Department of Ophthalmology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Cornea. 2023 Dec 1;42(12):1555-1561. doi: 10.1097/ICO.0000000000003304. Epub 2023 Apr 27.
Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs.
Using a panel of 9 ophthalmic antibiotics, 3 antifungal agents, and 2 antiacanthamoeba therapeutics, fractional inhibitory concentration testing in the standard checkerboard format was used to study 36 antibiotic-antibiotic combinations, 27 antibiotic-antifungal combinations, and 18 antibiotic-antiacanthamoeba combinations against both Staphylococcus aureus and Pseudomonas aeruginosa for synergistic, additive, neutral, or antagonistic drug-drug interactions.
We demonstrate that while most combinations resulted in no change in antimicrobial efficacy of individual components, the combination of erythromycin + polyhexamethylene biguanide was found to be antagonistic toward P. aeruginosa . Conversely, 18 combinations toward S. aureus and 15 combinations toward P. aeruginosa resulted in additive or synergistic activity, including 4 with improved activity toward both species.
Understanding how drug-drug interactions may affect drug efficacy is critical to selecting the appropriate combination therapy and improving clinical outcomes of this blinding disease.
感染性角膜炎是一种严重的疾病，需要立即进行强化、广谱的经验性治疗，以防止视力丧失。鉴于可能导致严重角膜疾病的病原体种类繁多，目前的指南建议同时使用几种抗菌药物进行治疗，以在等待微生物培养结果的同时提供充分的覆盖范围。然而，目前尚不清楚联合使用多种眼用抗菌药物会如何影响个别药物的疗效。
使用一组 9 种眼科抗生素、3 种抗真菌药物和 2 种抗棘阿米巴治疗药物，采用标准棋盘格式的部分抑菌浓度测试法，研究了 36 种抗生素-抗生素组合、27 种抗生素-抗真菌组合和 18 种抗生素-抗棘阿米巴组合对金黄色葡萄球菌和铜绿假单胞菌的协同、相加、中性或拮抗药物相互作用。
我们证明，虽然大多数组合对个别成分的抗菌效果没有改变，但发现红霉素+聚六亚甲基双胍组合对铜绿假单胞菌具有拮抗作用。相反，有 18 种针对金黄色葡萄球菌和 15 种针对铜绿假单胞菌的组合具有相加或协同作用，包括 4 种对两种细菌都具有改善作用的组合。
了解药物相互作用如何影响药物疗效对于选择适当的联合治疗方案和改善这种致盲性疾病的临床结局至关重要。
