Eliopoulos G M
Harvard Medical School, Massachusetts.
Infect Dis Clin North Am. 1989 Sep;3(3):399-406.
Among the reasons for use of antimicrobials in combination is the desire to achieve synergistic inhibitory or bactericidal activity. Several methods have been used to test for the presence of synergistic interactions, but virtually all are either very time consuming or nonstandardized. With combinations of cell wall-active agents plus aminoglycosides, bactericidal synergism has been associated with enhanced intracellular uptake of the aminoglycoside. Combinations of beta-lactamase inhibitors with beta-lactams susceptible to enzymatic hydrolysis have yielded synergistic activity against a number of common pathogens. The example of trimethoprim-sulfamethoxazole illustrates the potential value of combination of drugs acting at proximate steps along a single metabolic pathway. By analogy, combinations of antimicrobials active at various steps in peptidoglycan synthesis might also result in synergistic interactions. Use of certain drug combinations does pose the risk, however, of unwanted antagonistic interactions. The clinical importance of synergism in the treatment of bacterial infections has been documented in only a few limited circumstances.
联合使用抗菌药物的原因之一是期望获得协同抑制或杀菌活性。已经使用了几种方法来检测协同相互作用的存在，但几乎所有方法要么非常耗时，要么未标准化。对于细胞壁活性药物与氨基糖苷类药物的联合使用，杀菌协同作用与氨基糖苷类药物细胞内摄取增加有关。β-内酰胺酶抑制剂与易受酶水解的β-内酰胺类药物联合使用，已对多种常见病原体产生协同活性。甲氧苄啶-磺胺甲恶唑的例子说明了作用于单一代谢途径中相邻步骤的药物联合使用的潜在价值。以此类推，在肽聚糖合成的不同步骤具有活性的抗菌药物联合使用也可能产生协同相互作用。然而，使用某些药物组合确实存在产生不良拮抗相互作用的风险。仅在少数有限的情况下，协同作用在治疗细菌感染中的临床重要性得到了证实。
