Antimicrobial activities of cefmetazole (CMZ)and cefazolin (CEZ) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-sensitive and 47 methicillinresistant strains) using the checkerboard MIC method and the disc diffusion test using Mueller Hinton agar with or without addition of 4% NaCl.
MICs of CMZ and CEZ in dividually against 9 methicillin-sensitive strains (MSSA) were 0.78-1.56μg/ml and 0.39-0.78μg/ml without 4% NaCl,and 1.56-3.13μg/ml and 0.39-0.78μg/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, the MICs of CMZ and CEZ against these MSSA decreased to 0.012-0.39μg/ml and 0.10-0.20μg/ml without 4% NaCl, and 0.20-0.78μg/ml and 0.20-0.39μg/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.385 to 1.013. Minimum FIC indexes≤0.5 were seen in 7 out of 9 strains.
MICs of CMZ and CEZ individually against 47 methicillin-resistant strains (MRSA) were 3.13-100μg/ml and 3.13-400μg/ml without 4% NaCl, and 6.25-50μg/ml and 50-400μg/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, MICs of these drugs against MRSA were reduced to0.10-50μg/ml and 0.39-200μg/ml without addition of 4% NaCl and 0.39-12.5μg/ml and 3.13-100μg/ml with 4% NaCl, respectively. Minimum FIC indexes observed were 0.047 to 0.625, and those with values≤0.5were observed in 43 out of 47 strains.
By the disc dimlsion method, between the CMZ disc and CEZ disc, asynergistic interaction against MRSA was well observed. In addition, discscontaining both drugs showed a greater inhibitory zone diameter than discs containing the equivalent amount of CMZ or CEZ alone.
These in vitro observations reported here suggest that the use of CMZ and CEZ in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection, as well as for surgical prophylaxis.
TherefOre, further study was carried out to assess the synergistic enhancement of antimicrobial activity of CMZ and CEZ in combination using discs containing various amounts of these drugs at various ratios. Using discs containing CMZ/CEZ (20μg/10μg), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CEZ in combination. From inhibitory zone diameters obtained with these combination discs, enhanced MICs of CMZ or CEZ in combination can be assessed.
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