SYNERGISTIC ACTIVITY OF FLOMOXEF AND CEFAMANDOLE AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

• Published in: CHEMOTHERAPY Vol. 39; no. 10; pp. 968 - 975
• Main Authors: Kobayashi, Yoshinao, Sonobe, Naomi, Doi, Masayoshi, Murakami, Kazuhisa, Yoshida, Tadashi
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1991
• Subjects: cefamandole; flomoxef
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.39.968

In vitro antibacterial activity of the combination of flomoxef (FMOX) and cefamandole (CMD) against methicillin-resistant Staphylococcus aureus (MRSA) was evaluated by checkerboard dilution method. The combination showed synergistic activity against 181 (95%) of 190 MRSA strains with a minimal fractional inhibitory concentration (FIC) of less than 0.5. Furthermore, the MICs of both antibiotics were less than 1.6μg/ml against 65 % of strains when administered in combination. Removal of the 7 α-methoxy substituent from FMOX resulted in diminution of the synergistic effect suggesting that inhibitory action of FMOX against penicillin-binding protein 4 (PBP 4) was involved in its synergistic effect because 7 α-methoxy conferred on the compound an affinity for PBP 4. This in vitro synergistic activity was reflected in the therapeutic efficacy of the combination against experimental infections in mice intraperitoneally challenged with MRSA.