Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia

Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01511-18. doi: 10.1128/AAC.01511-18. Print 2019 Jan.

Abstract

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-β-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.

Keywords: bacteremia; carbapenem-resistant Enterobacteriaceae; combination therapy; in-hospital mortality; monotherapy.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia / drug therapy
  • Bacteremia / mortality*
  • Bacterial Proteins / metabolism*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • China
  • Drug Therapy, Combination
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / mortality*
  • Female
  • Hospital Mortality
  • Humans
  • Inappropriate Prescribing / mortality
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Meropenem / therapeutic use
  • Microbial Sensitivity Tests
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index
  • Tigecycline / therapeutic use
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Tigecycline
  • beta-Lactamases
  • beta-lactamase KPC-2, Klebsiella pneumoniae
  • carbapenemase
  • Meropenem