[Enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam in combination against methicillin-susceptible and -resistant Staphylococcus aureus studied using checkerboard MIC method and disc diffusion method with discs containing both drugs].
Antimicrobial activities of cefmetazole (CMZ) and cefotiam (CTM) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-susceptible strains and 47 methicillin-resistant strains) by the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CTM individually against 9 methicillin-susceptible strains (MSSA) were 0.78 approximately 1.56 micrograms and 0.39 approximately 0.78 micrograms/ml without 4% NaCl, and 1.56 approximately 3.13 micrograms/ml and 0.78 approximately 1.56 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CTM, MICs of CMZ and CTM against these MSSA decreased to 0.20 approximately 0.39 micrograms/ml and 0.20 micrograms/ml without 4% NaCl, and 0.20 approximately 0.78 micrograms/ml and 0.10 approximately 0.78 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.313 to 0.628. FIC indexes < or = 0.5 were observed against 7 out of 9 strains. MICs of CMZ and CTM individually against 47 methicillin-resistant strains (MRSA) were 6.25 approximately 100 micrograms/ml and 3.13 approximately 800 micrograms/ml in the absence of 4% NaCl, and 6.25 approximately 100 micrograms/ml and 50 approximately greater than 800 micrograms/ml in the presence of 4% NaCl, respectively. In combination of CMZ and CTM, MICs of these drugs against MRSA were reduced to 0.20 approximately 25 micrograms/ml without 4% NaCl and 0.39 approximately 25 micrograms/ml and 3.13 approximately 200 micrograms/ml with 4% NaCl, respectively. The strains studied showed minimum FIC indexes of 0.02 to 0.5 either with 4% NaCl or not. By the disc diffusion method, between CMZ disc and CTM disc a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone than discs containing the equivalent amount of CMZ or CTM alone. These in vitro observations reported here suggest that the use of CMZ and CTM in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection. Prophylactic use of CMZ and CTM in combination for surgical infection would be also more effective than the use of these drugs individually. The synergistic enhancement of antimicrobial activity of CMZ and CTM in combination was assessed using discs containing various amounts of these drugs at various ratios. In this investigation, discs containing CMZ/CTM (20 micrograms/10 micrograms) was selected. Using discs containing CMZ/CTM (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CTM in combination.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Clinical Investigation, Kitano Hospital, Tazuke Kofukai Medical Research Institute.
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D015311:Cefmetazole / Q000494:pharmacology; D015310:Cefotiam / Q000494:pharmacology; D004058:Diffusion; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests / Q000379:methods*; D013211:Staphylococcus aureus / Q000187:drug effects*
D015311:Cefmetazole; D015310:Cefotiam