ß-Lactam Resistance Mechanisms of Methicillin-Resistant Staphylococcus aureus

• Published in: The Journal of infectious diseases Vol. 163; no. 3; pp. 514 - 523
• Main Authors: Franciolli, Mario, Bille, Jacques, Glauser, Michel P., Moreillon, Philippe
• Format: Journal Article
• Language: English
• Published: University of Chicago Press 01.03.1991
• Subjects: Antibiotics; Bacteria; Endocarditis; Infections; Major Articles; Medical treatment; Methicillin resistant staphylococcus aureus; Penicillin; Plasmids; Resistance mechanisms; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613

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 ≥64 to 8 µg/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (≥64 µg/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 ≥90% successful amoxicillin treatment of experimental endocarditis due to penicillinasenegative MRSA compared with cloxacillin, which was totally ineffective (P< .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Pfenicillinase-sensitive ß-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.