Abstract

We report 570 carbapenemase-producing Klebsiella pneumoniae (CPKP) clinical isolates in a 1,040-bed Greek tertiary hospital during 2004 to 2010. The first CPKP (VIM-producing) was isolated in September 2004. Despite initial containment, VIM producers have become endemic since 2006. KPC-producing K. pneumoniae was first isolated in August 2007 from a patient who came from Israel, spread rapidly, and outcompeted VIM. Overall, 267 (47%) VIM-producing and 301 (53%) KPC-producing strains were isolated, including 141 (24.7%) from patients with bacteraemia. Two isolates carrying both VIM and KPC were isolated in two consecutive months in 2009, but not since. The prevalence of CPKP increased from 0% in 2003 to 38.3% in 2010 (p<0.0001). All genotyped KPC producers harboured blaKPC-2 and belonged to two clones, among which the hyperepidemic Greek clone, related to those from the United States and Israel, predominated. Most metallo-beta-lactamase (MBL) producers carried the blaVIM-1 gene and belonged to several clones, whereas all but one isolate with blaVIM-12 were clustered within a five-month period, arising from one clone. Resistance to non-beta-lactam antibiotics was also increased among CPKP. They were almost invariably resistant to ciprofloxacin and trimethoprim-sulfamethoxazole. Resistance to colistin increased from 3.5% (4/115) in 2008 to 20.8% (25/120) in 2010, and resistance to tigecycline also increased. Following reinforcement of infection control measures, prevalence of CPKP (mainly KPC) has been reduced since mid-2009 (from 46% in 2009 to 38.3% in 2010). In view of the exhaustion of available therapies, investment in infection control resources and optimal antibiotic use is urgently required.

Highlights

  • Carbapenems are important therapeutic agents for treating infections caused by multi-drug resistant Gram-negative bacteria

  • Carbapenemase-producing K. pneumoniae (CPKP) were isolated in all departments and 46.1% of isolates derived from two units: the eight-bed intensive care unit (ICU) (154 isolates; 27.0%) and the 10-bed organ transplant unit (109 isolates; 19.1%)

  • The first CPKP was isolated in September 2004 from an infected wound of a patient who had been transferred from the ICU to the orthopedic ward; The minimum inhibitory concentration (MIC) of imipenem and meropenem were 4 and 2 mg/L, respectively

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Summary

Introduction

Carbapenems are important therapeutic agents for treating infections caused by multi-drug resistant Gram-negative bacteria. Their efficacy, is threatened by the emergence of resistant isolates. Other mechanisms of resistance to carbapenems include the combination of extended spectrum beta-lactamase (ESBL) production with porin changes and/or upregulated efflux pumps (the latter common among carbapenemresistant Pseudomonas aeruginosa) [3,4]. The most prevalent carbapenemases are the molecular class B metallo-beta-lactamases (MBLs), mainly of VIM- and IMP-type, and the (class A) K. pneumoniae-carbapenemases (KPCs) [5]. Carbapenemase-producing K. pneumoniae (CPKP) have been isolated worldwide, including most European countries [8]; CPKP are nowadays endemic in Greece (both VIM and KPC) and Israel (KPC). The presence of KPC in Israel was first reported in 2005 [9] and in Greece in 2007 [10]

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