Appropriate therapy reduces mortality in bloodstream infections due to carbapenemase-producing Enterobacteriaceae

Appropriate therapy was protective against mortality among patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae, whereas combination therapy was linked with improved survival only among patients who had a high mortality rate, according to findings recently published in Lancet Infectious Diseases.

“Among antibiotic-resistant organisms, carbapenemase-producing Enterobacteriaceae are probably the most worrying threat because the therapeutic options against these bacteria are very few,” Belen Gutierrez-Gutierrez, PhD, of Instituto de Biomedicina de Sevilla, Spain, and colleagues wrote. “The best available protection against CPE infection is unknown. Results from several retrospective studies suggest that combination therapy is better than monotherapy. Investigators of other studies did not find combination therapy to be better than monotherapy.”

The researchers performed a retrospective cohort study of 437 patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae between Jan. 1, 2004, and Dec. 31, 2013. All patients were recruited from 26 tertiary hospitals in 10 different countries. Gutierrez-Gutierrez and colleagues compared 30-day all-cause mortality between different groups of patients: those receiving appropriate therapy (including an active drug against the blood isolate within the first 5 days of infection) and those receiving inappropriate therapy, as well as between patients undergoing monotherapy or combination therapy.

Overall, 78% of patients (n = 343) received appropriate therapy, whereas 22% (n = 94) received inappropriate therapy, the researchers reported. The most common organism was Klebsiella pneumoniae, which was found in 86% of patients (85% of those receiving appropriate therapy vs. 89% of those receiving inappropriate therapy). The most common carbapenemase was K. pneumoniae carbapenemase, which occurred in 75% (n = 329) of patients overall. Appropriate therapy was associated with a lower mortality rate than inappropriate therapy (38.5% vs. 60.6%; adjusted HR = 0.45; 95% CI, 0.33-0.62), the researchers wrote.

Gutierrez-Gutierrez and colleagues reported that among patients who received appropriate therapy, 39% (n = 135) underwent combination therapy and 61% (n = 208) received monotherapy. Overall, there was no significant difference in the mortality rates between the two groups (35% vs. 41%; adjusted HR = 1.63; 95% CI, 0.67-3.91). When researchers stratified patients by mortality risk, however, combination therapy showed a lower mortality rate in the high-mortality-score stratum (48% vs 62%; adjusted HR = 0.56; 95% CI, 0.34-0.91). This did not hold true for the low-mortality-score stratum (24% vs. 20%; adjusted OR = 1.21; 95% CI, 0.56-2.56).

In an accompanying editorial, Mathias W. Pletz, MD, PhD, of the Center for Infectious Diseases and Infection Control at Jena University Hospital, Germany, and colleagues that “the broader [antibiotic] the better would be the wrong conclusion, not only from the perspective of antibiotic stewardship, but also from that of the individual patient.

“In the area of spreading antimicrobial resistance, we should use antibiotics only as much as needed and as little as possible — this conclusion also means an individualized approach is needed that identifies patients in need of combination therapy,” Pletz and colleagues wrote. “With rapid development of novel diagnostic tools for pathogen and resistance identification or measurement of antibiotic blood concentrations, the future challenge for infectious disease physicians will be to implement all of these data in a meaningful way to identify the best tailored antibiotic treatment for the individual patient.” – by Andy Polhamus

Disclosure: Pletz and colleagues report a grant from the German Federal Ministry of Education and Research. Gutierrez-Gutierrez reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.