Coagulase-negative staphylococci resistant to beta-lactam antibiotics in vivo produce penicillin-binding protein 2a.
Strains of coagulase-negative staphylococci were tested for in vivo resistance in a rabbit model of prophylaxis of endocarditis. Regimens of nafcillin, cefazolin, cefamandole, and vancomycin were compared for efficacy in the prevention of infection caused by two methicillin-resistant strains and a susceptible strain. For the two resistant strains, vancomycin was the most effective drug tested. All regimens were effective against the susceptible strain. The two strains for which prophylaxis with beta-lactam antibiotics failed produced a beta-lactam antibiotic-inducible penicillin-binding protein (PBP) that comigrated in sodium dodecyl sulfate-polyacrylamide gels with the low-affinity PBP 2a that is associated with methicillin resistance in strains of Staphylococcus aureus. Like PBP 2a, this PBP had low binding affinity for beta-lactam antibiotics. Peptide maps after either V8 protease or chymotrypsin digestion of radiolabeled PBP 2a or silver-stained preparations were virtually identical to one another and to maps of PBP 2a from a heterogeneous and a homogeneous strain of S. aureus. Methicillin resistance in coagulase-negative staphylococci and therapeutic failure with beta-lactam antibiotics in vivo is associated with production of PBP 2a, which appears to be highly conserved structurally among different species of staphylococci.
Chambers
H F
HF
Medical Service, San Francisco General Hospital, California 94110.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D003030:Coagulase / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004697:Endocarditis, Bacterial / Q000382:microbiology / Q000517:prevention & control; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis*; D046915:Penicillin-Binding Proteins; D010449:Peptide Mapping; D010458:Peptidyl Transferases; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate; D013050:Spectrometry, Fluorescence; D013210:Staphylococcus / Q000187:drug effects* / Q000201:enzymology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003030:Coagulase; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D012967:Sodium Dodecyl Sulfate; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase