The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

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Auteurs
Date

1998

Type de document
Périmètre
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Source

Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1086/513805

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/9419181

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pissn/0022-1899

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_01E5506D5EBE9

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

Mots-clés 0

Animals; Anti-Bacterial Agents/pharmacology; Bacterial Proteins; Carrier Proteins/analysis; Carrier Proteins/metabolism; Cefamandole/administration & dosage; Cefamandole/pharmacology; Cephalosporins/administration & dosage; Cephalosporins/pharmacology; Endocarditis/drug therapy; Endocarditis/enzymology; Hexosyltransferases; Methicillin Resistance; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase/analysis; Muramoylpentapeptide Carboxypeptidase/metabolism; Penicillin-Binding Proteins; Penicillinase/metabolism; Peptidyl Transferases; Rats; Staphylococcal Infections/drug therapy; Staphylococcal Infections/enzymology; Staphylococcus aureus/drug effects; Staphylococcus aureus/enzymology

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Cephalosporinase Penicillinase Lactamases, Beta

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Y.A. Que et al., « The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus. », Serveur académique Lausannois, ID : 10.1086/513805

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Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.

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