Combination regimens for the treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infections.
Antimicrob Agents Chemother. 2016 Apr 4;
Authors: Gomez-Simmonds A, Nelson B, Eiras DP, Loo A, Jenkins SG, Whittier S, Calfee DP, Satlin MJ, Kubin CJ, Furuya EY
Previous studies reported decreased mortality in patients with carbapenemase-producingKlebsiella pneumoniaebloodstream infections (BSIs) treated with combination therapy, but included carbapenem-susceptible and intermediate isolates as per revised CLSI breakpoints. Here we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistantK. pneumoniae(CRKP) according to the number ofin vitroactive agents received and whether an extended-spectrum beta-lactam antibiotic (BL), including meropenem or an extended-spectrum cephalosporin, was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006-2013, where all isolates had meropenem or imipenem MICs ≥4 μg/mL. Univariable and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% with SAA plus BL, 28% with multiple active agents (MAA), and 23% with MAA plus BL. 90% of isolates had meropenem MICs ≥16 μg/mL. 30-day mortality was 33% overall and did not significantly differ across the 4 treatment groups in a multivariable model (p=0.4); mortality was significantly associated with Pitt bacteremia score ≥4 (OR 7.7, 95% CI 3.2-18.1, p=0.1) and immunosuppression was protective (OR 0.4, 95% CI 0.2-1.0, p=0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAA versus MAA (26% versus 38%, p=0.1), or BL versus no BL (26% versus 39%, p=0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.
PMID: 27044555 [PubMed - as supplied by publisher]