Enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin in combination against methicillin-resistant Staphylococcus aureus studies by checkerboard MIC method and disc diffusion method using discs containing both drugs

Antimicrobial activities of cefmetazole (CMZ) and cefazolin (CEZ) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-sensitive and 47 methicillin-resistant 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 individually against 9 methicillin-sensitive strains (MSSA) were 0.78-1.56 micrograms/ml and 0.39-0.78 micrograms/ml without 4% NaCl, and 1.56-3.13 micrograms/ml and 0.39-0.78 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, the MICs of CMZ and CEZ against these MSSA decreased to 0.012-0.39 micrograms/ml and 0.10-0.20 micrograms/ml without 4% NaCl, and 0.20-0.78 micrograms/ml and 0.20-0.39 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.385 to 1.013. Minimum FIC indexes < or = 0.5 were seen in 7 out of 9 strains. MICs of CMZ and CEZ individually against 47 methicillin-resistant strains (MRSA) were 3.13-100 micrograms/ml and 3.13-400 micrograms/ml without 4% NaCl, and 6.25-50 micrograms/ml and 50-400 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, MICs of these drugs against MRSA were reduced to 0.10-50 micrograms/ml and 0.39-200 micrograms/ml without addition of 4% NaCl and 0.39-12.5 micrograms/ml and 3.13-100 micrograms/ml with 4% NaCl, respectively. Minimum FIC indexes observed were 0.047 to 0.625, and those with values < or = 0.5 were observed in 43 out of 47 strains. By the disc diffusion method, between the CMZ disc and CEZ disc, a synergistic interaction against MRSA was well observed. In addition, discs containing 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 (20 micrograms/10 micrograms), 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 co