JAC Advance Access published online on December 6, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm471
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Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae producing the carbapenem-hydrolysing VIM-1 metallo-β-lactamase: first Italian outbreak
1 Di.S.C.A.T., Microbiology Unit, University of Genoa, Genoa, Italy 2 Department of Molecular Biology, Microbiology Unit, University of Siena, Siena, Italy 3 Department of Infectious Diseases, S. Martino Hospital, Genoa, Italy 4 Department of Anaesthesiology—Critical Care, S. Martino Hospital, Genoa, Italy
Received 28 August 2007; returned 23 September 2007; revised 9 November 2007; accepted 13 November 2007
* Corresponding author. Tel: +39-010-3537502; Fax: +39-010-3537655; E-mail: anna.marchese{at}unige.it
Objectives: To investigate the first Italian outbreak of bloodstream infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae producing metallo-β-lactamase (MBL), which occurred in three wards of one large tertiary-care hospital in Genoa, Italy, from September 2004 to March 2005.
Methods: MBL production was screened by an imipenem–EDTA disc synergy test and confirmed by a conventional hydrolysis test. Antibiotic susceptibility was determined by broth microdilution or disc diffusion. PFGE was used to study the genetic relatedness of isolates. PCR and sequencing were carried out to identify the β-lactamase genes and to analyse the genetic context of the MBL gene. Outer membrane protein (OMP) profiles were analysed by SDS–PAGE.
Results: Nine cases of bloodstream infections caused by an MDR strain of K. pneumoniae producing the VIM-1 MBL and the SHV-5 extended-spectrum β-lactamase (ESBL) were identified. The isolates exhibited various carbapenem resistance levels (imipenem MICs ranged from 4 to 64 mg/L) and were resistant to other β-lactams, fluoroquinolones, trimethoprim/sulfamethoxazole and chloramphenicol. The isolate with the highest imipenem MIC also lacked the k36 OMP. The blaVIM-1 gene cassette was part of the variable region of a class 1 integron that also included an aac(6')-IIc cassette. The ESBL and MBL genes were transferable by conjugation.
Conclusions: This is the first report on the emergence of an MDR strain of K. pneumoniae producing the VIM-1 MBL, causing an outbreak of bloodstream infections in an Italian hospital. The strain evolved through OMP alterations generating a mutant with increased carbapenem resistance.
Key Words: carbapenem resistance , carbapenemases , extended-spectrum β-lactamases , class 1 integrons
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