In Vitro Activity and Clinical Efficacy of Faropenem against Third-Generation Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae

Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0012522. doi: 10.1128/aac.00125-22. Epub 2022 Jun 1.

Abstract

Faropenem (FRPM) is active against extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, but evidence for its efficacy is lacking. This study determined the correlation between the susceptibility by disk diffusion method and the MIC of FRPM for third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, and the effectiveness of FRPM for the treatment of urinary tract infection (UTI) caused by these two bacteria in a retrospective cohort analysis. Of the 48 third-generation cephalosporin-resistant clinical isolates tested, 44 isolates produced ESBL, and 8 isolates produced AmpC, including 4 isolates produced both ESBL and AmpC. Thirty-seven isolates had an FRPM MIC of ≤1 mg/L, and seven had an FRPM MIC of 2 mg/L. An FRPM MIC of >2 mg/L was observed with four isolates. In a retrospective cohort analysis, 63 patients with UTI treated with FRPM were identified. All isolates of ESBL-producing E. coli (n = 54) and K. pneumoniae (n = 9) treated with FRPM showed disk diffusion zone diameters larger than 16.0 mm (estimated MIC, 2.2 mg/L). All patients completed the scheduled treatment courses with FRPM, but 28- and 90-day relapses happened in 10 patients (16%) and 16 patients (25%), respectively. No significant risk factors for the 28- and 90-day relapses were found. FRPM can be used according to disk diffusion susceptibility testing in UTI. Further investigations are necessary to assess the clinical breakpoint of FRPM for ESBL-producing Enterobacterales and the candidates most likely to benefit from using FRPM.

Keywords: AmpC β-lactamase; Escherichia coli; Klebsiella pneumoniae; extended-spectrum β-lactamase; faropenem; urinary tract infection.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Escherichia coli
  • Escherichia coli Infections* / drug therapy
  • Escherichia coli Infections* / microbiology
  • Humans
  • Klebsiella pneumoniae
  • Microbial Sensitivity Tests
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Tract Infections* / drug therapy
  • Urinary Tract Infections* / microbiology
  • beta-Lactamases / therapeutic use
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • beta-Lactams
  • beta-Lactamases
  • fropenem