Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.
J Microbiol Immunol Infect. 2017 Dec;50(6):821-830. doi: 10.1016/j.jmii.2015.10.010. Epub 2015 Nov 26.
BACKGROUND/PURPOSE: Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB) and the lack of novel agents. Although recent data suggest that levofloxacin (LVX) may have unique activity against MDR-AB in combination with colistin (CST), further preclinical work is needed.
We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115) of MDR-AB to investigate the in vitro and in vivo efficacy of LVX-CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time-kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied in vitro. A simple invertebrate model (Galleria mellonella) has been used to assess the in vivo activity of antimicrobial therapies.
The LVX-CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624). In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of < 0.5) was observed between CST and LVX in GN0624. The combination had antibiofilm properties on the preformed biofilms of four tested strains and could prevent the emergence of CST-resistant A. baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p < 0.05).
In summary, a synergistic or additive effect between CST and LVX was observed in vitro and in vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones.
背景/目的：由于广泛存在的耐多药鲍曼不动杆菌（MDR-AB）和缺乏新的治疗药物，治疗鲍曼不动杆菌感染具有挑战性。尽管最近的数据表明左氧氟沙星（LVX）与多粘菌素（CST）联合使用可能对 MDR-AB 具有独特的活性，但仍需要进一步的临床前研究。
我们使用鲍曼不动杆菌标准株 ATCC19606、一株 CST 耐药株 AB19606R 和两株 MDR-AB 临床分离株（GN0624 和 GN1115）来研究 LVX-CST 联合治疗的体外和体内疗效。使用微量棋盘法和时间杀伤法进行协同研究。还在体外研究了抗生素对生物膜的抑制活性和突变预防浓度。使用简单的无脊椎动物模型（家蚕）来评估抗菌治疗的体内活性。
LVX-CST 联合治疗对 CST 敏感的临床分离株（GN0624）具有杀菌作用。在棋盘试验中，GN0624 中 CST 和 LVX 之间观察到协同作用（定义为抑制浓度指数分数 < 0.5）。该联合用药对四种测试菌株的已形成生物膜具有抗生物膜特性，并能防止 CST 耐药鲍曼不动杆菌的出现。用致死剂量的鲍曼不动杆菌感染家蚕幼虫，与单独使用 CST 相比，LVX 与 CST 联合使用时幼虫的存活率显著提高（p < 0.05）。
总之，在体外和体内，CST 和 LVX 对 CST 敏感的鲍曼不动杆菌菌株表现出协同或相加作用，尽管对 CST 耐药菌株没有作用。
