In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.
The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.
Kobayashi
S
S
Pharma Research Laboratories, Hoechst Japan Limited, Saitama, Japan.
Arai
S
S
Hayashi
S
S
Sakaguchi
T
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D013211:Staphylococcus aureus / Q000187:drug effects*; D013407:Sulbactam / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D008712:Methicillin; D013407:Sulbactam