Miranda-Novales Guadalupe, Leaños-Miranda Blanca E, Vilchis-Pérez Mariano, Solórzano-Santos Fortino
Unidad de Investigación en Epidemiología Hospitalaria, Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Ann Clin Microbiol Antimicrob. 2006 Oct 12;5:25. doi: 10.1186/1476-0711-5-25.
combinations of drugs has been proposed as an alternative for oxacillin-resistant staphylococci infections, however, limited information about in vitro combinations are available for multi-resistant strains. The objective of this study was to describe the interaction of beta-lactams in combination with vancomycin or amikacin against 26 oxacillin and amikacin-resistant nosocomial Staphylococcus spp. isolates.
activity of dicloxacillin plus amikacin, cephalothin plus amikacin, cephalothin plus vancomycin, imipenem plus vancomycin and vancomycin plus amikacin was evaluated by checkerboard synergy tests and the fractional inhibitory concentration index (FIC) was calculated.
dicloxacillin plus amikacin, and cephalothin plus amikacin were synergistic or partially synergistic in 84.6% and 100% respectively. For nearly half of the isolates the mean concentrations of dicloxacillin, cephalothin and amikacin at which FIC indexes were calculated were achievable therapeutically. Vancomycin plus amikacin had synergistic effect only against two isolates, and partially synergistic in 38.6%. For the combinations vancomycin plus cephalothin and vancomycin plus imipenem the effect was additive in 76.9% and 80.7% respectively.
in this study the checkerboard analysis showed that amikacin in combination with cephalothin or dicloxacillin was synergistic against most of the resistant strains of S. aureus and coagulase-negative Staphylococcus. Vancomycin in combination with a beta-lactam (cephalothin or imipenem) showed additivity. An indifferent effect predominated for the combination vancomycin plus amikacin. Even though a synergistic effect is expected when using a beta-lactam plus amikacin combination, it is possible that the effect cannot be clinically achievable. Careful selection of antimicrobial combinations and initial MICs are mandatory for future evaluations.
联合用药已被提议作为耐苯唑西林葡萄球菌感染的一种替代治疗方法，然而，关于多重耐药菌株体外联合用药的信息有限。本研究的目的是描述β-内酰胺类药物与万古霉素或阿米卡星联合使用对26株耐苯唑西林和耐阿米卡星的医院内葡萄球菌属分离株的相互作用。
通过棋盘法协同试验评估双氯西林加阿米卡星、头孢噻吩加阿米卡星、头孢噻吩加万古霉素、亚胺培南加万古霉素以及万古霉素加阿米卡星的活性，并计算部分抑菌浓度指数（FIC）。
双氯西林加阿米卡星以及头孢噻吩加阿米卡星分别有84.6%和100%表现为协同或部分协同。对于近一半的分离株，计算FIC指数时双氯西林、头孢噻吩和阿米卡星的平均浓度在治疗上是可以达到的。万古霉素加阿米卡星仅对两株分离株有协同作用，38.6%表现为部分协同。对于万古霉素加头孢噻吩以及万古霉素加亚胺培南的联合用药，分别有76.9%和80.7%表现为相加作用。
在本研究中，棋盘法分析表明，阿米卡星与头孢噻吩或双氯西林联合使用对大多数耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌耐药菌株具有协同作用。万古霉素与β-内酰胺类药物（头孢噻吩或亚胺培南）联合使用表现为相加作用。万古霉素加阿米卡星联合用药主要表现为无关作用。尽管使用β-内酰胺类药物加阿米卡星联合用药预期会有协同作用，但临床上可能无法达到这种效果。在未来的评估中，必须谨慎选择抗菌药物联合用药方案并确定初始最低抑菌浓度。
