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Exposure of Staphylococcus aureus to subinhibitory concentrations of β-lactam antibiotics induces heterogeneous

Mélanie Roch1, Perrine Clair2, Adriana Renzoni3

  • 1International Center for Infectiology Research, Université de Lyon, Lyon, France INSERM U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Lyon, France CNRS, UMR5308, Lyon, France Hospices Civils de Lyon, Centre National de Référence des Staphylocoques, Lyon, France.

Antimicrobial Agents and Chemotherapy
|June 25, 2014
PubMed

Insights

Beta-lactam antibiotics can induce vancomycin resistance in Staphylococcus aureus (h-VISA) strains in vitro. This resistance development requires the trfA gene, suggesting beta-lactams may reduce vancomycin effectiveness against MRSA infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antibiotic Resistance

Background:

  • Glycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus (h-VISA).
  • h-VISA strains have been isolated from patients without prior glycopeptide exposure, such as cystic fibrosis patients receiving beta-lactam treatments.

Purpose of the Study:

  • To investigate whether prolonged exposure to beta-lactam antibiotics can induce h-VISA in methicillin-resistant Staphylococcus aureus (MRSA).

Main Methods:

  • Exposed three clinical vancomycin-susceptible MRSA strains to subinhibitory concentrations of ceftazidime, ceftriaxone, imipenem, and vancomycin for 18 days.
  • Performed population analyses and PCR sequencing to assess vancomycin resistance and identify genetic mutations.
  • Generated a trfA-knockout strain to determine the gene's role in beta-lactam-induced resistance.

Main Results:

  • Seven of 12 derived MRSA strains exhibited h-VISA characteristics after 18 days of beta-lactam exposure.
  • Derived isolates showed thickened cell walls correlated with increased glycopeptide resistance.
  • No de novo mutations in known resistance genes were observed; beta-lactam exposure failed to induce resistance in the trfA-knockout strain.

Conclusions:

  • Subinhibitory concentrations of beta-lactam antibiotics can induce intermediate vancomycin resistance in MRSA in vitro.
  • The induction of vancomycin resistance by beta-lactams is dependent on an intact trfA gene.
  • Prior beta-lactam antibiotic use may compromise vancomycin efficacy in treating MRSA infections.

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