Combination therapy with polymyxin B for carbapenemase-producing Klebsiella pneumoniae bloodstream infection

Int J Antimicrob Agents. 2019 Feb;53(2):152-157. doi: 10.1016/j.ijantimicag.2018.10.010. Epub 2018 Oct 26.

Abstract

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) bloodstream infections (BSIs) are related to high mortality rates, and combination therapy has been associated with lower mortality in patients treated mostly with colistin. There is a paucity of studies addressing polymyxin B (PMB) treatment for KPC-KP infections. This was a retrospective cohort study of patients with monomicrobial KPC-KP BSIs. The primary outcome was 30-day mortality. Antimicrobial therapy was defined as empirical (started within the first 48 h) or definitive (initiated after >48 h) and was evaluated as follows: monotherapy (only one in vitro active agent or combination therapy of one in vitro active agent plus one or more in vitro non-active agents); and combination therapy with two or more in vitro active agents. A total of 82 KPC-KP BSIs were included; 40 patients (48.8%) died in the first 30 days. Mortality of patients treated with the combination of two in vitro active antimicrobial agents, mostly PMB plus amikacin, was significantly lower (37.5%) compared with monotherapy (64.7%) (P= 0.01). Combination therapy [adjusted hazard ratio (aHR) = 0.40, 95% confidence interval (CI) 0.22-0.83; P = 0.01] was independently associated with lower 30-day survival when controlled for non-surgical admission (aHR = 2.33, 95% CI 1.14-4.80; P = 0.02) and use of vasoactive drugs (aHR = 7.37, 95% CI 3.01-18.02; P < 0.01). In conclusion, combination therapy with two in vitro active agents, mostly PMB plus amikacin, showed a survival benefit compared with other regimens.

Keywords: Amikacin; Carbapenem; Klebsiella pneumoniae; Mortality; Polymyxin B; β-Lactamase.

MeSH terms

  • Amikacin / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacterial Proteins / genetics
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Drug Therapy, Combination
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / mortality
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • Polymyxin B / therapeutic use*
  • Retrospective Studies
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Amikacin
  • beta-Lactamases
  • carbapenemase
  • Polymyxin B