Article: article from journal or magazin.
Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus.
Journal of Infectious Diseases
In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.
Animals, Anti-Bacterial Agents/metabolism, Anti-Bacterial Agents/pharmacology, Bacterial Proteins/metabolism, Binding, Competitive, Carrier Proteins/metabolism, Drug Resistance, Microbial, Endocarditis, Bacterial/blood, Endocarditis, Bacterial/drug therapy, Female, Hexosyltransferases, Methicillin Resistance, Microbial Sensitivity Tests, Muramoylpentapeptide Carboxypeptidase/metabolism, Penicillin-Binding Proteins, Penicillinase, Peptidyl Transferases, Protein Binding, Rats, Rats, Inbred Strains, Staphylococcal Infections/blood, Staphylococcal Infections/drug therapy, Staphylococcus aureus/drug effects, Staphylococcus aureus/enzymology, beta-Lactams
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