Wareham David W, Bean David C
Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
Ann Clin Microbiol Antimicrob. 2006 Apr 21;5:10. doi: 10.1186/1476-0711-5-10.
Acinetobacter baumannii has emerged as a major nosocomial pathogen worldwide. Many of the circulating strains exhibit multi-drug resistance remaining consistently susceptible only to polymyxins. In-vitro studies have reported that polymyxins combined with carbapenems, rifampicin or azithromycin are synergistic against these strains despite in-vitro resistance to these agents alone. The use of antimicrobial combinations have therefore been advocated for the treatment of severe A. baumannii infection in man. In order to determine whether such combinations are synergistic against the prevalent clones of multi-drug resistant A. baumannii causing infection in the UK, we performed synergy testing against representative isolates using two rapid Etest methods.
The activity of polymyxin in combination with imipenem, azithromycin or rifampicin was assessed against five strains of multi-drug resistant A. baumannii encoding OXA-23 carbapenemases. Synergy studies were performed by Etest-agar dilution and a combined Etest strip method. Synergy was defined as a FICI of < or = 0.5.
All strains were resistant to beta-lactams, carbapenems, quinolones and aminoglycosides but susceptible to polymyxins. Marked synergy was not seen with polymyxin in combination with imipenem, rifampicin or azithromycin against any of the strains. Borderline synergy (FICI = 0.5) was seen against one strain belonging to OXA-23 clonal group 2, using the Etest-agar dilution method only.
In-vitro synergy with polymxyin in combination with imipenem, rifampicin or azithromycin is highly strain and method dependent. As reliable synergy could not be demonstrated against the prevalent UK multi-drug resistant strains, use of such combinations should not be used for empirical treatment of these infections in the UK. The optimal treatment for serious multi-drug A. baumannii infection and the role of combination therapy should be addressed in a prospective clinical trial.
鲍曼不动杆菌已成为全球主要的医院病原体。许多流行菌株表现出多重耐药性，仅对多粘菌素始终保持敏感。体外研究报告称，尽管这些菌株单独对碳青霉烯类、利福平或阿奇霉素耐药，但多粘菌素与它们联合使用时对这些菌株具有协同作用。因此，有人主张使用抗菌药物联合治疗人类严重鲍曼不动杆菌感染。为了确定这种联合用药对在英国引起感染的多重耐药鲍曼不动杆菌流行克隆是否具有协同作用，我们使用两种快速Etest方法对代表性分离株进行了协同试验。
评估了多粘菌素与亚胺培南、阿奇霉素或利福平联合使用对五株编码OXA - 23碳青霉烯酶的多重耐药鲍曼不动杆菌的活性。通过Etest琼脂稀释法和联合Etest试纸条法进行协同研究。协同作用定义为FICI≤0.5。
所有菌株对β - 内酰胺类、碳青霉烯类、喹诺酮类和氨基糖苷类耐药，但对多粘菌素敏感。多粘菌素与亚胺培南、利福平或阿奇霉素联合使用时，对任何菌株均未观察到明显的协同作用。仅使用Etest琼脂稀释法时，在一株属于OXA - 23克隆群2的菌株中观察到临界协同作用（FICI = 0.5）。
多粘菌素与亚胺培南、利福平或阿奇霉素联合使用的体外协同作用高度依赖菌株和方法。由于在英国流行的多重耐药菌株中未证实可靠的协同作用，因此在英国不应将此类联合用药用于这些感染的经验性治疗。严重多重耐药鲍曼不动杆菌感染的最佳治疗方法以及联合治疗的作用应在前瞻性临床试验中探讨。
