Infection Control Unit, Hospital Israelita Albert Einstein, Av, Albert Einstein, 627/701 6º Andar Bloco D, São Paulo, ZIP 05652-000, Brazil.
BMC Infect Dis. 2013 Feb 11;13:80. doi: 10.1186/1471-2334-13-80.
Healthcare-associated infections caused by Klebsiella pneumoniae isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among K. pneumoniae isolated from patients at a tertiary private hospital that showed a phenotype compatible with carbapenemase production although this group of enzymes was not detected in any sample. The aim of this study was to describe the epidemiology and clinical outcomes associated with carbapenem-resistant K. pneumoniae and to determine the antimicrobial resistance mechanisms.
Risk factors associated with carbapenem-resistant K. pneumoniae infections were investigated by a matched case-control study from January 2006 through August 2008. A cohort study was also performed to evaluate the association between carbapenem resistance and in-hospital mortality. Bacterial identification and antimicrobial susceptibility were determined by Vitek 2 and Etest. Carbapenemase activity was detected using spectrophotometric assays. Production of beta-lactamases and alterations in genes encoding K. pneumoniae outer membrane proteins, OmpK35 and OmpK36, were analyzed by PCR and DNA sequencing, as well as SDS-Page. Genetic relatedness of carbapenem resistant isolates was evaluated by Pulsed Field Gel Electrophoresis.
Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant K. pneumoniae infections compared with those with carbapenem-susceptible K. pneumoniae (50.0% vs 25.7%). The length of central venous catheter use was independently associated with carbapenem resistance in the multivariable analysis. All strains, except one, carried blaCTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed blaGES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected.
The K. pneumoniae multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased K. pneumoniae carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presence of the insertion sequences in the outer membrane encoding genes.
由肺炎克雷伯菌引起的医源性感染正在增加，目前可用的有效抗生素很少。我们观察到，在一家私立三级医院的患者中分离出的肺炎克雷伯菌对碳青霉烯类药物的敏感性降低，尽管在任何样本中都未检测到这组酶，但这些菌株表现出与碳青霉烯酶产生一致的表型。本研究的目的是描述与耐碳青霉烯类肺炎克雷伯菌相关的流行病学和临床结局，并确定其耐药机制。
通过 2006 年 1 月至 2008 年 8 月期间进行的匹配病例对照研究，调查耐碳青霉烯类肺炎克雷伯菌感染的相关危险因素。还进行了一项队列研究，以评估碳青霉烯类耐药与院内死亡率之间的关系。采用 Vitek 2 和 Etest 进行细菌鉴定和药敏试验。使用分光光度法检测碳青霉烯酶活性。通过 PCR 和 DNA 测序以及 SDS-Page 分析β-内酰胺酶的产生以及编码肺炎克雷伯菌外膜蛋白 OmpK35 和 OmpK36 的基因改变。通过脉冲场凝胶电泳评估耐碳青霉烯类分离株的遗传相关性。
本研究共纳入 60 例患者（20 例病例和 40 例对照）。与碳青霉烯类敏感肺炎克雷伯菌感染患者相比，耐碳青霉烯类肺炎克雷伯菌感染患者的死亡率更高（50.0% vs 25.7%）。多变量分析显示，中心静脉导管使用时间与碳青霉烯类耐药独立相关。除 1 株外，所有菌株均携带 blaCTX-M-2，一种扩展谱β-内酰胺酶基因。此外，仅有 1 株还携带 blaGES-1。未检测到编码质粒介导的 AmpC 内酰胺酶或碳青霉烯酶（KPC、金属β-内酰胺酶或 OXA-碳青霉烯酶）的基因。
多药耐药的肺炎克雷伯菌与显著的死亡率相关。肺炎克雷伯菌对碳青霉烯类药物敏感性降低的机制可能与头孢菌素酶的存在以及外膜编码基因中插入序列导致孔蛋白改变有关。
