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ESBL-producing strain of hypervirulent Klebsiella pneumoniae K2, France.

To the Editor: Klebsiella pneumoniae is mainly responsible for hospital-acquired urinary tract infections, bacteremia, pneumonia and intra-abdominal infections. However, since the mid-1980s, K. pneumoniae has also been described as the cause of highly invasive community-acquired infections (1,2). The K. pneumoniae isolates associated with such infections are often hypermucoviscous and frequently belong to the capsular serotypes K1 or K2. Two of the most extensively studied genes associated with invasive infections are a mucoviscosity-associated gene A (magA) in serotype K1 and a regulator of mucoid phenotype A (rmpA). These strains of hypervirulent K. pneumoniae (hvKP) are now circulating worldwide (1,2).

At the same time, a substantial increase of high-level antimicrobial resistance acquired by non-hvKP strains has also been observed. Clonal complexes of hvKP and multi-drug-resistant (MDR) strains had been considered independent (3) until 2014, when extended-spectrum [beta]-lactamase (ESBL)- or carbapenemase-producing hvKP were first identified in China (4). Here we report an ESBL-producing strain of hvKP isolated from a patient in France.

The patient was a 56-year-old woman, born in Algeria, who alternately resided in France and Algeria for several years without travel to any other country. She underwent liver transplant in 2007 for primary biliary cirrhosis. In 2012, she had a routine posttransplant liver biopsy indicating granulomatosis, resulting in several examinations to determine its etiology. The patient was afebrile with no inflammatory syndrome. A thoracic computed tomography scan indicated no abnormalities. We performed a bronchoalveolar lavage, and bacteriologic examination of the specimen indicated a strain of K. pneumoniae with a hypermucoviscosity phenotype. We identified the ESBL phenotype with a positive double-disk synergy test between clavulanic acid and third-generation cephalosporins and aztreonam. We conducted antimicrobial susceptibility tests according to guidelines issued in 2013 by the Comite de l'Antibiogramme de la Societe Frangaise de Microbiologie (http://www.sfm- microbiologie.org/UserFiles/files/casfm/CASFM2013vjuin.pdf). These tests revealed high-level resistance to third-generation cephalosporins and to all aminoglycosides except amikacin. The strain was susceptible to cefoxitin, piperacillin/ tazobactam, carbapenems, all fluoroquinolones, fosfomycin, and trimethoprim/sulfamethoxazole. The patient did not receive any antimicrobial drug treatment and after 3 years of follow-up reported no signs of pneumopathy.

Multiplex PCR and sequencing of the identified strain indicated the presence of blaCTX-M-3 (5). We extracted plasmid carrying the ESBL gene with the DNA Plasmid Miniprep Kit (QIAGEN, Valencia, CA, USA) and transferred the gene by electroporation into Escherichia coli DH10B cells. Relaxase typing, which detects major replicon groups, revealed only IncL/M plasmid (6). We performed another multiplex PCR to determine capsular serotypes K1 or K2 and the presence of major virulence factors. The capsular serotype was K2 (7). We identified rmp A, the plasmid-mediated gene regulating extracellular polysaccharide synthesis, and iutA, entB, mrkD, andybtS genes by this PCR test. The isolate belonged to sequence type (ST) 86 as determined by multilocus sequence typing (http://www.pasteur.fr/mlst).

The earliest-described strains of hvKP, which were isolated from liver abscesses, were predominantly serotype K1 and ST23 (2). The most frequently isolated non-K1 hvKP stains are currently serotype K2, known to cause hepatic abscesses and severe cases of pneumonia and other hvKP-associated infections such as necrotizing fasciitis (2). The K2 strains isolated to date appear to originate from a much broader range of ST groups that include ST86 and many others (e.g., ST65, ST66, ST373, ST374, ST375, ST380, and ST434) (8,9).

This patient, despite being immunocompromised, was only colonized with what is normally considered a highly pathogenic strain. In general, the acquisition of antimicrobial resistance genes reduces fitness, which could have been the case in this patient. However, other strains carrying MDR and high-virulence genes, namely E. coli ST131, have no loss in fitness (10). These clones might harbor other biologic factors providing a competitive advantage.

MDR strains of K. pneumoniae have emerged in recent years and have been identified as a major threat to public health by the US Centers for Disease Control and Prevention. hvKP, with its high pathogenic potential, has also been on the rise during the same period. In the past, MDR and hvKP strains evolved separately in distinct clonal groups (2), but the recent emergence of hvKP harboring the gene for MDR, such as the one identified in our study, raises newfound concerns. Our patient was colonized with an ST86 CTX-M-3-producing strain of K2 hvKP, raising the question of whether MDR hvKP strains could circulate in Europe.

L.S. received funding from the Fondation pour la Recherche Medicale (grant no. DEA20140630021). A.B. received funding for postdoctoral research from SIDACTION.

References

(1.) Decre D, Verdet C, Emirian A, Le Gourrierec T, Petit JC, Offenstadt G, et al. Emerging severe and fatal infections due to Klebsiella pneumoniae in two university hospitals in France. J Clin Microbiol. 2011; 49:3012-4. http://dx.doi.org/10.1128/JCM.00676-11

(2.) Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy-Vieillard AS, et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis. 2014; 20:1812-20. http://dx.doi.org/10.3201/ eid2011.140206

(3.) McCabe R, Lambert L, Frazee B. Invasive Klebsiella pneumoniae infections, California, USA. Emerg Infect Dis. 2010; 16:1490-1. http://dx.doi.org/10.3201/eid1609.100386

(4.) Zhang R, Lin D, Chan EW, Gu D, Chen GX, Chen S. Emergence of carbapenem-resistant serotype K1 hypervirulent Klebsiella pneumoniae strains in China. Antimicrob Agents Chemother. 2015; 60:709-11. http://dx.doi.org/10.1128/AAC.02173-15

(5.) Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. J Antimicrob Chemother. 2010; 65:490-5. http://dx.doi.org/10.1093/jac/dkp498

(6.) Compain F, Poisson A, Le Hello S, Branger C, Weill FX, Arlet G, et al. Targeting relaxase genes for classification of the predominant plasmids in Enterobacteriaceae. Int J Med Microbiol. 2014; 304:236-42. http://dx.doi.org/10.1016/j.ijmm.2013.09.009

(7.) Compain F, Babosan A, Brisse S, Genel N, Audo J, Ailloud F, et al. Multiplex PCR for detection of seven virulence factors and K1/K2 capsular serotypes of Klebsiella pneumoniae. J Clin Microbiol. 2014; 52:4377-80. http://dx.doi.org/10.1128/JCM.02316-14

(8.) Lin JC, Koh TH, Lee N, Fung CP, Chang FY, Tsai YK, et al. Genotypes and virulence in serotype K2 Klebsiella pneumoniae from liver abscess and non-infectious carriers in Hong Kong, Singapore and Taiwan. Gut Pathog. 2014; 6:21. http://dx.doi.org/10.1186/1757-4749-6-21

(9.) Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS, Engelthaler DM, et al. Mapping the evolution of hypervirulent Klebsiella pneumoniae. MBio. 2015; 6:e00630. http://dx.doi.org/10.1128/mBio.00630-15

(10.) Schaufler K, Semmler T, Pickard DJ, de Toro M, de la Cruz F, Wieler LH, et al. Carriage of extended-spectrum beta-lactamaseplasmids does not reduce fitness but enhances virulence in some strains of pandemic E. coli lineages. Front Microbiol. 2016; 7:336. http://dx.doi.org/10.3389/fmicb.2016.00336

Laure Surgers, Anders Boyd, Pierre-Marie Girard, Guillaume Arlet, Dominique Deere

Author affiliations: Assistance Publique Hopitaux de Paris, Hopital Saint-Antoine, Paris, France (L. Surgers, P-M. Girard, G. Arlet,

D. Deere); Universite Pierre et Marie Curie, Sorbonne Universites, Paris (L. Surgers, A. Boyd, P-M. Girard, G. Arlet, D. Deere)

DOI: http://dx.doi.org/10.3201/eid2209.160681

Address for correspondence: Laure Surgers, Service de Maladies Infectieuses et Tropicales, Hopital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France; email: laure.surgers@aphp.fr
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Author:Surgers, Laure; Boyd, Anders; Girard, Pierre-Marie; Arlet, Guillaume; Decre, Dominique
Publication:Emerging Infectious Diseases
Article Type:Letter to the editor
Date:Sep 1, 2016
Words:1248
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