The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus
| Autor: | Patrick Francioli, Yok-Ai Que, José-M. Entenza, Philippe Moreillon |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Staphylococcus aureus
Micrococcaceae Penicillin binding proteins Microbial Sensitivity Tests Muramoylpentapeptide Carboxypeptidase medicine.disease_cause Microbiology Bacterial Proteins In vivo medicine Immunology and Allergy Endocarditis Animals Penicillin-Binding Proteins Cefamandole Anti-Bacterial Agents/pharmacology Carrier Proteins/analysis Carrier Proteins/metabolism Cefamandole/administration & dosage Cefamandole/pharmacology Cephalosporins/administration & dosage Cephalosporins/pharmacology Endocarditis/drug therapy Endocarditis/enzymology Hexosyltransferases Methicillin Resistance Muramoylpentapeptide Carboxypeptidase/analysis Muramoylpentapeptide Carboxypeptidase/metabolism Penicillinase/metabolism Peptidyl Transferases Rats Staphylococcal Infections/drug therapy Staphylococcal Infections/enzymology Staphylococcus aureus/drug effects Staphylococcus aureus/enzymology biology Sulbactam biochemical phenomena metabolism and nutrition Penicillinase Staphylococcal Infections biology.organism_classification medicine.disease Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Cephalosporins Infectious Diseases Carrier Proteins medicine.drug |
| Zdroj: | Journal of Infectious Diseases, vol. 177, no. 1, pp. 146-154 |
| ISSN: | 0022-1899 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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