Combo Therapy Gives Survival Edge in KPC Bacteremia
Any combination was linked with significantly lower mortality, compared with monotherapy.
BY NEIL OSTERWEIL
Elsevier Global Medical News
BOSTON – Bacteremia secondary to pneumonia caused by carbapenem-resistant Klebsiella pneumoniae carries a high mortality rate, but combination antimicrobial regimens involving polymyxins, tigecycline, or carbapenems improve 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 Klebsiella pneumoniae carbapenemase (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 deaths among 5 patients). However, there were no deaths within 28 days among patients treated with either colistin or tigecycline added to any carbapenem, even when the infectious organism was reported to be nonsusceptible to carbapenems, said Dr. Qureshi of the division of internal medicine at the University of Pittsburgh Medical Center.
He noted that the preliminary findings are consistent with 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 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.
Death 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 patients with urinary catheter-based infections, and 3 of 12 patients whose infections were due to other or unknown sources.
When the investigators looked at 28-day mortality in patients who received definitive therapy, they found that any combination was associated with significantly lower mortality, compared with 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 carbapenem 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.
Vitals
Major Finding: Combining a carbapenem antibiotic with either colistin or tigecycline improved 28-day survival in patients with bacteremia secondary to pneumonia caused by KPC, compared with those who received monotherapy (6% vs. 59%, P= .002).
Data Source: Single-arm observational study.
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.
