COVID – with the caveat of cavitary lung lesions visible on imaging.

“Cavities or nodules are a highly suspicious finding that could indicate possible fungal infection,” said pulmonologist Amir A. Zeki, MD, MAS, professor of medicine at the University of California, Davis, and codirector of the UC Davis Asthma Network Clinic, who has cared for patients with CAPA.

Zeki_Amir_A_web.jpg

Cavitation has been described in only a proportion of patients with CAPA, however. So in patients not doing well, “your suspicion has to be raised if you’re not seeing cavities,” he said.

Early in the pandemic, when patients worsened or failed to progress on mechanical ventilation, clinicians at the University of California, Davis, quickly learned not to pin blame too quickly on COVID-19 alone. This remains good advice today, Dr. Zeki said.

“If you have a patient who’s not doing well on a ventilator, not getting better [over weeks], has to be reintubated, has infiltrates or lung nodules that are evolving, or certainly, if they have a cavity, you have to suspect fungal infection,” said Dr. Zeki, who also practices at the Veterans Affairs Medical Center in San Diego. “Think about it for those patients who just aren’t moving forward and are continuing to struggle. Have a high index of suspicion, and consult with your infectious disease colleagues.”

Empiric treatment is warranted in some cases if a patient is doing poorly and suspicion for fungal infection is high based on clinical, radiographic, and/or laboratory evidence, he said.

The CDC’s Dr. Chiller said that screening and diagnostic algorithms currently vary from institution to institution, and that diagnostic challenges likely dissuade clinicians from thinking about fungi. “Clinicians often don’t want to deal with fungi – they’re difficult to diagnose, the treatments are limited and can be toxic. But fungi get pushed back until it’s too late,” he said.

“Fungal diagnostics is an area we all need a lot more help with,” and new diagnostics are in the pipeline, he said. In the meantime, he said, “there are tools out there, and we just need to use them more, and improve how they’re used.”

While reported CAPA thus far has typically occurred in the setting of ICU care and mechanical ventilation, it’s not always the case, Dr. Permpalung said. Lung and other solid organ transplant (SOT) recipients with COVID-19 are developing CAPA and other invasive secondary invasive fungal infections despite not being intubated, he said.

Of 276 SOT recipients with COVID-19 who required inpatient treatment at Johns Hopkins University hospitals from the beginning of the pandemic to March 2022, 23 patients developed invasive fungal infections (13 CAPA). Only a fraction – 38 of the 276 – had been intubated, he said.
 

Mucormycosis resistance

After CAPA, candidiasis and COVID-19-associated mucormycosis (CAM) – most frequently, rhino-orbital-cerebral disease or pulmonary disease – have been the leading reported fungal coinfections in COVID-19, said Dr. Hoenigl, who described the incidence, timeline, risk factors, and pathogenesis of these infections in a review published this year in Nature Microbiology. .

In India, where there has long been high exposure to Mucorales spores and a greater burden of invasive fungal disease, the rate of mucormycosis doubled in 2021, with rhino-orbital-cerebral disease reported almost exclusively, he said. Pulmonary disease has occurred almost exclusively in the ICU setting and has been present in about 50% of cases outside of India, including Europe and the United States.

A preprint meta-analysis of CAM cases posted by the Lancet in July 2022, in which investigators analyzed individual data of 556 reported cases of COVID-19–associated CAM, shows diabetes and history of corticosteroid use present in most patients, and an overall mortality rate of 44.4%, most of which stems from cases of pulmonary or disseminated disease. Thirteen of the 556 reported cases were from the United States.

An important take-away from the analysis, Dr. Hoenigl said, is that Aspergillus coinfection was seen in 7% of patients and was associated with higher mortality. “It’s important to consider that coinfections [of Aspergillus and Mucorales] can exist,” Dr. Hoenigl said, noting that like CAPA, pulmonary CAM is likely underdiagnosed and underreported.

As with CAPA, the clinical and radiological features of pulmonary CAM largely overlap with those associated with COVID-19, and bronchoscopy plays a central role in definitive diagnosis. In the United States, a Mucorales PCR test for blood and BAL fluid is commercially available and used at some centers, Dr. Hoenigl said.

“Mucormycosis is always difficult to treat ... a lot of the treatments don’t work particularly well,” said Dr. Thompson. “With aspergillosis, we have better treatment options.”

Dr. Thompson worries, however, about treatment resistance becoming widespread. Resistance to azole antifungal agents “is already pretty widespread in northern Europe, particularly in the Netherlands and part of the U.K.” because of injudicious use of antifungals in agriculture, he said. “We’ve started to see a few cases [of azole-resistant aspergillosis in the United States] and know it will be more widespread soon.”

Treatment resistance is a focus of the new WHO fungal priority pathogens list – the first such report from the organization. Of the 19 fungi on the list, 4 were ranked as critical: Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, and Candida albicans. Like Dr. Thompson, Dr. Hoenigl contributed to the WHO report.

Dr. Hoenigl reported grant/research support from Astellas, Merck, F2G, Gilread, Pfizer, and Scynexis. Dr. Marr disclosed employment and equity in Pearl Diagnostics and Sfunga Therapeutics. Dr. Thompson, Dr. Permpalung, and Dr. Zeki reported that they have no relevant financial disclosures.
 

BUENOS AIRES – Emerging invasive fungal infections represent a new diagnostic and therapeutic challenge. To address their growing clinical impact on immunocompromised patients requires better local epidemiologic records, said a specialist at the XXII Congress of the Argentine Society of Infectology.
 

“To know that these fungal infections exist, we need epidemiologists, doctors, and microbiologists to join in constant and ongoing multidisciplinary work to generate the necessary databases and to know the pathologies that we have. I believe that in this respect we are falling short,” said Javier Afeltra, PhD, a mycologist at the Ramos Mejía Hospital in Buenos Aires, professor of microbiology at the School of Medicine of the University of Buenos Aires, and coordinator of the commission of immunocompromised patients of the Argentine Society of Infectious Diseases.

“There is some change in mentality that encourages professionals to report the cases they detect – for example, in scientific meetings,” Dr. Afeltra told this news orgnization. “But the problem is that there is no unified registry.

“That’s what we lack: a place to record all those isolated cases. Records where clinical and microbiological data are together within a click. Perhaps the microbiologists report their findings to the Malbrán Institute, an Argentine reference center for infectious disease research, but we do not know what the patients had. And we doctors may get together to make records of what happens clinically with the patient, but the germ data are elsewhere. We need a common registry,” he stressed.

“The main importance of a registry of this type is that it would allow a diagnostic and therapeutic decision to be made that is appropriate to the epidemiological profile of the country and the region, not looking at what they do in the North. Most likely, the best antifungal treatment for our country differs from what is indicated in the guidelines written elsewhere,” said Dr. Afeltra.

Dr. Afeltra pointed out that in the United States, when an oncohematology patient does not respond to antimicrobial treatment, the first thing that doctors think is that the patient has aspergillosis or mucormycosis, in which the fungal infection is caused by filamentous fungi.

But an analysis of data from the REMINI registry – the only prospective, observational, multicenter surveillance registry for invasive mycoses in immunocompromised patients (excluding HIV infection) in Argentina, which has been in existence since 2010 – tells a different story. The most prevalent fungal infections turned out to be those caused by Aspergillus species, followed by Fusarium species. Together, they account for more than half of cases. Mucoral infections (mucormycosis) account for less than 6%. And the initial treatments for these diseases could be different.

Changes in the local epidemiology can occur because the behavior of phytopathogenic fungi found in the environment can be modified. For example, cases of chronic mucormycosis can be detected in China but are virtually nonexistent on this side of the Greenwich meridian, Dr. Afeltra said.

“Nature is not the same in geographical areas, and the fungi … we breathe are completely different, so patients have different infections and require different diagnostic and treatment approaches,” he stressed.

Dr. Afeltra mentioned different fungi that are emerging locally and globally, including yeasts, septate, dimorphic, and pigmented hyaline fungi, that have a variable response to antifungal drugs and are associated with high mortality, “which has a lot to do with a later diagnosis,” he said, noting that reports have increased worldwide. A barrier to sharing this information more widely with the professional community, in addition to the lack of records, is the difficulty in publishing cases or series of cases in indexed journals.

Another challenge in characterizing the phenomenon is in regard to taxonomic reclassifications of fungi. Such reclassifications can mean that “perhaps we are speaking of the same pathogen in similar situations, believing that we are referring to different pathogens,” said Dr. Afeltra.
 

Clinical pearls related to emerging fungal pathogens

Candida auris. This organism has emerged simultaneously on several continents. It has pathogenicity factors typical of the genus, such as biofilm formation and production of phospholipases and proteinases, although it has greater thermal tolerance. In hospitals, it colonizes for weeks and months. In Argentina, it is resistant to multiple antifungal agents. Sensitivity is variable in different geographical regions. Most strains are resistant to fluconazole, and there is variable resistance to the other triazoles [which are not normally used to treat candidemia]. In the United States, in vitro resistance to amphotericin B is up to 30%, and resistance to echinocandins is up to 5%. New drugs such as rezafungin and ibrexafungerp are being studied. Infection control is similar to that used to control Clostridium difficile.

Fusarium. This genus affects immunocompromised patients, including transplant recipients of solid organs and hematopoietic progenitor cells and patients with neutropenia. The genus has various species, included within complexes, such as F. solani SC, F. oxysporum SC, and F. fujikuroi SC, with clinical manifestations similar to those of aspergillosis. In addition to the pulmonary and disseminated forms, there may be skin involvement attributable to dissemination from a respiratory focus or by contiguity from a focus of onychomycosis. In general, mortality is high, and responses to antifungal agents are variable. Some species are more sensitive to voriconazole or posaconazole, and others less so. All show in vitro resistance to itraconazole. In Argentina, voriconazole is usually used as initial treatment, and in special cases, liposomal amphotericin B or combinations. Fosmanogepix is being evaluated for the future.

Azole-resistant aspergillosis. This infection has shown resistance to itraconazole and third-generation azole drugs. In immunocompromised patients, mortlaity is high. Early detection is key. It is sensitive to amphotericin B and echinocandins. It is generally treated with liposomal amphotericin B. Olorofim and fosmanogepix are being studied.

Pulmonary aspergillosis associated with COVID-19. This infection is associated with high mortality among intubated patients. Signs and symptoms include fever, pleural effusion, hemoptysis, and chest pain, with infiltrates or cavitations on imaging. Determining the diagnosis is difficult. “We couldn’t perform lung biopsies, and it was difficult for us to get patients out of intensive care units for CT scans. We treated the proven cases. We treated the probable cases, and those that had a very low certainty of disease were also treated. We came across this emergency and tried to do the best we could,” said Dr. Afeltra. A digital readout lateral flow trial (Sona Aspergillus Galactomannan LFA) for the quantification of galactomannan, a cell wall component of the Aspergillus genus, proved to be a useful tool for screening and diagnosing patients with probable pulmonary aspergillosis associated with COVID-19. The incidence of invasive mycosis was around 10% among 185 seriously ill COVID-19 patients, according to an Argentine multicenter prospective study in which Dr. Afeltra participated.

Scedosporium and Lomentospora. These genera are rarer septate hyaline fungi. Scedosporium is a complex of species. One species, S. apiospermum, can colonize pediatric patients with cystic fibrosis. Lomentospora prolificans is a multiresistant fungus. It produces pulmonary compromise or disseminated infection. The response to antifungal agents is variable, with a high minimum inhibitory concentration for amphotericin B and isavuconazole. Patients are usually treated with voriconazole alone or in combination with terbinafine or micafungin. Olorofim is emerging as a promising treatment.

Dr. Afeltra has received fees from Biotoscana, Gador, Pfizer, Merck, and Sandoz.

This article was translated from the Medscape Spanish edition, a version appeared on Medscape.com.

BUENOS AIRES – Emerging invasive fungal infections represent a new diagnostic and therapeutic challenge. To address their growing clinical impact on immunocompromised patients requires better local epidemiologic records, said a specialist at the XXII Congress of the Argentine Society of Infectology.
 

“To know that these fungal infections exist, we need epidemiologists, doctors, and microbiologists to join in constant and ongoing multidisciplinary work to generate the necessary databases and to know the pathologies that we have. I believe that in this respect we are falling short,” said Javier Afeltra, PhD, a mycologist at the Ramos Mejía Hospital in Buenos Aires, professor of microbiology at the School of Medicine of the University of Buenos Aires, and coordinator of the commission of immunocompromised patients of the Argentine Society of Infectious Diseases.

“There is some change in mentality that encourages professionals to report the cases they detect – for example, in scientific meetings,” Dr. Afeltra told this news orgnization. “But the problem is that there is no unified registry.

“That’s what we lack: a place to record all those isolated cases. Records where clinical and microbiological data are together within a click. Perhaps the microbiologists report their findings to the Malbrán Institute, an Argentine reference center for infectious disease research, but we do not know what the patients had. And we doctors may get together to make records of what happens clinically with the patient, but the germ data are elsewhere. We need a common registry,” he stressed.

“The main importance of a registry of this type is that it would allow a diagnostic and therapeutic decision to be made that is appropriate to the epidemiological profile of the country and the region, not looking at what they do in the North. Most likely, the best antifungal treatment for our country differs from what is indicated in the guidelines written elsewhere,” said Dr. Afeltra.

Dr. Afeltra pointed out that in the United States, when an oncohematology patient does not respond to antimicrobial treatment, the first thing that doctors think is that the patient has aspergillosis or mucormycosis, in which the fungal infection is caused by filamentous fungi.

But an analysis of data from the REMINI registry – the only prospective, observational, multicenter surveillance registry for invasive mycoses in immunocompromised patients (excluding HIV infection) in Argentina, which has been in existence since 2010 – tells a different story. The most prevalent fungal infections turned out to be those caused by Aspergillus species, followed by Fusarium species. Together, they account for more than half of cases. Mucoral infections (mucormycosis) account for less than 6%. And the initial treatments for these diseases could be different.

Changes in the local epidemiology can occur because the behavior of phytopathogenic fungi found in the environment can be modified. For example, cases of chronic mucormycosis can be detected in China but are virtually nonexistent on this side of the Greenwich meridian, Dr. Afeltra said.

“Nature is not the same in geographical areas, and the fungi … we breathe are completely different, so patients have different infections and require different diagnostic and treatment approaches,” he stressed.

Dr. Afeltra mentioned different fungi that are emerging locally and globally, including yeasts, septate, dimorphic, and pigmented hyaline fungi, that have a variable response to antifungal drugs and are associated with high mortality, “which has a lot to do with a later diagnosis,” he said, noting that reports have increased worldwide. A barrier to sharing this information more widely with the professional community, in addition to the lack of records, is the difficulty in publishing cases or series of cases in indexed journals.

Another challenge in characterizing the phenomenon is in regard to taxonomic reclassifications of fungi. Such reclassifications can mean that “perhaps we are speaking of the same pathogen in similar situations, believing that we are referring to different pathogens,” said Dr. Afeltra.
 

Clinical pearls related to emerging fungal pathogens

Candida auris. This organism has emerged simultaneously on several continents. It has pathogenicity factors typical of the genus, such as biofilm formation and production of phospholipases and proteinases, although it has greater thermal tolerance. In hospitals, it colonizes for weeks and months. In Argentina, it is resistant to multiple antifungal agents. Sensitivity is variable in different geographical regions. Most strains are resistant to fluconazole, and there is variable resistance to the other triazoles [which are not normally used to treat candidemia]. In the United States, in vitro resistance to amphotericin B is up to 30%, and resistance to echinocandins is up to 5%. New drugs such as rezafungin and ibrexafungerp are being studied. Infection control is similar to that used to control Clostridium difficile.

Fusarium. This genus affects immunocompromised patients, including transplant recipients of solid organs and hematopoietic progenitor cells and patients with neutropenia. The genus has various species, included within complexes, such as F. solani SC, F. oxysporum SC, and F. fujikuroi SC, with clinical manifestations similar to those of aspergillosis. In addition to the pulmonary and disseminated forms, there may be skin involvement attributable to dissemination from a respiratory focus or by contiguity from a focus of onychomycosis. In general, mortality is high, and responses to antifungal agents are variable. Some species are more sensitive to voriconazole or posaconazole, and others less so. All show in vitro resistance to itraconazole. In Argentina, voriconazole is usually used as initial treatment, and in special cases, liposomal amphotericin B or combinations. Fosmanogepix is being evaluated for the future.

Azole-resistant aspergillosis. This infection has shown resistance to itraconazole and third-generation azole drugs. In immunocompromised patients, mortlaity is high. Early detection is key. It is sensitive to amphotericin B and echinocandins. It is generally treated with liposomal amphotericin B. Olorofim and fosmanogepix are being studied.

Pulmonary aspergillosis associated with COVID-19. This infection is associated with high mortality among intubated patients. Signs and symptoms include fever, pleural effusion, hemoptysis, and chest pain, with infiltrates or cavitations on imaging. Determining the diagnosis is difficult. “We couldn’t perform lung biopsies, and it was difficult for us to get patients out of intensive care units for CT scans. We treated the proven cases. We treated the probable cases, and those that had a very low certainty of disease were also treated. We came across this emergency and tried to do the best we could,” said Dr. Afeltra. A digital readout lateral flow trial (Sona Aspergillus Galactomannan LFA) for the quantification of galactomannan, a cell wall component of the Aspergillus genus, proved to be a useful tool for screening and diagnosing patients with probable pulmonary aspergillosis associated with COVID-19. The incidence of invasive mycosis was around 10% among 185 seriously ill COVID-19 patients, according to an Argentine multicenter prospective study in which Dr. Afeltra participated.

Scedosporium and Lomentospora. These genera are rarer septate hyaline fungi. Scedosporium is a complex of species. One species, S. apiospermum, can colonize pediatric patients with cystic fibrosis. Lomentospora prolificans is a multiresistant fungus. It produces pulmonary compromise or disseminated infection. The response to antifungal agents is variable, with a high minimum inhibitory concentration for amphotericin B and isavuconazole. Patients are usually treated with voriconazole alone or in combination with terbinafine or micafungin. Olorofim is emerging as a promising treatment.

Dr. Afeltra has received fees from Biotoscana, Gador, Pfizer, Merck, and Sandoz.

This article was translated from the Medscape Spanish edition, a version appeared on Medscape.com.

BUENOS AIRES – Emerging invasive fungal infections represent a new diagnostic and therapeutic challenge. To address their growing clinical impact on immunocompromised patients requires better local epidemiologic records, said a specialist at the XXII Congress of the Argentine Society of Infectology.
 

“To know that these fungal infections exist, we need epidemiologists, doctors, and microbiologists to join in constant and ongoing multidisciplinary work to generate the necessary databases and to know the pathologies that we have. I believe that in this respect we are falling short,” said Javier Afeltra, PhD, a mycologist at the Ramos Mejía Hospital in Buenos Aires, professor of microbiology at the School of Medicine of the University of Buenos Aires, and coordinator of the commission of immunocompromised patients of the Argentine Society of Infectious Diseases.

“There is some change in mentality that encourages professionals to report the cases they detect – for example, in scientific meetings,” Dr. Afeltra told this news orgnization. “But the problem is that there is no unified registry.

“That’s what we lack: a place to record all those isolated cases. Records where clinical and microbiological data are together within a click. Perhaps the microbiologists report their findings to the Malbrán Institute, an Argentine reference center for infectious disease research, but we do not know what the patients had. And we doctors may get together to make records of what happens clinically with the patient, but the germ data are elsewhere. We need a common registry,” he stressed.

“The main importance of a registry of this type is that it would allow a diagnostic and therapeutic decision to be made that is appropriate to the epidemiological profile of the country and the region, not looking at what they do in the North. Most likely, the best antifungal treatment for our country differs from what is indicated in the guidelines written elsewhere,” said Dr. Afeltra.

Dr. Afeltra pointed out that in the United States, when an oncohematology patient does not respond to antimicrobial treatment, the first thing that doctors think is that the patient has aspergillosis or mucormycosis, in which the fungal infection is caused by filamentous fungi.

But an analysis of data from the REMINI registry – the only prospective, observational, multicenter surveillance registry for invasive mycoses in immunocompromised patients (excluding HIV infection) in Argentina, which has been in existence since 2010 – tells a different story. The most prevalent fungal infections turned out to be those caused by Aspergillus species, followed by Fusarium species. Together, they account for more than half of cases. Mucoral infections (mucormycosis) account for less than 6%. And the initial treatments for these diseases could be different.

Changes in the local epidemiology can occur because the behavior of phytopathogenic fungi found in the environment can be modified. For example, cases of chronic mucormycosis can be detected in China but are virtually nonexistent on this side of the Greenwich meridian, Dr. Afeltra said.

“Nature is not the same in geographical areas, and the fungi … we breathe are completely different, so patients have different infections and require different diagnostic and treatment approaches,” he stressed.

Dr. Afeltra mentioned different fungi that are emerging locally and globally, including yeasts, septate, dimorphic, and pigmented hyaline fungi, that have a variable response to antifungal drugs and are associated with high mortality, “which has a lot to do with a later diagnosis,” he said, noting that reports have increased worldwide. A barrier to sharing this information more widely with the professional community, in addition to the lack of records, is the difficulty in publishing cases or series of cases in indexed journals.

Another challenge in characterizing the phenomenon is in regard to taxonomic reclassifications of fungi. Such reclassifications can mean that “perhaps we are speaking of the same pathogen in similar situations, believing that we are referring to different pathogens,” said Dr. Afeltra.
 

Clinical pearls related to emerging fungal pathogens

Candida auris. This organism has emerged simultaneously on several continents. It has pathogenicity factors typical of the genus, such as biofilm formation and production of phospholipases and proteinases, although it has greater thermal tolerance. In hospitals, it colonizes for weeks and months. In Argentina, it is resistant to multiple antifungal agents. Sensitivity is variable in different geographical regions. Most strains are resistant to fluconazole, and there is variable resistance to the other triazoles [which are not normally used to treat candidemia]. In the United States, in vitro resistance to amphotericin B is up to 30%, and resistance to echinocandins is up to 5%. New drugs such as rezafungin and ibrexafungerp are being studied. Infection control is similar to that used to control Clostridium difficile.

Fusarium. This genus affects immunocompromised patients, including transplant recipients of solid organs and hematopoietic progenitor cells and patients with neutropenia. The genus has various species, included within complexes, such as F. solani SC, F. oxysporum SC, and F. fujikuroi SC, with clinical manifestations similar to those of aspergillosis. In addition to the pulmonary and disseminated forms, there may be skin involvement attributable to dissemination from a respiratory focus or by contiguity from a focus of onychomycosis. In general, mortality is high, and responses to antifungal agents are variable. Some species are more sensitive to voriconazole or posaconazole, and others less so. All show in vitro resistance to itraconazole. In Argentina, voriconazole is usually used as initial treatment, and in special cases, liposomal amphotericin B or combinations. Fosmanogepix is being evaluated for the future.

Azole-resistant aspergillosis. This infection has shown resistance to itraconazole and third-generation azole drugs. In immunocompromised patients, mortlaity is high. Early detection is key. It is sensitive to amphotericin B and echinocandins. It is generally treated with liposomal amphotericin B. Olorofim and fosmanogepix are being studied.

Pulmonary aspergillosis associated with COVID-19. This infection is associated with high mortality among intubated patients. Signs and symptoms include fever, pleural effusion, hemoptysis, and chest pain, with infiltrates or cavitations on imaging. Determining the diagnosis is difficult. “We couldn’t perform lung biopsies, and it was difficult for us to get patients out of intensive care units for CT scans. We treated the proven cases. We treated the probable cases, and those that had a very low certainty of disease were also treated. We came across this emergency and tried to do the best we could,” said Dr. Afeltra. A digital readout lateral flow trial (Sona Aspergillus Galactomannan LFA) for the quantification of galactomannan, a cell wall component of the Aspergillus genus, proved to be a useful tool for screening and diagnosing patients with probable pulmonary aspergillosis associated with COVID-19. The incidence of invasive mycosis was around 10% among 185 seriously ill COVID-19 patients, according to an Argentine multicenter prospective study in which Dr. Afeltra participated.

Scedosporium and Lomentospora. These genera are rarer septate hyaline fungi. Scedosporium is a complex of species. One species, S. apiospermum, can colonize pediatric patients with cystic fibrosis. Lomentospora prolificans is a multiresistant fungus. It produces pulmonary compromise or disseminated infection. The response to antifungal agents is variable, with a high minimum inhibitory concentration for amphotericin B and isavuconazole. Patients are usually treated with voriconazole alone or in combination with terbinafine or micafungin. Olorofim is emerging as a promising treatment.

Dr. Afeltra has received fees from Biotoscana, Gador, Pfizer, Merck, and Sandoz.

This article was translated from the Medscape Spanish edition, a version appeared on Medscape.com.

The Food and Drug Administration has approved oteseconazole capsules (Vivjoa), an azole antifungal agent, for the prevention of recurrent yeast infections in women who are not of reproductive potential.

Oteseconazole inhibits CYP51, an enzyme fungi require to preserve the integrity of their cell walls and to grow properly, according to Mycovia, the drug’s manufacturer. It is the first FDA-approved product for the treatment of recurrent vulvovaginal candidiasis (RVVC).

Recurrent vulvovaginal candidiasis, or chronic yeast infection, affects an estimated 138 million women worldwide annually. The condition is defined as three or more symptomatic acute episodes of yeast infection within a 12-month period. The primary symptoms of RVVC include vaginal itching, burning, irritation, and inflammation. Some patients may also experience abnormal vaginal discharge and pain during sex or urination.

“A medicine with Vivjoa’s sustained efficacy combined with the clinical safety profile has been long needed, as until now, physicians and their patients have had no FDA-approved medications for RVVC,” Stephen Brand, PhD, chief development officer of Mycovia, said in a statement. “We are excited to be the first to offer a medication designed specifically for RVVC, a challenging and chronic condition that is expected to increase in prevalence over the next decade.”

Approval for oteseconazole was based on results of three phase 3 trials involving 875 patients at 232 sites across 11 countries. In the U.S.-only ultraVIOLET trial, 89.7% of women with RVVC who received oteseconazole cleared their initial yeast infection and did not experience a recurrence during the 50-week maintenance period, compared with 57.1% of those who received fluconazole (Diflucan) followed by placebo (P < .001), according to Mycovia.

The most common side effects reported in phase 3 clinical studies were headache (7.4%) and nausea (3.6%), the company said. Patients with a hypersensitivity to oteseconazole should not take the drug, nor should those who are of reproductive potential, pregnant, or lactating.

Mycovia said it plans to launch the drug in the second quarter of 2022.

Full prescribing information is available online.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved oteseconazole capsules (Vivjoa), an azole antifungal agent, for the prevention of recurrent yeast infections in women who are not of reproductive potential.

Oteseconazole inhibits CYP51, an enzyme fungi require to preserve the integrity of their cell walls and to grow properly, according to Mycovia, the drug’s manufacturer. It is the first FDA-approved product for the treatment of recurrent vulvovaginal candidiasis (RVVC).

Recurrent vulvovaginal candidiasis, or chronic yeast infection, affects an estimated 138 million women worldwide annually. The condition is defined as three or more symptomatic acute episodes of yeast infection within a 12-month period. The primary symptoms of RVVC include vaginal itching, burning, irritation, and inflammation. Some patients may also experience abnormal vaginal discharge and pain during sex or urination.

“A medicine with Vivjoa’s sustained efficacy combined with the clinical safety profile has been long needed, as until now, physicians and their patients have had no FDA-approved medications for RVVC,” Stephen Brand, PhD, chief development officer of Mycovia, said in a statement. “We are excited to be the first to offer a medication designed specifically for RVVC, a challenging and chronic condition that is expected to increase in prevalence over the next decade.”

Approval for oteseconazole was based on results of three phase 3 trials involving 875 patients at 232 sites across 11 countries. In the U.S.-only ultraVIOLET trial, 89.7% of women with RVVC who received oteseconazole cleared their initial yeast infection and did not experience a recurrence during the 50-week maintenance period, compared with 57.1% of those who received fluconazole (Diflucan) followed by placebo (P < .001), according to Mycovia.

The most common side effects reported in phase 3 clinical studies were headache (7.4%) and nausea (3.6%), the company said. Patients with a hypersensitivity to oteseconazole should not take the drug, nor should those who are of reproductive potential, pregnant, or lactating.

Mycovia said it plans to launch the drug in the second quarter of 2022.

Full prescribing information is available online.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved oteseconazole capsules (Vivjoa), an azole antifungal agent, for the prevention of recurrent yeast infections in women who are not of reproductive potential.

Oteseconazole inhibits CYP51, an enzyme fungi require to preserve the integrity of their cell walls and to grow properly, according to Mycovia, the drug’s manufacturer. It is the first FDA-approved product for the treatment of recurrent vulvovaginal candidiasis (RVVC).

Recurrent vulvovaginal candidiasis, or chronic yeast infection, affects an estimated 138 million women worldwide annually. The condition is defined as three or more symptomatic acute episodes of yeast infection within a 12-month period. The primary symptoms of RVVC include vaginal itching, burning, irritation, and inflammation. Some patients may also experience abnormal vaginal discharge and pain during sex or urination.

“A medicine with Vivjoa’s sustained efficacy combined with the clinical safety profile has been long needed, as until now, physicians and their patients have had no FDA-approved medications for RVVC,” Stephen Brand, PhD, chief development officer of Mycovia, said in a statement. “We are excited to be the first to offer a medication designed specifically for RVVC, a challenging and chronic condition that is expected to increase in prevalence over the next decade.”

Approval for oteseconazole was based on results of three phase 3 trials involving 875 patients at 232 sites across 11 countries. In the U.S.-only ultraVIOLET trial, 89.7% of women with RVVC who received oteseconazole cleared their initial yeast infection and did not experience a recurrence during the 50-week maintenance period, compared with 57.1% of those who received fluconazole (Diflucan) followed by placebo (P < .001), according to Mycovia.

The most common side effects reported in phase 3 clinical studies were headache (7.4%) and nausea (3.6%), the company said. Patients with a hypersensitivity to oteseconazole should not take the drug, nor should those who are of reproductive potential, pregnant, or lactating.

Mycovia said it plans to launch the drug in the second quarter of 2022.

Full prescribing information is available online.

A version of this article first appeared on Medscape.com.

Earlier this year, hospitals in India were dealing not only with the coronavirus pandemic but also with a surge in a potentially lethal fungal infection in patients previously treated for COVID-19. Mucormycosis, also known as black fungus, is typically a rare infection, but India had recorded more than 45,000 cases as of July 2021.

Now, a recent report suggests that patients with COVID-19–associated rhino-orbital cerebral mucormycosis (CAM) may have a higher mortality rate than previously estimated. At highest risk, CAM patients with severe COVID-19 or orbital disease are more likely to die within 10 days of admission. The study was published Dec. 9 in JAMA Ophthalmology.

“The mortality indicators we observed, such as assisted ventilation and presence of severe orbital manifestations, can help physicians triage patients for emergency procedures, such as functional endoscopic sinus surgery (FESS), and administer systemic antifungal agents when in short supply,” the study authors wrote.

Mucormycosis usually infects immunocompromised patients. Previous research has found that poorly controlled diabetes – an epidemic in India – and use of high-dose systemic corticosteroids are two main risk factors for developing CAM. Even before COVID-19, India had a high incidence of mucormycosis compared to other countries, but cases exist around the world. In fact, on Dec. 17, the Centers for Disease Control and Prevention reported 10 isolated cases of COVID-19–associated mucormycosis identified in Arkansas hospitals between July and September 2021.

The disease can cause blurred vision, black lesions on the nose or inside of the mouth, and facial swelling. In rhino-orbital cerebral mucormycosis, extensive infection can necessitate orbital exenteration surgery, a disfiguring procedure that typically involves removal of the entire contents of the bony eye socket, as well as removal of the sinuses. Estimates for the mortality rate for this disease range from 14% to nearly 80%.

To better understand the cumulative morality rates for CAM and to identify additional risk factors, researchers reviewed the medical records of patients diagnosed and treated for CAM at a tertiary care multispecialty government hospital in Maharashtra, a state in the west-central region of India. The analysis included patients who died after admission or who had at minimum 30 days of documented follow-up. All diagnoses occurred between March 1 and May 30, 2021. All patients underwent comprehensive ophthalmic exams and routine blood workups.

Seventy-three patients were included in the study, with the average age of 53.5 years; 66% of the patients were male, and 74% of all patients had diabetes. Of the 47 individuals with available COVID-19 vaccination information, 89% had not had either shot of the vaccine, and 11% had the first dose. No patients in the cohort had received both doses of the vaccine; 87% of the patients were previously hospitalized for COVID-19, with 43 needing supplemental oxygen, 14 receiving noninvasive ventilation and ventilator support (NIV), and three requiring mechanical ventilation.

Patients developed CAM a median of 28 days after being discharged from the hospital for COVID-19 treatment; 26 patients died, 18 patients underwent FESS, and five underwent orbital exenteration. While 36% of patients died overall, the researchers found the cumulative probability of death from CAM rose from 26% at day 7 to 53% at day 21. They also found that the patients who died had more severe COVID-19, indicated by more days spent on supplemental oxygen (P = .003) and increased need for NIV or mechanical ventilation (P = .02) compared to patients who survived CAM. Those who died also had poorer visual acuity, with 35% of the group having no light perception during examination compared to 6% of surviving CAM patients (P = .02).

These findings are largely “confirmatory to what we previously knew, which is that [CAM] is a very bad disease with high morbidity and high mortality,” Ilan Schwartz, MD, PHD, an infectious disease physician at the University of Alberta, Edmonton, who researches emerging fungal infections, said in an interview. He was not involved with the research.

While larger studies looking at similar questions have been published, the new report has longer patient follow-up and is “better positioned to be able to estimate the mortality rate,” Dr. Schwartz noted. Even with 30 days of follow-up, “patients can have ongoing problems for many months, and so it’s possible that the true mortality rate is even higher, once you get beyond that period,” he added.

But Santosh G. Honavar, MD, the director of medical services at the Centre for Sight Eye Hospital in Hyderabad, India, also unaffiliated with the study, noted that the subset of patients included in the latest report may have had much more severe infection – and subsequently higher mortality rates – than a more generalized study in a broader patient population.

For example, a study by Mrittika Sen, PhD, Dr. Honavar, and their coauthors, published in the Indian Journal of Ophthalmology earlier this year, found a mortality rate of 14% when they examined the records of more than 2,800 patients across 102 treatment centers.

Taking that into account, “we believe that the actual mortality may be somewhere between the 14% reported by Sen et al. from the large Indian series and the 53% that we report at 3 weeks,” the JAMA Ophthalmology authors wrote.

Dr. Honavar also noted that the new report of severe infection outcomes identifies subgroups at higher risk of death due to CAM: those with severe COVID-19 infection or orbital disease. These groups “would need higher surveillance for mucormycosis, thus enabling early diagnosis and prompt initiation of amphotericin B upon diagnosis of mucormycosis,” he said in an interview. “These measures can possibly minimize the risk of death.”

Ongoing research on CAM cases will continue to inform knowledge and treatment of the disease, but there are still unanswered questions. “We still have a fairly unsatisfactory understanding of exactly why this [CAM] epidemic occurred and why it was so bad,” Dr. Schwartz noted. And while mucormycosis cases have seemed to drop off since the surge earlier this year, “I don’t think we’re out of the woods,” he added. “There’s a lot more awareness in India and around the world about this disease now, but we’re still quite vulnerable to seeing it again.”

Dr. Honavar is the editor-in-chief of the Indian Journal of Ophthalmology. Dr. Schwartz reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Earlier this year, hospitals in India were dealing not only with the coronavirus pandemic but also with a surge in a potentially lethal fungal infection in patients previously treated for COVID-19. Mucormycosis, also known as black fungus, is typically a rare infection, but India had recorded more than 45,000 cases as of July 2021.

Now, a recent report suggests that patients with COVID-19–associated rhino-orbital cerebral mucormycosis (CAM) may have a higher mortality rate than previously estimated. At highest risk, CAM patients with severe COVID-19 or orbital disease are more likely to die within 10 days of admission. The study was published Dec. 9 in JAMA Ophthalmology.

“The mortality indicators we observed, such as assisted ventilation and presence of severe orbital manifestations, can help physicians triage patients for emergency procedures, such as functional endoscopic sinus surgery (FESS), and administer systemic antifungal agents when in short supply,” the study authors wrote.

Mucormycosis usually infects immunocompromised patients. Previous research has found that poorly controlled diabetes – an epidemic in India – and use of high-dose systemic corticosteroids are two main risk factors for developing CAM. Even before COVID-19, India had a high incidence of mucormycosis compared to other countries, but cases exist around the world. In fact, on Dec. 17, the Centers for Disease Control and Prevention reported 10 isolated cases of COVID-19–associated mucormycosis identified in Arkansas hospitals between July and September 2021.

The disease can cause blurred vision, black lesions on the nose or inside of the mouth, and facial swelling. In rhino-orbital cerebral mucormycosis, extensive infection can necessitate orbital exenteration surgery, a disfiguring procedure that typically involves removal of the entire contents of the bony eye socket, as well as removal of the sinuses. Estimates for the mortality rate for this disease range from 14% to nearly 80%.

To better understand the cumulative morality rates for CAM and to identify additional risk factors, researchers reviewed the medical records of patients diagnosed and treated for CAM at a tertiary care multispecialty government hospital in Maharashtra, a state in the west-central region of India. The analysis included patients who died after admission or who had at minimum 30 days of documented follow-up. All diagnoses occurred between March 1 and May 30, 2021. All patients underwent comprehensive ophthalmic exams and routine blood workups.

Seventy-three patients were included in the study, with the average age of 53.5 years; 66% of the patients were male, and 74% of all patients had diabetes. Of the 47 individuals with available COVID-19 vaccination information, 89% had not had either shot of the vaccine, and 11% had the first dose. No patients in the cohort had received both doses of the vaccine; 87% of the patients were previously hospitalized for COVID-19, with 43 needing supplemental oxygen, 14 receiving noninvasive ventilation and ventilator support (NIV), and three requiring mechanical ventilation.

Patients developed CAM a median of 28 days after being discharged from the hospital for COVID-19 treatment; 26 patients died, 18 patients underwent FESS, and five underwent orbital exenteration. While 36% of patients died overall, the researchers found the cumulative probability of death from CAM rose from 26% at day 7 to 53% at day 21. They also found that the patients who died had more severe COVID-19, indicated by more days spent on supplemental oxygen (P = .003) and increased need for NIV or mechanical ventilation (P = .02) compared to patients who survived CAM. Those who died also had poorer visual acuity, with 35% of the group having no light perception during examination compared to 6% of surviving CAM patients (P = .02).

These findings are largely “confirmatory to what we previously knew, which is that [CAM] is a very bad disease with high morbidity and high mortality,” Ilan Schwartz, MD, PHD, an infectious disease physician at the University of Alberta, Edmonton, who researches emerging fungal infections, said in an interview. He was not involved with the research.

While larger studies looking at similar questions have been published, the new report has longer patient follow-up and is “better positioned to be able to estimate the mortality rate,” Dr. Schwartz noted. Even with 30 days of follow-up, “patients can have ongoing problems for many months, and so it’s possible that the true mortality rate is even higher, once you get beyond that period,” he added.

But Santosh G. Honavar, MD, the director of medical services at the Centre for Sight Eye Hospital in Hyderabad, India, also unaffiliated with the study, noted that the subset of patients included in the latest report may have had much more severe infection – and subsequently higher mortality rates – than a more generalized study in a broader patient population.

For example, a study by Mrittika Sen, PhD, Dr. Honavar, and their coauthors, published in the Indian Journal of Ophthalmology earlier this year, found a mortality rate of 14% when they examined the records of more than 2,800 patients across 102 treatment centers.

Taking that into account, “we believe that the actual mortality may be somewhere between the 14% reported by Sen et al. from the large Indian series and the 53% that we report at 3 weeks,” the JAMA Ophthalmology authors wrote.

Dr. Honavar also noted that the new report of severe infection outcomes identifies subgroups at higher risk of death due to CAM: those with severe COVID-19 infection or orbital disease. These groups “would need higher surveillance for mucormycosis, thus enabling early diagnosis and prompt initiation of amphotericin B upon diagnosis of mucormycosis,” he said in an interview. “These measures can possibly minimize the risk of death.”

Ongoing research on CAM cases will continue to inform knowledge and treatment of the disease, but there are still unanswered questions. “We still have a fairly unsatisfactory understanding of exactly why this [CAM] epidemic occurred and why it was so bad,” Dr. Schwartz noted. And while mucormycosis cases have seemed to drop off since the surge earlier this year, “I don’t think we’re out of the woods,” he added. “There’s a lot more awareness in India and around the world about this disease now, but we’re still quite vulnerable to seeing it again.”

Dr. Honavar is the editor-in-chief of the Indian Journal of Ophthalmology. Dr. Schwartz reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Earlier this year, hospitals in India were dealing not only with the coronavirus pandemic but also with a surge in a potentially lethal fungal infection in patients previously treated for COVID-19. Mucormycosis, also known as black fungus, is typically a rare infection, but India had recorded more than 45,000 cases as of July 2021.

Now, a recent report suggests that patients with COVID-19–associated rhino-orbital cerebral mucormycosis (CAM) may have a higher mortality rate than previously estimated. At highest risk, CAM patients with severe COVID-19 or orbital disease are more likely to die within 10 days of admission. The study was published Dec. 9 in JAMA Ophthalmology.

“The mortality indicators we observed, such as assisted ventilation and presence of severe orbital manifestations, can help physicians triage patients for emergency procedures, such as functional endoscopic sinus surgery (FESS), and administer systemic antifungal agents when in short supply,” the study authors wrote.

Mucormycosis usually infects immunocompromised patients. Previous research has found that poorly controlled diabetes – an epidemic in India – and use of high-dose systemic corticosteroids are two main risk factors for developing CAM. Even before COVID-19, India had a high incidence of mucormycosis compared to other countries, but cases exist around the world. In fact, on Dec. 17, the Centers for Disease Control and Prevention reported 10 isolated cases of COVID-19–associated mucormycosis identified in Arkansas hospitals between July and September 2021.

The disease can cause blurred vision, black lesions on the nose or inside of the mouth, and facial swelling. In rhino-orbital cerebral mucormycosis, extensive infection can necessitate orbital exenteration surgery, a disfiguring procedure that typically involves removal of the entire contents of the bony eye socket, as well as removal of the sinuses. Estimates for the mortality rate for this disease range from 14% to nearly 80%.

To better understand the cumulative morality rates for CAM and to identify additional risk factors, researchers reviewed the medical records of patients diagnosed and treated for CAM at a tertiary care multispecialty government hospital in Maharashtra, a state in the west-central region of India. The analysis included patients who died after admission or who had at minimum 30 days of documented follow-up. All diagnoses occurred between March 1 and May 30, 2021. All patients underwent comprehensive ophthalmic exams and routine blood workups.

Seventy-three patients were included in the study, with the average age of 53.5 years; 66% of the patients were male, and 74% of all patients had diabetes. Of the 47 individuals with available COVID-19 vaccination information, 89% had not had either shot of the vaccine, and 11% had the first dose. No patients in the cohort had received both doses of the vaccine; 87% of the patients were previously hospitalized for COVID-19, with 43 needing supplemental oxygen, 14 receiving noninvasive ventilation and ventilator support (NIV), and three requiring mechanical ventilation.

Patients developed CAM a median of 28 days after being discharged from the hospital for COVID-19 treatment; 26 patients died, 18 patients underwent FESS, and five underwent orbital exenteration. While 36% of patients died overall, the researchers found the cumulative probability of death from CAM rose from 26% at day 7 to 53% at day 21. They also found that the patients who died had more severe COVID-19, indicated by more days spent on supplemental oxygen (P = .003) and increased need for NIV or mechanical ventilation (P = .02) compared to patients who survived CAM. Those who died also had poorer visual acuity, with 35% of the group having no light perception during examination compared to 6% of surviving CAM patients (P = .02).

These findings are largely “confirmatory to what we previously knew, which is that [CAM] is a very bad disease with high morbidity and high mortality,” Ilan Schwartz, MD, PHD, an infectious disease physician at the University of Alberta, Edmonton, who researches emerging fungal infections, said in an interview. He was not involved with the research.

While larger studies looking at similar questions have been published, the new report has longer patient follow-up and is “better positioned to be able to estimate the mortality rate,” Dr. Schwartz noted. Even with 30 days of follow-up, “patients can have ongoing problems for many months, and so it’s possible that the true mortality rate is even higher, once you get beyond that period,” he added.

But Santosh G. Honavar, MD, the director of medical services at the Centre for Sight Eye Hospital in Hyderabad, India, also unaffiliated with the study, noted that the subset of patients included in the latest report may have had much more severe infection – and subsequently higher mortality rates – than a more generalized study in a broader patient population.

For example, a study by Mrittika Sen, PhD, Dr. Honavar, and their coauthors, published in the Indian Journal of Ophthalmology earlier this year, found a mortality rate of 14% when they examined the records of more than 2,800 patients across 102 treatment centers.

Taking that into account, “we believe that the actual mortality may be somewhere between the 14% reported by Sen et al. from the large Indian series and the 53% that we report at 3 weeks,” the JAMA Ophthalmology authors wrote.

Dr. Honavar also noted that the new report of severe infection outcomes identifies subgroups at higher risk of death due to CAM: those with severe COVID-19 infection or orbital disease. These groups “would need higher surveillance for mucormycosis, thus enabling early diagnosis and prompt initiation of amphotericin B upon diagnosis of mucormycosis,” he said in an interview. “These measures can possibly minimize the risk of death.”

Ongoing research on CAM cases will continue to inform knowledge and treatment of the disease, but there are still unanswered questions. “We still have a fairly unsatisfactory understanding of exactly why this [CAM] epidemic occurred and why it was so bad,” Dr. Schwartz noted. And while mucormycosis cases have seemed to drop off since the surge earlier this year, “I don’t think we’re out of the woods,” he added. “There’s a lot more awareness in India and around the world about this disease now, but we’re still quite vulnerable to seeing it again.”

Dr. Honavar is the editor-in-chief of the Indian Journal of Ophthalmology. Dr. Schwartz reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study from Orange County, California, shows how Candida auris, an emerging pathogen, was successfully identified and contained in long-term acute care hospitals (LTACHs) and ventilator-capable skilled-nursing facilities (vSNFs).

Lead author Ellora Karmarkar, MD, MSc, formerly an epidemic intelligence service officer with the Centers for Disease Control and Prevention and currently with the California Department of Public Health, said in an interview that the prospective surveillance of urine cultures for C. auris was prompted by “seeing what was happening in New York, New Jersey, and Illinois [being] pretty alarming for a lot of the health officials in California, [who] know that LTACHs are high-risk facilities because they take care of really sick people. Some of those people are there for a very long time.”

Therefore, the study authors decided to focus their investigations there, rather than in acute care hospitals, which were believed to be at lower risk for C. auris outbreaks.

The Orange County Health Department, working with the California Department of Health and the CDC, asked labs to prospectively identify all Candida isolates in urines from LTACHs between September 2018 and February 2019. Normally, labs do not speciate Candida from nonsterile body sites.

Dan Diekema, MD, an epidemiologist and clinical microbiologist at the University of Iowa, Iowa City, who was not involved in the study, told this news organization, “Acute care hospitals really ought to be moving toward doing species identification of Candida from nonsterile sites if they really want to have a better chance of detecting this early.”

The OCHD also screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%-10% of colonized patients later develop invasive infections, and 30%-60% die.

The first bloodstream infection was detected in May 2019. Per the report, published online Sept. 7 in Annals of Internal Medicine, “As of 1 January 2020, of 182 patients, 22 (12%) died within 30 days of C. auris identification; 47 (26%) died within 90 days. One of 47 deaths was attributed to C. auris.” Whole-genome sequencing showed that the isolates were all closely related in clade III.

Experts conducted extensive education in infection control at the LTACHs, and communication among the LTACHs and between the long-term facilities and acute care hospitals was improved. As a result, receiving facilities accepting transfers began culturing their newly admitted patients and quickly identified 4 of 99 patients with C. auris who had no known history of colonization. By October 2019, the outbreak was contained in two facilities, down from the nine where C. auris was initially found.

Dr. Diekema noted, “The challenge, of course, for a new emerging MDRO [multidrug-resistant organism] like Candida auris, is that the initial approach, in general, has to be almost passive, when you have not seen the organism. ... Passive surveillance means that you just carefully monitor your clinical cultures, and the first time you detect the MDRO of concern, then you begin doing the point prevalence surveys. ... This [prospective] kind of approach is really good for how we should move forward with both initial detection and containment of MDRO spread.”

Many outbreak studies are confined to a particular institution. Authors of an accompanying editorial commented that this study “underlines the importance of proactive protocols for outbreak investigations and containment measures across the entirety of the health care network serving at-risk patients.”

In her research, Dr. Karmarkar observed that, “some of these facilities don’t have the same infrastructure and infection prevention and control that an acute care hospital might.”

She said in an interview that, “one of the challenges was that people were so focused on COVID that they forgot about the MDROs. ... Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care. ... What I appreciated about this investigation is that every facility that we went to was so open to learning, so happy to have us there. They’re very interested in learning about Candida auris and understanding what they could do to control it.”

While recent attention has been on the frightening levels of multidrug resistance in C. auris, Dr. Karmarkar concluded that the “central message in our investigation is that with the right effort, the right approach, and the right team this is an intervenable issue. It’s not inevitable if the attention is focused on it to pick it up early and then try to contain it.”

Dr. Karmarkar reports no relevant financial relationships. Dr. Diekema reports research funding from bioMerieux and consulting fees from Opgen.

A version of this article first appeared on Medscape.com.

A new study from Orange County, California, shows how Candida auris, an emerging pathogen, was successfully identified and contained in long-term acute care hospitals (LTACHs) and ventilator-capable skilled-nursing facilities (vSNFs).

Lead author Ellora Karmarkar, MD, MSc, formerly an epidemic intelligence service officer with the Centers for Disease Control and Prevention and currently with the California Department of Public Health, said in an interview that the prospective surveillance of urine cultures for C. auris was prompted by “seeing what was happening in New York, New Jersey, and Illinois [being] pretty alarming for a lot of the health officials in California, [who] know that LTACHs are high-risk facilities because they take care of really sick people. Some of those people are there for a very long time.”

Therefore, the study authors decided to focus their investigations there, rather than in acute care hospitals, which were believed to be at lower risk for C. auris outbreaks.

The Orange County Health Department, working with the California Department of Health and the CDC, asked labs to prospectively identify all Candida isolates in urines from LTACHs between September 2018 and February 2019. Normally, labs do not speciate Candida from nonsterile body sites.

Dan Diekema, MD, an epidemiologist and clinical microbiologist at the University of Iowa, Iowa City, who was not involved in the study, told this news organization, “Acute care hospitals really ought to be moving toward doing species identification of Candida from nonsterile sites if they really want to have a better chance of detecting this early.”

The OCHD also screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%-10% of colonized patients later develop invasive infections, and 30%-60% die.

The first bloodstream infection was detected in May 2019. Per the report, published online Sept. 7 in Annals of Internal Medicine, “As of 1 January 2020, of 182 patients, 22 (12%) died within 30 days of C. auris identification; 47 (26%) died within 90 days. One of 47 deaths was attributed to C. auris.” Whole-genome sequencing showed that the isolates were all closely related in clade III.

Experts conducted extensive education in infection control at the LTACHs, and communication among the LTACHs and between the long-term facilities and acute care hospitals was improved. As a result, receiving facilities accepting transfers began culturing their newly admitted patients and quickly identified 4 of 99 patients with C. auris who had no known history of colonization. By October 2019, the outbreak was contained in two facilities, down from the nine where C. auris was initially found.

Dr. Diekema noted, “The challenge, of course, for a new emerging MDRO [multidrug-resistant organism] like Candida auris, is that the initial approach, in general, has to be almost passive, when you have not seen the organism. ... Passive surveillance means that you just carefully monitor your clinical cultures, and the first time you detect the MDRO of concern, then you begin doing the point prevalence surveys. ... This [prospective] kind of approach is really good for how we should move forward with both initial detection and containment of MDRO spread.”

Many outbreak studies are confined to a particular institution. Authors of an accompanying editorial commented that this study “underlines the importance of proactive protocols for outbreak investigations and containment measures across the entirety of the health care network serving at-risk patients.”

In her research, Dr. Karmarkar observed that, “some of these facilities don’t have the same infrastructure and infection prevention and control that an acute care hospital might.”

She said in an interview that, “one of the challenges was that people were so focused on COVID that they forgot about the MDROs. ... Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care. ... What I appreciated about this investigation is that every facility that we went to was so open to learning, so happy to have us there. They’re very interested in learning about Candida auris and understanding what they could do to control it.”

While recent attention has been on the frightening levels of multidrug resistance in C. auris, Dr. Karmarkar concluded that the “central message in our investigation is that with the right effort, the right approach, and the right team this is an intervenable issue. It’s not inevitable if the attention is focused on it to pick it up early and then try to contain it.”

Dr. Karmarkar reports no relevant financial relationships. Dr. Diekema reports research funding from bioMerieux and consulting fees from Opgen.

A version of this article first appeared on Medscape.com.

A new study from Orange County, California, shows how Candida auris, an emerging pathogen, was successfully identified and contained in long-term acute care hospitals (LTACHs) and ventilator-capable skilled-nursing facilities (vSNFs).

Lead author Ellora Karmarkar, MD, MSc, formerly an epidemic intelligence service officer with the Centers for Disease Control and Prevention and currently with the California Department of Public Health, said in an interview that the prospective surveillance of urine cultures for C. auris was prompted by “seeing what was happening in New York, New Jersey, and Illinois [being] pretty alarming for a lot of the health officials in California, [who] know that LTACHs are high-risk facilities because they take care of really sick people. Some of those people are there for a very long time.”

Therefore, the study authors decided to focus their investigations there, rather than in acute care hospitals, which were believed to be at lower risk for C. auris outbreaks.

The Orange County Health Department, working with the California Department of Health and the CDC, asked labs to prospectively identify all Candida isolates in urines from LTACHs between September 2018 and February 2019. Normally, labs do not speciate Candida from nonsterile body sites.

Dan Diekema, MD, an epidemiologist and clinical microbiologist at the University of Iowa, Iowa City, who was not involved in the study, told this news organization, “Acute care hospitals really ought to be moving toward doing species identification of Candida from nonsterile sites if they really want to have a better chance of detecting this early.”

The OCHD also screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%-10% of colonized patients later develop invasive infections, and 30%-60% die.

The first bloodstream infection was detected in May 2019. Per the report, published online Sept. 7 in Annals of Internal Medicine, “As of 1 January 2020, of 182 patients, 22 (12%) died within 30 days of C. auris identification; 47 (26%) died within 90 days. One of 47 deaths was attributed to C. auris.” Whole-genome sequencing showed that the isolates were all closely related in clade III.

Experts conducted extensive education in infection control at the LTACHs, and communication among the LTACHs and between the long-term facilities and acute care hospitals was improved. As a result, receiving facilities accepting transfers began culturing their newly admitted patients and quickly identified 4 of 99 patients with C. auris who had no known history of colonization. By October 2019, the outbreak was contained in two facilities, down from the nine where C. auris was initially found.

Dr. Diekema noted, “The challenge, of course, for a new emerging MDRO [multidrug-resistant organism] like Candida auris, is that the initial approach, in general, has to be almost passive, when you have not seen the organism. ... Passive surveillance means that you just carefully monitor your clinical cultures, and the first time you detect the MDRO of concern, then you begin doing the point prevalence surveys. ... This [prospective] kind of approach is really good for how we should move forward with both initial detection and containment of MDRO spread.”

Many outbreak studies are confined to a particular institution. Authors of an accompanying editorial commented that this study “underlines the importance of proactive protocols for outbreak investigations and containment measures across the entirety of the health care network serving at-risk patients.”

In her research, Dr. Karmarkar observed that, “some of these facilities don’t have the same infrastructure and infection prevention and control that an acute care hospital might.”

She said in an interview that, “one of the challenges was that people were so focused on COVID that they forgot about the MDROs. ... Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care. ... What I appreciated about this investigation is that every facility that we went to was so open to learning, so happy to have us there. They’re very interested in learning about Candida auris and understanding what they could do to control it.”

While recent attention has been on the frightening levels of multidrug resistance in C. auris, Dr. Karmarkar concluded that the “central message in our investigation is that with the right effort, the right approach, and the right team this is an intervenable issue. It’s not inevitable if the attention is focused on it to pick it up early and then try to contain it.”

Dr. Karmarkar reports no relevant financial relationships. Dr. Diekema reports research funding from bioMerieux and consulting fees from Opgen.

A version of this article first appeared on Medscape.com.