Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem

J Antimicrob Chemother. 2019 Jan 1;74(1):177-181. doi: 10.1093/jac/dky406.

Abstract

Background: In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria.

Methods: We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to β-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS.

Results: Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued.

Conclusions: Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Drug Synergism*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Fosfomycin / administration & dosage
  • Fosfomycin / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Male
  • Meropenem / administration & dosage
  • Meropenem / pharmacology*
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Middle Aged
  • Pneumonia, Ventilator-Associated / drug therapy
  • Pneumonia, Ventilator-Associated / microbiology
  • Sepsis / drug therapy
  • Sepsis / microbiology
  • Surgical Wound Infection / drug therapy
  • Surgical Wound Infection / microbiology
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Fosfomycin
  • Meropenem