title: Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.
abstract: Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream 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-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate 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% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs 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.
authors.affiliation: Columbia University Medical Center, New York, New York, USA ag2845@cumc.columbia.edu eyf2002@cumc.columbia.edu.
authors.forename: A
authors.initials: A
authors.lastname: Gomez-Simmonds
authors.affiliation: New York-Presbyterian Hospital, New York, New York, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nelson
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Eiras
authors.affiliation: New York-Presbyterian Hospital, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Loo
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Jenkins
authors.affiliation: Columbia University Medical Center, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Whittier
authors.affiliation: New York-Presbyterian Hospital, New York, New York, USA Weill Cornell Medical College, New York, New York, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Calfee
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Satlin
authors.affiliation: Columbia University Medical Center, New York, New York, USA New York-Presbyterian Hospital, New York, New York, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Kubin
authors.affiliation: Columbia University Medical Center, New York, New York, USA New York-Presbyterian Hospital, New York, New York, USA ag2845@cumc.columbia.edu eyf2002@cumc.columbia.edu.
authors.forename: E Y
authors.initials: EY
authors.lastname: Furuya
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D002511:Cephalosporins / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D013845:Thienamycins / Q000627:therapeutic use*; D016896:Treatment Outcome; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D007166:Immunosuppressive Agents; D013845:Thienamycins; D015378:Imipenem; D000077731:Meropenem