Combination Therapy Gives Survival Edge in KPC Bacteremia

BOSTON – Bacteremia secondary to pneumonia caused by carbepenem-resistant Klebsiella pneumoniae carries a high mortality rate, but combination antimicrobial regimens involving polymyxins, tigecycline, or carbepenems offer a better shot at survival compared with monotherapy, according to the findings of an observational treatment study conducted at two medical centers.

Among 41 patients infected with K. pneumoniae bacteria that produce the drug-resistant Klebsiella pneumoniae Carbepenemase (KPC), 14-day mortality was 24%, and 28-day mortality was 35%, Dr. Zubair A. Qureshi reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Mortality was increased when patients received monotherapy with either colistin (4 deaths among 7 patients) or tigecycline (3 of 5 patients). However, there were no deaths within 28 days among patients treated with either colistin or tigecycline added to any carbepenem, even when the infectious organism was reported to be nonsusceptible to carbepenems, said Dr. Qureshi of the division of internal medicine at the University of Pittsburgh Medical Center.

He noted that the preliminary findings are supported by a recent review of KPC infections that documented better clinical outcomes with combination therapy compared with monotherapy (J. Antimicrob. Chemother. 2010;6:1119-25).

KPC type beta-lactamases have been shown to confer either decreased susceptibility or resistance to virtually all beta-lactam antibiotics, including the carbapenem class agents imipenem, meropenem, and ertapenem.

Investigators at the University of Pittsburgh and St. Luke’s-Roosevelt Hospital Center in New York City conducted the single-arm observational study of treatment outcomes in patients with bacteremia due to KPC-producing K. pneumoniae. Patients were screened for the presence of KPC by reduced susceptibility to ertapenem, which was confirmed with polymerase chain reaction.

The authors looked at risk factors, antimicrobial therapy, and in-hospital mortality rates. They identified 41 patients (24 women, 17 men) with KPC-producing K. pneumoniae, with a median age of 62 years (range 25-90 years). All of the cases appeared to have been acquired in either the hospital (78%) or other health care settings such as long-term care facilities. There were no identified cases of community-acquired infections.

The source of the bacteremia was vascular catheters in 29% of the cases, pneumonia in 27%, urinary tract in 15%, intra-abdominal in 4%, and superficial wounds in 4%. The source was unknown in the remaining patients.

The primary risk factor was immunocompromised status, either from a transplant, malignancy, diabetes, connective tissue disease, chronic renal failure, or HIV infection. In all, 76% of patients had recently received antimicrobial agents, and 41% were nursing-home residents.

Deaths occurred in 7 of 11 patients with pneumonia as the source of bacteremia, 3 of 12 patients with vascular catheters as the source, 1 of 6 with urinary catheter-based infections, and 3 of 12 from other or unknown sources.

When they looked at 28-day mortality in patients who received definitive therapy, they found that any combination was associated with a significantly lower rate than monotherapy (6% vs. 59%, P = .002). The analysis did not include two patients who were lost to follow-up.

The regimens consisted of various combinations of polymyxins, tigecycline, and carbapenems.

“The combination of colistin and carbepenem appears to be superior to any other antibiotic combination, but there is a need for more observation as well as randomized clinical trials to help define the optimal treatment for KPC infections,” Dr. Qureshi said.

Disclosures: Dr. Qureshi reported having no conflicts of interest. Several of his colleagues reported receiving consulting fees from AstraZeneca, Merck, Novartis, Leo Pharmaceuticals, Three Rivers Pharmaceuticals, and/or Johnson & Johnson.

BOSTON – Bacteremia secondary to pneumonia caused by carbepenem-resistant Klebsiella pneumoniae carries a high mortality rate, but combination antimicrobial regimens involving polymyxins, tigecycline, or carbepenems offer a better shot at survival compared with monotherapy, according to the findings of an observational treatment study conducted at two medical centers.

Among 41 patients infected with K. pneumoniae bacteria that produce the drug-resistant Klebsiella pneumoniae Carbepenemase (KPC), 14-day mortality was 24%, and 28-day mortality was 35%, Dr. Zubair A. Qureshi reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Mortality was increased when patients received monotherapy with either colistin (4 deaths among 7 patients) or tigecycline (3 of 5 patients). However, there were no deaths within 28 days among patients treated with either colistin or tigecycline added to any carbepenem, even when the infectious organism was reported to be nonsusceptible to carbepenems, said Dr. Qureshi of the division of internal medicine at the University of Pittsburgh Medical Center.

He noted that the preliminary findings are supported by a recent review of KPC infections that documented better clinical outcomes with combination therapy compared with monotherapy (J. Antimicrob. Chemother. 2010;6:1119-25).

KPC type beta-lactamases have been shown to confer either decreased susceptibility or resistance to virtually all beta-lactam antibiotics, including the carbapenem class agents imipenem, meropenem, and ertapenem.

Investigators at the University of Pittsburgh and St. Luke’s-Roosevelt Hospital Center in New York City conducted the single-arm observational study of treatment outcomes in patients with bacteremia due to KPC-producing K. pneumoniae. Patients were screened for the presence of KPC by reduced susceptibility to ertapenem, which was confirmed with polymerase chain reaction.

The authors looked at risk factors, antimicrobial therapy, and in-hospital mortality rates. They identified 41 patients (24 women, 17 men) with KPC-producing K. pneumoniae, with a median age of 62 years (range 25-90 years). All of the cases appeared to have been acquired in either the hospital (78%) or other health care settings such as long-term care facilities. There were no identified cases of community-acquired infections.

The source of the bacteremia was vascular catheters in 29% of the cases, pneumonia in 27%, urinary tract in 15%, intra-abdominal in 4%, and superficial wounds in 4%. The source was unknown in the remaining patients.

The primary risk factor was immunocompromised status, either from a transplant, malignancy, diabetes, connective tissue disease, chronic renal failure, or HIV infection. In all, 76% of patients had recently received antimicrobial agents, and 41% were nursing-home residents.

Deaths occurred in 7 of 11 patients with pneumonia as the source of bacteremia, 3 of 12 patients with vascular catheters as the source, 1 of 6 with urinary catheter-based infections, and 3 of 12 from other or unknown sources.

When they looked at 28-day mortality in patients who received definitive therapy, they found that any combination was associated with a significantly lower rate than monotherapy (6% vs. 59%, P = .002). The analysis did not include two patients who were lost to follow-up.

The regimens consisted of various combinations of polymyxins, tigecycline, and carbapenems.

“The combination of colistin and carbepenem appears to be superior to any other antibiotic combination, but there is a need for more observation as well as randomized clinical trials to help define the optimal treatment for KPC infections,” Dr. Qureshi said.

Disclosures: Dr. Qureshi reported having no conflicts of interest. Several of his colleagues reported receiving consulting fees from AstraZeneca, Merck, Novartis, Leo Pharmaceuticals, Three Rivers Pharmaceuticals, and/or Johnson & Johnson.

BOSTON – Bacteremia secondary to pneumonia caused by carbepenem-resistant Klebsiella pneumoniae carries a high mortality rate, but combination antimicrobial regimens involving polymyxins, tigecycline, or carbepenems offer a better shot at survival compared with monotherapy, according to the findings of an observational treatment study conducted at two medical centers.

Among 41 patients infected with K. pneumoniae bacteria that produce the drug-resistant Klebsiella pneumoniae Carbepenemase (KPC), 14-day mortality was 24%, and 28-day mortality was 35%, Dr. Zubair A. Qureshi reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Mortality was increased when patients received monotherapy with either colistin (4 deaths among 7 patients) or tigecycline (3 of 5 patients). However, there were no deaths within 28 days among patients treated with either colistin or tigecycline added to any carbepenem, even when the infectious organism was reported to be nonsusceptible to carbepenems, said Dr. Qureshi of the division of internal medicine at the University of Pittsburgh Medical Center.

He noted that the preliminary findings are supported by a recent review of KPC infections that documented better clinical outcomes with combination therapy compared with monotherapy (J. Antimicrob. Chemother. 2010;6:1119-25).

KPC type beta-lactamases have been shown to confer either decreased susceptibility or resistance to virtually all beta-lactam antibiotics, including the carbapenem class agents imipenem, meropenem, and ertapenem.

Investigators at the University of Pittsburgh and St. Luke’s-Roosevelt Hospital Center in New York City conducted the single-arm observational study of treatment outcomes in patients with bacteremia due to KPC-producing K. pneumoniae. Patients were screened for the presence of KPC by reduced susceptibility to ertapenem, which was confirmed with polymerase chain reaction.

The authors looked at risk factors, antimicrobial therapy, and in-hospital mortality rates. They identified 41 patients (24 women, 17 men) with KPC-producing K. pneumoniae, with a median age of 62 years (range 25-90 years). All of the cases appeared to have been acquired in either the hospital (78%) or other health care settings such as long-term care facilities. There were no identified cases of community-acquired infections.

The source of the bacteremia was vascular catheters in 29% of the cases, pneumonia in 27%, urinary tract in 15%, intra-abdominal in 4%, and superficial wounds in 4%. The source was unknown in the remaining patients.

The primary risk factor was immunocompromised status, either from a transplant, malignancy, diabetes, connective tissue disease, chronic renal failure, or HIV infection. In all, 76% of patients had recently received antimicrobial agents, and 41% were nursing-home residents.

Deaths occurred in 7 of 11 patients with pneumonia as the source of bacteremia, 3 of 12 patients with vascular catheters as the source, 1 of 6 with urinary catheter-based infections, and 3 of 12 from other or unknown sources.

When they looked at 28-day mortality in patients who received definitive therapy, they found that any combination was associated with a significantly lower rate than monotherapy (6% vs. 59%, P = .002). The analysis did not include two patients who were lost to follow-up.

The regimens consisted of various combinations of polymyxins, tigecycline, and carbapenems.

“The combination of colistin and carbepenem appears to be superior to any other antibiotic combination, but there is a need for more observation as well as randomized clinical trials to help define the optimal treatment for KPC infections,” Dr. Qureshi said.

Disclosures: Dr. Qureshi reported having no conflicts of interest. Several of his colleagues reported receiving consulting fees from AstraZeneca, Merck, Novartis, Leo Pharmaceuticals, Three Rivers Pharmaceuticals, and/or Johnson & Johnson.