Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY:: molecular epidemiology and in vitro activity of polymyxin B and other agents

Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY:: molecular epidemiology and in vitro activity of polymyxin B and other agents
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DOI:
10.1093/jac/dki175
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发表时间:
2005-07-01
影响因子:
5.2
通讯作者:
Landman, D
Landman, D
中科院分区:
医学2区
文献类型:
--
作者:
Bratu, S;Tolaney, P;Landman, D

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目的:描述纽约布鲁克林耐碳青霉烯类肺炎克雷伯菌的分子流行病学,并评估各种抗生素组合的体外活性。方法:2003 年 8 月至 2004 年 6 月,将疑似碳青霉烯类耐药的临床分离株转至中心研究实验室。对分离株进行 MIC 检测、核糖分型,并分析是否存在 KPC 碳青霉烯酶。对选定的分离株进行了使用各种抗生素的时间杀灭研究。结果:从 10 家布鲁克林医院转诊了 96 株分离株。所有分离株均对碳青霉烯类抗生素具有耐药性,其中大多数 MIC > 32 mg/L。很少有人对氟喹诺酮类药物和头孢菌素类药物敏感;大约一半的人对氨基糖苷类药物敏感,90% 对多粘菌素 B 敏感。三分之二的人对多西环素敏感,所有人都被认为对研究中的甘氨酰环素类抗生素替加环素敏感。几乎所有人都拥有 bla(KPC),并且超过 80% 属于一种核糖型。在涉及 16 个分离株的时间杀灭研究中,替加环素表现出抑菌活性和多粘菌素 B 浓度依赖性杀菌活性。 0.5 x MIC 的多粘菌素 B 与利福平的组合对 15/16 分离株(包括两种多粘菌素抗性菌株)具有协同活性。多粘菌素B与亚胺培南联合用药对10/16株有协同杀菌活性,但对3株株有拮抗作用。结论:纽约市多家医院存在bla(KPC)多重耐药肺炎克雷伯菌。体外最稳定的活性药物是替加环素和多粘菌素 B,特别是当后者与利福平联合使用时。这些药物的临床疗效仍有待确定。
Objectives: To describe the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Brooklyn, NY and assess the in vitro activity of various antibiotic combinations.Methods: Clinical isolates with suspected carbapenem resistance were referred to the central research laboratory from August 2003 to June 2004. Isolates underwent MIC testing, ribotyping, and were analysed for the presence of KPC carbapenemases. Time-kill studies using various antibiotic(s) were performed on selected isolates.Results: Ninety-six isolates were referred from 10 Brooklyn hospitals. All isolates were resistant to the carbapenems with most having MICs > 32 mg/L. Few were susceptible to fluoroquinolones and cephalosporins; approximately half were susceptible to aminoglycosides, and 90% to polymyxin B. Two-thirds were susceptible to doxycycline, and all were considered susceptible to the investigational glycylcycline antibiotic tigecycline. Virtually all possessed bla(KPC), and over 80% belonged to one ribotype. In time-kill studies involving 16 isolates, tigecycline demonstrated bacteriostatic activity and polymyxin B concentration-dependent bactericidal activity. The combination of polymyxin B at 0.5 x MIC plus rifampicin had synergic activity against 15/16 isolates, including two polymyxin-resistant strains. The combination of polymyxin B plus imipenem had synergic bactericidal activity against 10/16 isolates, but was antagonistic for three isolates.Conclusions: Multiresistant K. pneumoniae with bla(KPC) are present in multiple hospitals in New York City. The most consistently active agents in vitro were tigecycline and polymyxin B, particularly when the latter was combined with rifampicin. The clinical efficacy of these agents remains to be determined.