Rochon-Edouard S, Pestel-Caron M, Lemeland J F, Caron F
Groupe de Recherche sur les Antimicrobiens et les Micro-organismes (GRAM, EA 2656), 76031 Rouen, France.
Antimicrob Agents Chemother. 2000 Nov;44(11):3055-60. doi: 10.1128/AAC.44.11.3055-3060.2000.
Several studies have previously reported synergistic effects between vancomycin and a given beta-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a beta-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different beta-lactam-vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1. 096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the beta-lactam-vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and heterogeneously resistant to methicillin.
此前已有多项研究报道了万古霉素与特定β-内酰胺类药物或特定氨基糖苷类药物联合使用对耐甲氧西林金黄色葡萄球菌（MRSA）菌株具有协同作用。我们研究的目的是全面比较β-内酰胺类药物、万古霉素和/或氨基糖苷类药物的不同组合对32株具有不同氨基糖苷类药物敏感性模式的临床MRSA菌株的作用。首先使用纸片扩散筛选法研究了26种不同的β-内酰胺类药物-万古霉素组合和8种不同的氨基糖苷类药物-万古霉素组合的效果。与万古霉素相互作用最佳的是亚胺培南、头孢唑林或奈替米星。通过棋盘法研究，亚胺培南-万古霉素和头孢唑林-万古霉素对22株菌株均产生协同抑菌作用；亚胺培南-万古霉素和头孢唑林-万古霉素的平均分数抑菌浓度（FIC）指数分别为0.35和0.46。万古霉素-奈替米星组合对所有32株受试菌株均无明显作用；FIC指数平均值为1.096。计算FIC指数时所使用的亚胺培南、头孢唑林、奈替米星和万古霉素的平均浓度在临床上是可以达到的。然后使用亚胺培南、头孢唑林、奈替米星和万古霉素在其最低抑菌浓度（MIC）的一半浓度下单独及以不同组合对10株菌株进行杀菌实验。万古霉素-奈替米星方案很少具有杀菌作用，即使是对奈替米星敏感的菌株也是如此。亚胺培南-万古霉素和头孢唑林-万古霉素组合分别对6株和5株菌株具有强效杀菌作用。添加奈替米星显著增强了头孢唑林或亚胺培南加万古霉素组合的杀菌活性，但仅对β-内酰胺类药物-万古霉素组合无杀菌作用的MRSA菌株有效。值得注意的是，后一类菌株对奈替米星敏感且对甲氧西林呈异质性耐药。
