Importation of OXA-48-producing Klebsiella pneumoniae from Kuwait

Sir, The current emergence of the carbapenem-hydrolysing class D β-lactamase OXA-48 in Enterobacteriaceae is of great concern, since the corresponding gene is encountered in various enterobacterial species that are often multidrug resistant.1 OXA-48 hydrolyses penicillins at high level and carbapenems at low level; however, its impact on carbapenems is significant, especially when combined with additional mechanisms and, in particular, permeability defects.2 The first identification of OXA-48 producers was from Turkey, where it is now considered endemic.1,2 A rapid dissemination of OXA-48 producers has been observed, and North Africa is now being considered as an additional reservoir.1 The spread of the blaOXA-48 gene is linked to the dissemination of an epidemic 62 kb IncL/M-type and self-conjugative plasmid that has been identified in many clonally unrelated strains and different enterobacterial species from distantly located geographic areas.3 Recently the blaOXA-48 gene has been identified in Israel and Lebanon, whereas the blaOXA-181 gene (a blaOXA-48 derivative) has been identified in France, India, The Netherlands and Sultanate of Oman, and the blaOXA-163 (another derivative encoding resistance to broad-spectrum cephalosporins) has been identified in Argentina.1 In Kuwait, the only carbapenemase-producing Enterobacteriaceae so far correspond to two recently identified NDM-1-producing Klebsiella pneumoniae.4 Our study was initiated by the isolation of carbapenem-resistant K. pneumoniae from a diabetic patient who had been hospitalized in July 2011 in Kuwait, where she developed gangrene in her left foot. In August, she was transferred to Paris, France, where her left leg was amputated and she underwent prosthesis surgery. Upon admission at the Paris hospital, a rectal swab was performed to screen for multidrug-resistant bacteria. Selection was performed onto a Drigalski plate on which an imipenem-containing disc had been placed, and onto a ChromID ESBL plate (bioMérieux, La Balme-les-Grottes, France). It grew K. pneumoniae strain ALI showing resistance to carbapenems. No secondary transmission occurred at the Paris hospital following the rapid implementation of strict infection control measures. The antibiogram determined by the disc diffusion method and MICs determined by Etest (Ab bioMérieux, Solna, Sweden) and interpreted according to the CLSI guidelines5 revealed that K. pneumoniae isolate ALI was highly resistant to penicillins and carbapenems, with MICs of ertapenem, imipenem, meropenem and doripenem being >32, 32, 32 and 8 mg/L, respectively. Isolate ALI was fully susceptible to expanded-spectrum cephalosporins, with MICs of ceftazidime and ceftriaxone being 0.5 mg/L. This isolate was susceptible to all quinolones and aminoglycosides, being resistant only to fosfomycin and nitrofurantoin. Multilocus sequence typing (MLST) performed as described previously6 showed that K. pneumoniae ALI belonged to ST743, which is a newly identified sequence type. PCR mapping performed as described previously7 identified the blaOXA-48 gene that was located on the composite transposon Tn1999. Isolate ALI also possessed an intrinsic blaSHV-28 gene encoding a narrow-spectrum β-lactamase of the SHV-1 type. Plasmid location of the blaOXA-48 gene was confirmed by mating-out assays followed by plasmid analysis as described.7 PCR assays using a set of primers designed from the reference blaOXA-48-positive plasmid confirmed that blaOXA-48 was located on the IncL/M-type ∼62 kb epidemic plasmid.3 No other antibiotic resistance marker was co-transferred, as observed previously.3 This study reports on the first OXA-48-producing K. pneumoniae from the Arabian peninsula. That finding is not so surprising considering that recent studies have indicated that North African countries, which represent an important source of the immigrant population of Kuwait, are endemic for OXA-48 producers.1 Such a finding further highlights the current widespread nature of OXA-48 producers, and further legitimates the current policies implemented in France to screen patients for multidrug-resistant isolates who have been hospitalized abroad. This work was supported by a grant from the Ministère de la Recherche, Université Paris XI, Paris and by the INSERM, France. The research leading to these results has also received funding from the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement no. 241742 (TEMPOtest-QC). None to declare. We thank platform Genotyping of Pathogens and Public Health (Institut Pasteur, Paris, France) for coding MLST alleles and profiles and making them available at www.pasteur.fr/mlst.