Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
J Microbiol Immunol Infect. 2013 Apr;46(2):89-95. doi: 10.1016/j.jmii.2012.03.009. Epub 2012 May 7.
The combination of fusidic acid and rifampicin has a demonstrated synergistic effect against methicillin-resistant Staphylococcus aureus (MRSA), including planktonic and biofilm-related organisms. However, the in vitro efficacy of other combinations of oral anti-MRSA antibiotics in biofilm models has not been established.
The antibacterial activity of fusidic acid, linezolid, rifampicin, and minocycline against 33 biofilm-embedded MRSA isolates in low susceptibility and high resistance breakpoint concentrations was investigated using the 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium-bromide staining method. The compounds were further examined to determine their antibacterial efficacies in combination. The optical density ratio (ODr) was used to evaluate the antibacterial effects of these antibiotics, and the results indicate higher survival rates of MRSA on biofilm. A biofilm-positive phenotype (determined using the crystal violet stain) was defined as an optical density ≥ 0.17 at 492 nm, and strong biofilm formation was defined as an optical density ≥ 1.0.
One-third of the MRSA isolates demonstrated weak biofilm formation, and two-thirds demonstrated strong biofilm formation. At low concentrations, linezolid alone lowered the ODr to 0.55 and was effective against biofilm-embedded MRSA (p < 0.001). The activity of minocycline was concentration-dependent and more effective against MRSA isolates that demonstrated weak biofilm formation. The effect of minocycline seems to be further enhanced when used in combination with either fusidic acid or linezolid at low concentrations, with the obtained results equal to those obtained with rifampicin-based regimens (p < 0.001). Rifampicin plus minocycline was also effective against MRSA in biofilm.
In comparison with monotherapy, minocycline-based combinations exhibit highly effective bactericidal effects against biofilm-embedded MRSA.
夫西地酸和利福平联合使用对耐甲氧西林金黄色葡萄球菌（MRSA）具有协同作用，包括浮游生物和生物膜相关生物。然而，其他口服抗 MRSA 抗生素在生物膜模型中的组合的体外疗效尚未确定。
使用 3-[4,5-二甲基-2-噻唑基]-2,5-二苯基-2H-四唑溴化物染色法，研究了夫西地酸、利奈唑胺、利福平、米诺环素对 33 株低敏感性和高耐药折点浓度下生物膜包埋的 MRSA 分离株的抗菌活性。进一步检查了这些化合物的联合抗菌效果。使用光密度比（ODr）评估这些抗生素的抗菌效果，结果表明 MRSA 在生物膜上的存活率更高。生物膜阳性表型（通过结晶紫染色确定）定义为 492nm 处的吸光度≥0.17，强生物膜形成定义为吸光度≥1.0。
三分之一的 MRSA 分离株表现出弱生物膜形成，三分之二表现出强生物膜形成。在低浓度下，利奈唑胺单独将 ODr 降低至 0.55，对生物膜包埋的 MRSA 有效（p<0.001）。米诺环素的活性呈浓度依赖性，对表现出弱生物膜形成的 MRSA 分离株更有效。当在低浓度下与夫西地酸或利奈唑胺联合使用时，米诺环素的作用似乎进一步增强，获得的结果与基于利福平的方案相当（p<0.001）。利福平加米诺环素也对生物膜中的 MRSA 有效。
与单药治疗相比，米诺环素为基础的联合治疗对生物膜包埋的 MRSA 具有高度有效的杀菌作用。
