Deveci Aydin, Coban Ahmet Yilmaz, Acicbe Ozlem, Tanyel Esra, Yaman Gorkem, Durupinar Belma
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
J Chemother. 2012 Oct;24(5):247-52. doi: 10.1179/1973947812Y.0000000029.
Treatment of multidrug resistant (MDR) Acinetobacter baumannii infections causes some problems as a result of possessing various antibacterial resistance mechanisms against available antibiotics. Combination of antibiotics, acting by different mechanisms, is used for the treatment of MDR bacterial infections. It is an important factor to determine synergy or antagonism between agents in the combination for the constitution of effective therapy. The study aimed to determine In vitro interactions interpreted according to calculated fractional inhibitory concentration (FIC) index between sulbactam and ceftazidime, ceftriaxone, cefepime, ciprofloxacin, gentamicin, meropenem, tigecycline, and colistin. Ten clinical isolates of A. baumannii were tested for determination of synergistic effects of sulbactam with different antimicrobial combinations. Minimal inhibitory concentration (MIC) values of both sulbactam and combined antibiotics decreased 2- to 128-fold. Synergy and partial synergy were determined in combination of sulbactam with ceftazidime and gentamicin (FIC index: ≤ 0.5 or >0.5 to <1) and MIC values of both ceftazidime and gentamicin for five isolates fell down below the susceptibility break point. Similarly, MIC value of ciprofloxacin for six ciprofloxacin resistant isolates was determined as below the susceptibility break point in combination. However, all isolates were susceptible to colistin and tigecycline, MIC values of both were decreased in combination with sulbactam. Although synergistic and partial synergistic effects were observed in the combination of sulbactam and ceftriaxone, all isolates remained resistant to ceftriaxone. The effect of cefepime-sulbactam combination was synergy in five, partial synergy in one and indifferent in four isolates. Meropenem and sulbactam showed a partial synergistic effect (FIC index: >0.5 to <1) in three, an additive effect (FIC index: 1) in one and an indifferent effect (FIC index: >1-2) in six isolates. Antagonism was not determined in any combination for clinical A. baumannii isolates in the study. In conclusion, sulbactam is a good candidate for combination treatment regimes for MDR A. baumannii infections.
由于多重耐药鲍曼不动杆菌对现有抗生素具有多种抗菌耐药机制,其感染的治疗存在一些问题。作用机制不同的抗生素联合使用,用于治疗多重耐药菌感染。确定联合用药中各药物之间的协同或拮抗作用是构成有效治疗的一个重要因素。本研究旨在根据计算得到的分数抑菌浓度(FIC)指数,确定舒巴坦与头孢他啶、头孢曲松、头孢吡肟、环丙沙星、庆大霉素、美罗培南、替加环素和多粘菌素之间的体外相互作用。对10株鲍曼不动杆菌临床分离株进行检测,以确定舒巴坦与不同抗菌药物联合使用的协同效应。舒巴坦及联合使用的抗生素的最低抑菌浓度(MIC)值均降低了2至128倍。舒巴坦与头孢他啶和庆大霉素联合使用时确定有协同和部分协同作用(FIC指数:≤0.5或>0.5至<1),5株分离株的头孢他啶和庆大霉素的MIC值均降至药敏折点以下。同样,6株对环丙沙星耐药的分离株在联合使用时,环丙沙星的MIC值被确定为低于药敏折点。然而,所有分离株对多粘菌素和替加环素敏感,二者与舒巴坦联合使用时MIC值均降低。虽然舒巴坦与头孢曲松联合使用观察到协同和部分协同作用,但所有分离株对头孢曲松仍耐药。头孢吡肟-舒巴坦联合用药在5株分离株中表现为协同作用,1株为部分协同作用,4株为无关作用。美罗培南和舒巴坦在3株分离株中表现为部分协同作用(FIC指数:>0.5至<1),1株为相加作用(FIC指数:1),6株为无关作用(FIC指数:>1至2)。本研究中临床鲍曼不动杆菌分离株的任何联合用药均未确定有拮抗作用。总之,舒巴坦是多重耐药鲍曼不动杆菌感染联合治疗方案的良好选择。