Mechanisms of fosfomycin resistance in carbapenem-resistant Enterobacter sp

Bryan P White1, Kayla R Stover2, Katie E Barber3

  • 1Department of Pharmacy Services, University of Mississippi Medical Center, Jackson, MS, USA.

Insights

Most clinical blaKPC-positive Enterobacter strains remain susceptible to fosfomycin. However, the presence of the fosA gene, an enzyme conferring resistance, did not correlate with this susceptibility in the study.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Clinical Infectious Diseases

Background:

  • Carbapenemase-producing Enterobacteriaceae (CPE) are a significant global health threat.
  • Enterobacter species are common causes of hospital-acquired infections.
  • Fosfomycin is a valuable antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria.

Purpose of the Study:

  • To investigate fosfomycin susceptibility among clinical isolates of blaKPC-positive Enterobacter species.
  • To identify the prevalence of specific fosfomycin resistance genes (fosA, FosA3, FosC2) in these strains.
  • To determine the correlation between fosA gene presence and fosfomycin susceptibility.

Main Methods:

  • Phenotypic susceptibility testing to fosfomycin was performed on 19 clinical isolates of blaKPC-positive Enterobacter species.
  • Molecular methods (PCR) were used to detect the presence of fosfomycin resistance genes: fosA, FosA3, and FosC2.
  • Statistical analysis was conducted to assess the correlation between genotype (fosA presence) and phenotype (fosfomycin susceptibility).

Main Results:

  • Out of 19 blaKPC-positive Enterobacter strains, 14 (74%) exhibited susceptibility to fosfomycin.
  • The fosA gene was detected in 8 strains (42%), while FosA3 and FosC2 genes were not found in any of the tested isolates.
  • No significant correlation was observed between the presence of the fosA gene and fosfomycin susceptibility.

Conclusions:

  • A high proportion of clinical blaKPC-positive Enterobacter strains remain susceptible to fosfomycin, suggesting its potential utility in treating infections caused by these pathogens.
  • The fosA gene, a common mechanism of fosfomycin resistance, was prevalent but did not reliably predict susceptibility in this cohort.
  • Further research is warranted to elucidate other resistance mechanisms and optimize the use of fosfomycin against KPC-producing Enterobacter species.

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