Coagulase-negative staphylococci resistant to beta-lactam antibiotics in vivo produce penicillin-binding protein 2a

H F Chambers1

  • 1Medical Service, San Francisco General Hospital, California 94110.

Insights

Vancomycin effectively treated infections from methicillin-resistant coagulase-negative staphylococci in rabbits. Beta-lactam antibiotic failure in these resistant strains was linked to a conserved penicillin-binding protein (PBP) 2a.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Coagulase-negative staphylococci (CoNS) are significant pathogens, particularly in healthcare settings.
  • Antibiotic resistance in CoNS, especially methicillin resistance, poses a therapeutic challenge.
  • Endocarditis prophylaxis models are crucial for evaluating antibiotic efficacy.

Purpose of the Study:

  • To assess the in vivo efficacy of various antibiotics for endocarditis prophylaxis against CoNS.
  • To investigate the mechanism of beta-lactam antibiotic resistance in CoNS.
  • To compare the effectiveness of nafcillin, cefazolin, cefamandole, and vancomycin.

Main Methods:

  • A rabbit model of endocarditis prophylaxis was employed.
  • Antibiotic regimens included nafcillin, cefazolin, cefamandole, and vancomycin.
  • Infection prevention was tested against two methicillin-resistant CoNS strains and one susceptible strain.
  • Penicillin-binding protein (PBP) analysis was performed using SDS-PAGE and peptide mapping.

Main Results:

  • Vancomycin demonstrated the highest efficacy against the two methicillin-resistant CoNS strains.
  • All tested antibiotic regimens were effective against the susceptible CoNS strain.
  • Resistant strains producing a specific PBP (penicillin-binding protein 2a) showed failure with beta-lactam antibiotics.
  • This inducible PBP 2a exhibited low affinity for beta-lactam antibiotics and was structurally conserved.

Conclusions:

  • Vancomycin is a viable option for prophylaxis against methicillin-resistant CoNS endocarditis.
  • The production of PBP 2a is associated with beta-lactam antibiotic resistance and therapeutic failure in CoNS.
  • PBP 2a is a conserved protein across staphylococcal species, suggesting a common resistance mechanism.

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