Assessing antimicrobial stewardship initiatives: Clinical evaluation of cefepime or piperacillin/tazobactam in patients with bloodstream infections secondary to AmpC-producing organisms

Int J Antimicrob Agents. 2018 Nov;52(5):719-723. doi: 10.1016/j.ijantimicag.2018.08.007. Epub 2018 Aug 17.

Abstract

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

Keywords: AmpC; Carbapenem-sparing; Cefepime; Piperacillin/tazobactam.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Antimicrobial Stewardship*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacterial Proteins / metabolism*
  • Cefepime / pharmacology
  • Cefepime / therapeutic use*
  • Drug Resistance, Bacterial
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / drug therapy*
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Piperacillin, Tazobactam Drug Combination / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Young Adult
  • beta-Lactamase Inhibitors / therapeutic use*
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • Cefepime
  • AmpC beta-lactamases
  • beta-Lactamases