Plasmid-mediated carbapenem-hydrolysing  -lactamase KPC-2 in a Klebsiella pneumoniae isolate from Switzerland

Sir, The emergence and dissemination of Enterobacteriaceae isolates producing carbapenemases in various geographical regions represent a significant threat to the management of nosocomial infections. Carbapenem-hydrolysing β-lactamases include metallo-β-lactamases, expanded-spectrum oxacillinases and Ambler class A enzymes.1 Among class A enzymes, the most common are KPC β-lactamases, which hydrolyse all β-lactams except cephamycins. The blaKPC-like genes have been reported most often from enterobacterial species recovered from many states in the USA.2 In addition, KPC-producing Klebsiella pneumoniae isolates are endemic in Greece and Israel, and have been reported from many countries worldwide, including South America, China and Western Europe.2 The rapid dissemination of KPC enzymes among different enterobacterial species is related to the localization of blaKPC genes on transferable broad-host-range plasmids and their association with a particular transposon,3 but is also linked with a disseminated international clone of KPC-producing K. pneumoniae sequence type (ST) 258.4,5 We describe here the first identification of a KPC-producing K. pneumoniae in Switzerland. In mid-2010, a patient with methicillin-resistant Staphylococcus aureus pneumonia requiring mechanical ventilation was transferred from a hospital in Sicily to the Neuchâtel public hospital in Switzerland. During his 11 day stay in hospital in Sicily, he had been treated with ciprofloxacin, clarithromycin and teicoplanin. Upon arrival in Switzerland the patient was febrile and was treated empirically with cefepime and linezolid for 5 days. A week later, while the patient was afebrile, urine and sputum cultures grew a pan-resistant K. pneumoniae. This was considered as colonization, thus no antibiotic treatment was initiated and the patient eventually fully recovered. The antibiogram determined by the disc diffusion method and MICs determined by Etest and the Vitek2 system (AST-EXN8 card) and interpreted according to the CLSI guidelines6 revealed that this K. pneumoniae strain was resistant to all penicillins and expanded-spectrum cephalosporins, imipenem (MIC, 12 mg/L), ertapenem (>32 mg/L), meropenem (32 mg/L) and doripenem (16 mg/L). This strain was of intermediate susceptibility to tigecycline (MIC of 2 mg/L), but was susceptible to gentamicin (MIC of 3 mg/L), and the MIC of colistin was >16 mg/L. A blaKPC-2 gene was identified by PCR and sequencing as previously described.7 The isolate possessed additional β-lactamase genes, including those encoding the narrow-spectrum β-lactamases SHV-11 (naturally occurring), TEM-1 and OXA-9. PCR mapping and sequencing of the blaKPC flanking regions using combinations of primers showed that the blaKPC-2 gene was located inside a Tn4401 transposon identical to that found in the K. pneumoniae reference strain YC from France.3 Multilocus sequence typing (MLST), performed according to the protocol described on the K. pneumoniae MLST web site (http://www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html), showed that this K. pneumoniae strain was of the ST258 type, known to be disseminated worldwide.4,5 The plasmid location of the blaKPC-2 gene was confirmed by electroporation of a crude plasmid extract obtained using the Kieser method into Escherichia coli TOP10.7 Plasmid analysis of the K. pneumoniae isolate and its transformant confirmed that blaKPC-2 was located on an ∼75 kb plasmid. No other antibiotic resistance marker was co-transferred. PCR-based replicon typing of the major plasmid incompatibility groups showed that the blaKPC-2-positive plasmid belonged to the IncFIIAS incompatibility group.7 We believe this is the first report of a KPC-producing isolate of K. pneumoniae from Switzerland. It seems likely that the isolate was imported as a result of the transfer of a patient from Sicily. In Italy, several studies reported KPC-2- or KPC-3-producing K. pneumoniae isolates, being mostly of ST258 type.4,8,9 There is a need for urgent action to slow down and control the worldwide and epidemic spread of enterobacterial carbapenemase producers, including countries with a low level of antibiotic resistance, such as Switzerland. This work was mostly funded by the INSERM (U914), France, and by grants from the Ministère de l'Education Nationale et de la Recherche (UPRES-EA3539), Université Paris XI, France and from the European Community (TROCAR, HEALTH-F3-2008-223031 and TEMPOtest-QC, HEALTH-2009-241742). None to declare.