Kobayashi S, Arai S, Hayashi S, Sakaguchi T
Pharma Research Laboratories, Hoechst Japan Limited, Saitama, Japan.
Antimicrob Agents Chemother. 1989 Mar;33(3):331-5. doi: 10.1128/AAC.33.3.331.
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.
测定了β-内酰胺类药物与两种β-内酰胺酶抑制剂舒巴坦和克拉维酸联合使用对22株耐甲氧西林金黄色葡萄球菌临床分离株的体外抗菌效果。头孢匹罗、头孢噻肟和头孢唑林与舒巴坦（10微克/毫升）联合使用对70%以上的菌株显示出协同作用。甲氧西林和青霉素G与舒巴坦联合使用分别对50%和68%的菌株显示出协同作用，而头孢替安、拉氧头孢、氟氧头孢和头孢美唑与舒巴坦联合使用时，显示出协同作用的菌株仅占40%或更少。克拉维酸仅在与青霉素G联合使用时具有协同作用，其作用可能归因于抑制剂对β-内酰胺酶的抑制。舒巴坦并不能提高β-内酰胺类药物对甲氧西林敏感金黄色葡萄球菌菌株的抗菌活性。在42℃时，头孢噻肟、甲氧西林和氟氧头孢单独使用时的最低抑菌浓度（MIC）较35℃时的值显著降低，且这些β-内酰胺类药物与舒巴坦之间未出现协同作用。42℃孵育并未抑制对青霉素G的耐药性，青霉素G与舒巴坦和克拉维酸联合使用显示出协同作用。β-内酰胺酶的产生量与β-内酰胺类药物MIC的降低无关，但青霉素G与舒巴坦联合使用除外。克拉维酸的β-内酰胺酶抑制活性略强于舒巴坦。这些结果表明，舒巴坦与除青霉素G外的β-内酰胺类药物之间的协同作用可能并非由于β-内酰胺酶抑制，而是基于其他因素对耐甲氧西林金黄色葡萄球菌特异性耐药性的抑制。
