AAC Accepts, published online ahead of print on 18 January 2011 Antimicrob. Agents Chemother. doi:10.1128/aac.01761-10 Copyright 2011, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. 1 2 International transfer of NDM-1-producing Klebsiella 3 pneumoniae from Iraq to France 4 5 6 7 The carbapenemase NDM-1 has been initially identified in Escherichia and Klebsiella 8 pneumoniae in Sweden from a patient transferred from India (10). Then, it has been identified 9 in many enterobacterial species and isolates from patients in the UK, India and Pakistan (3). 10 In addition, recent reports indicated spread of NDM-1 producers in many different countries 11 including Austria, Australia, Belgium, Canada, Danemark, France, Germany, Kenya, The 12 Netherlands, Norway, Sultanate of Oman, and USA (6-9). Most of these reports indicated a 13 likely source of NDM-1 producers located in the Indian subcontinent with both hospital and 14 community acquisition. However, a detailed analysis of the clinical cases indicated that 15 importation of NDM-1 isolates may have originated also from Balkan countries such as 16 Kosovo, Serbia, Montenegro, Bosnia and Herzegovinia which may constitute an additional 17 reservoir for NDM-1 producers (6).
18 A 22-year-old Iraqi male resident in Baghdad was admitted at the Bicêtre hospital 19 (suburb of Paris) on November 8, 2010, following a direct transfer from Baghdad, Iraq. He 20 had been a victim of the terrorist attack at the Baghdad cathedral, killing over 50 people on 21 October 31 st, 2010. He had a wounded shoulder and was immediately hospitalized at the Ibn 22 Al Nafees hospital of Baghdad where he got operated and stayed for five days. At the Bicêtre 23 hospital, he was screened for multidrug resistant bacteria, including extended-spectrum ß- 24 lactamase (ESBL) and carbapenemase producers, methicillin resistant Staphylococcus aureus, 25 and glycopeptide resistant enterococci. Rectal swabs grew only onto ChromID ESBL culture 26 media (biomérieux, La Balme-les-Grottes, France) (5). K. pneumoniae isolate IBN was 27 obtained that showed resistance or decreased susceptibility to all ß-lactams including 28 carbapenems (MICs of imipenem, ertapenem, doripenem, and meropenem being respectively 29 at 2, 8, 2, and 3 µg/ml) according to the CLSI updated guidelines (4). It was resistant also to 30 gentamicin, kanamycin, tobramycin, sulfonamides, rifampin, chloramphenicol, and 31 fluoroquinolones, and remained susceptible to amikacin and fosfomycin, MICs of tigecycline 32 and colistin being respectively at 0.25 and 0.5 µg/ml. The patient did not develop any 33 infection while hospitalized in France. He was neither treated with antibiotics nor
34 decontaminated (actually not recommended for carriage of multidrug resistant 35 Enterobacteriaceae). 36 PCR, sequencing and plasmid analysis revealed that K. pneumoniae IBN harbored the 37 bla NDM-1 carbapenemase gene, in addition to a bla CTX-M-15 ESBL gene both located on 38 different plasmids (100 and 160 kb in size respectively). Screening for additional ß-lactamase 39 genes and for 16S RNA methylase genes as reported (9) showed that K. pneumoniae IBN was 40 co-harboring the bla SHV-11 and bla OXA-1 gene but no 16S RNA methylase gene was identified. 41 Multilocus sequence typing was performed as described worldwide (1) to evidence a possible 42 link with other NDM-1-producing K. pneumoniae recently identified, and results analyzed by 43 eburst (http://pubmlst.org). It showed that isolate IBN belonged to the ST147 sequence 44 type, whereas the NDM-1-positive K. pneumoniae 05-506 index strain and K. pneumoniae 45 isolates recovered in India and in Sultanate of Oman belonged to the ST14 type, both types 46 differing significantly (2, 7). Interestingly, the only report of ST147-type K. pneumoniae so 47 far corresponds to a clonal spread that has been identified in Hungary (2). This Hungarian 48 ST147 clone was susceptible to carbapenems, but it harbored a bla CTX-M-15 plasmid and was 49 resistant to fluoroquinolones (2), as observed for isolate IBN from Iraq. It may be therefore 50 speculated that these isolates could be clonally-related.
51 Considering that one of the two NDM-1-producing K. pneumoniae isolates previously 52 identified from Oman could not be traced back to the Indian subcontinent, this report provides 53 an additional clue that Middle East might be also a reservoir for NDM-1 producers. This 54 result shall be taken in account when taking care of any civilian or soldier hospitalized in Iraq 55 and transferred abroad. It suggests also that spread of NDM-1 producers is already much 56 wider as suspected. Finally, it strenghtens the value of systematic screening for multidrug 57 resistant bacteria for preventing development of nosocomial outbreaks of carbapenem- 58 resistant Enterobacteriaceae as recommended (6). 59 60 Acknowledgments This work was funded by the INSERM U914, France. 61 62 63 64 65 66 67 68 Laurent Poirel Nicolas Fortineau Patrice Nordmann* Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine et Université Paris-Sud, K.-Bicêtre, France 69 70 71 72 *Corresponding author. Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail: nordmann.patrice@bct.aphp.fr
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