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

Détails

Ressource 1Télécharger: serval:BIB_01E5506D5EBE.P001 (196.18 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
ID Serval
serval:BIB_01E5506D5EBE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.
Périodique
Journal of Infectious Diseases
Auteur(s)
Que Y.A., Entenza J.M., Francioli P., Moreillon P.
ISSN
0022-1899 (Print)
ISSN-L
0022-1899
Statut éditorial
Publié
Date de publication
1998
Volume
177
Numéro
1
Pages
146-154
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/04/2008 8:46
Dernière modification de la notice
25/09/2019 7:08
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