Molecular correlation between in vitro and in vivo activity of beta-lactam and beta-lactamase inhibitor combinations against methicillin-resistant Staphylococcus aureus.
J Lab Clin Med
; 125(2): 200-11, 1995 Feb.
Article
en En
| MEDLINE
| ID: mdl-7844469
ABSTRACT
Beta-Lactam resistance in Staphylococcus aureus is associated with beta-lactamase production, with the presence of a new penicillin binding protein (PBP) called PBP2a, with reduced affinity for beta-lactam antibiotics, and with modifications of normal PBPs. We have studied these mechanisms of resistance, in vivo and in vitro, for several beta-lactam antibiotics against both beta-lactamase-producing and non-producing methicillin-resistant S. aureus organisms (MRSA). Our results showed that all tested agents inhibited binding of labeled penicillin G to many PBPs. The combination of cefoperazone and sulbactam was the best combination, and it inhibited radiolabeled penicillin G binding to PBP2a at a lower concentration than that needed for cefoperazone alone. In vivo, the regimen of cefoperazone plus sulbactam was also more effective than cefoperazone alone. For beta-lactamase-negative strains this correlated with an increased binding affinity of cefoperazone plus sulbactam to PBP2a and PBP4. The improved efficacy of cefoperazone plus sulbactam versus cefoperazone with a beta-lactamase producing strain was closely related to cefoperazone hydrolysis by beta-lactamase that was inhibited by sulbactam. This study demonstrates that there is more than one effect of beta-lactamase inhibitors when they are combined with beta-lactam antimicrobial agents, and also that there may be a role for these agents in therapy for MRSA infections.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Proteínas Bacterianas
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Muramoilpentapéptido Carboxipeptidasa
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Proteínas Portadoras
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Peptidil Transferasas
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Inhibidores de beta-Lactamasas
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Hexosiltransferasas
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Antibacterianos
Límite:
Animals
Idioma:
En
Revista:
J Lab Clin Med
Año:
1995
Tipo del documento:
Article