Evaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill Curves

Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02549-18. doi: 10.1128/AAC.02549-18. Print 2019 May.

Abstract

The effects of combining fosfomycin with various antimicrobial agents were evaluated in vitro by broth microdilution checkerboard and time-kill kinetic studies. Checkerboard analyses were used to evaluate the following 30 Gram-negative isolates: 5 Pseudomonas aeruginosa, 5 Acinetobacter baumannii-Acinetobacter calcoaceticus species complex, and 20 Enterobacteriaceae isolates. No isolate exhibited antagonism when fosfomycin was tested in combination, and synergy was observed in more than 25% of the drug combinations tested. The most frequent instances of synergy occurred when testing fosfomycin with β-lactams. Two isolates of Pseudomonas aeruginosa, 2 of Klebsiella pneumoniae, and 1 of the A. baumannii-A. calcoaceticus species complex that exhibited synergy when fosfomycin was tested in combination were subjected to time-kill kinetic analyses for confirmation. Time-kill assays confirmed synergistic activity. These data indicated that combination therapy with fosfomycin may be beneficial.

Keywords: fosfomycin; synergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Fosfomycin / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Kinetics
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Fosfomycin