联合使用抗菌药物对产KPC-2酶肺炎克雷伯菌的影响

Efficacy of synergistic antibiotic combinations against KPC-2 carbapenemase producing Klebsiella pneumoniae strains

目的探讨联合使用抗菌药物对产KPC-2酶肺炎克雷伯菌的体外抗菌效应，寻找有效的组合方案。方法收集2008-2009年分离白浙江大学医学院附属第一医院，宁波李惠利医院、浙江省人民医院、杭州市第一医院、绍兴市第二医院、杭州市第一医院、复旦大学附属华山医院、南京军区总医院等8家医院确证产KPC-2酶的24株肺炎克雷伯菌，采用MLST技术分型，琼脂稀释法测定阿米卡星、米诺环素、业胺培南、阿莫两林／克拉维酸、头孢他啶、美岁培南、庆大霉素、头孢西丁、头孢吡肟、利福平、多黏菌素B、环丙沙星对24株菌株的MIC值，Etest测定替加环素、哌拉西林／三唑巴坦的MIC值。采用棋盘琼脂稀释法测定头孢吡肟联合阿莫西林／克拉维酸、头孢吡肟联合阿米卡星、环阿沙星联合阿米卡星、环内沙星联合头孢吡肟、亚胺培南联合阿米卡星、亚胺培南联合环丙沙星、亚胺培南联合多黏菌素B、亚胺培南联合米诺环素、多黏菌素B联合利福平、头孢他啶联合阿莫西林／克拉维酸对菌株的抑菌效果。结果24株产KPC-2酶肺炎克雷伯菌分为5个ST型，其中ST11型是最主蚣的克隆群（15株）．菌株对多黏菌素B、替加环素均敏感，对米诺环素耐药率为4．2％。最佳组合方案为头饱吡肟联合阿莫西林／克批维酸，出现协同作用有19株；其次为亚胺培南联合阿米卡星、头孢他啶联合阿莫西林／克拉维酸，出现协同作朋均为13株。结论产KPC-2酶肺炎克雷伯菌对替加环素、多黏菌素B、米诺环素较敏感，头孢吡肟联合阿莫西林／克拉维酸、亚胺培南联合阿米卡星、头孢他啶联合阿莫四林／克批维酸在体外以协同作用为主，其疗效值得临床进一步观察。

Objective To investigate the synergistic efficacy of different antibiotic combinations against KPC-2 carbapenemase producing Klebsiella pneumoniae strains in vitro and search for effective antibiotic combination. Methods During 2008 - 2009, a total of 24 strains of K. pneumoniae producing KPC-2 carbapenemase were collected from 8 hospitals in the First Affiliated Hospital of Medical School of Zhejiang University, Ningbo LiHuiLi Hospital, Zhejiang People＇s Hospital, Hangzhou Third Hospital, the Second Hospital of Shaoxing, Hangzhou First Hospital, Fudan University Huashan Hospital, General Hospital of Nanjing MiLitary Region. MLST technique was used for epidemiologieal analysis. The MIC of antibiotics, such as amikacin, minocycline, imipenem, amoxicilliu/clavulanic-acid, ceftazidime, meropenem, gentamiein, cefoxitin, cefepime, rifampicin, polymyxinB, ciprofloxacin were determined by an agar dilution mefllod, the MIC of tigecycline and piperacillin/tazobactain were determined by Etest. The antibacterial activities of cefepime in combination with amoxicillin/clavulanic-acid, amikacin, or ciprofloxacin, amikacin with ciprofloxacin, irnipenem with amikacin, ciprofloxacin, polymyxinB, or minocycline, polymyxin B with rifampicin, ceftazidime with amoxicillin/clavulanic-aeid were assessed by chequerboard synergy agar dilution tests against all the isolates. Results MLST showed 5 STs among 24 strains of KPC-2 carbapenemase producing K. pneumoniae, and the most prevalent clone was STI 1 （15 strains）. All isolates were susceptible to polymyxin B and tigecycline, and the resistance rate of minocycline was 4. 2% . The synergetic effects were observed in cefepime-amoxicillilv/clavulanic acid, imipenem-amikacin, ceftazidime-amoxicillin/clavulanic acid combinations as 19 isolates, 13 isolates, and 13 isolates, respectively. Conclusions KPC-2 carbapenemase producing K. pneumoniae is sensitive to polymyxin B, tigecycline and minocycline. The synergetic effect is predominant in cefepime-amoxicillin/ clavulanic acid, imipenem-amikacin ceftazidime-amoxicillin/clavulanic acid combinations in vitro, their clinical efficacy are worthy of further observation.