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Molecular epidemiology of NDM-1- and OXA-48-producing Klebsiella pneumoniae in an Iranian hospital: clonal dissemination of ST11 and ST893

Molecular epidemiology of NDM-1- and OXA-48-producing Klebsiella pneumoniae in an Iranian... Abstract Objectives Despite the fact that the blaOXA-48 and blaNDM-1 genes have successfully disseminated among Klebsiella pneumoniae isolates worldwide, outbreaks remain unidentified in Iran. Here we examined the molecular epidemiology of 96 carbapenem-resistant K. pneumoniae recovered from an Iranian hospital. Methods A total of 96 non-replicate carbapenem-resistant K. pneumoniae were recovered from clinical specimens in a university hospital. Detection of ESBLs and carbapenemases produced by studied strains was performed using PCR and DNA sequencing. The bacterial isolates were assigned to clonal lineages by PFGE and MLST. In addition, plasmids were analysed by PCR-based replicon typing and conjugation assays. Results All isolates harboured blaOXA-48 and blaNDM-1 genes together or alone. Almost all strains also carried ESBL genes. Eighty-seven isolates of K. pneumoniae were categorized into seven pulsotypes. The predominant strain clusters/pulsotypes associated with the outbreak corresponded to ST11 (48/96) and ST893 (31/96). Plasmids carrying blaOXA-48 and blaNDM-1 were successfully transferred to Escherichia coli K12 as the recipient strain. blaOXA-48 was located on IncL/M plasmids of ∼39 kb, while blaNDM-1 was carried by either an IncFII plasmid of ∼50 kb or an untypeable plasmid of ∼4 or 10 kb. Conclusions We describe two separate outbreaks of blaOXA-48- and blaNDM-1-carrying K. pneumoniae strains associated with dissemination of the ST11 and ST893 clones, with the ICU acting as the epicentre. The spread of plasmids carrying carbapenemase genes resulting in fulminant antimicrobial resistance is a severe concern. Introduction Carbapenemase-producing Klebsiella pneumoniae (CPKP) are increasingly reported worldwide and represent a major clinical concern.1,2 Infections due to CPKP are associated with high rates of morbidity and mortality as a result of limited therapeutic options.3,4 The most clinically important carbapenemase genes in CPKP are Ambler class A (KPC type), class B (NDM, VIM and IMP types) and class D (OXA-48-like).5 The blaNDM-1 gene has been detected on different transferable plasmids (IncA/C, IncFII, IncN or untypeable plasmids).6 The blaOXA-48 gene was also carried by various plasmid types, including IncL/M, IncN, IncA/C or untypeable.3 The most important reservoir of NDM-1-producing bacteria is the Indian subcontinent and the Balkan region,7 while Turkey and the wider Mediterranean basin can be considered the main reservoirs of OXA-48-like producers.4,8–10 NDM-1- and OXA-48-producing K. pneumoniae have shown a remarkable ability to spread and in some settings have established high-level endemicity. Hospital outbreaks by NDM-1- or OXA-48-producing K. pneumoniae have been described in Turkey11 and, more recently, in the UK,12 Spain,13 China3 and the Netherlands.14 Iran is located in the Middle East with many of the neighbouring countries having an endemic situation with regards to OXA-48 and NDM-1. The population exchange between countries such as Turkey, Iraq, Pakistan and Afghanistan is high. On one side, there is population transfer from Pakistan and Afghanistan to Iran and on the other side, pilgrimage and tourism of Iranians to Iraq and Turkey. The first report of CPKP in Iran was an imipenem-resistant strain isolated from the urine culture of a 52-year-old male resident in Tehran province in 2011.15 More recently, in 2014, six NDM-1-producing K. pneumoniae were isolated from inpatients at a hospital in Isfahan, Iran.16 However, there is hitherto no information about the STs of CPKP that have circulated in Iran. The aim of this study was to investigate the prevalence of carbapenemase and ESBL resistance determinants in CPKP from Iran, analyse the clonal relatedness of patient isolates and, finally, to characterize plasmids carried in such strains. Materials and methods Bacterial isolates From September 2014 to January 2016, a total of 96 non-duplicate clinical isolates of carbapenem-resistant K. pneumoniae were collected from an 800-bed university hospital in Isfahan, Iran. Isolates were identified by standard biochemical tests and use of API 20E (bioMérieux, Marcy-l’Étoile, France). No ethical approval was obtained for using the clinical samples since they were collected during routine bacteriological analyses in our hospital. Antimicrobial susceptibility testing and phenotypic assays Antimicrobial susceptibility testing was performed using the disc diffusion method. The MICs of imipenem, meropenem and ertapenem antibiotics (Liofilchem, Italy) were determined by gradient test strips based on CLSI guidelines.17 The MIC of colistin was determined by Etest strips (bioMérieux). EUCAST breakpoints were used for interpretation.18,Escherichia coli ATCC 25922 was used as the quality control strain for antimicrobial susceptibility testing. Following CLSI recommendations, the modified Hodge test (MHT) was used as a phenotypic method to detect carbapenemase-producing strains with ertapenem discs.17 Molecular detection of genes encoding carbapenemases and ESBLs Plasmid DNA was extracted using the GeneAll Exprep Plasmid kit (GeneAll Biotechnology, Seoul, Korea). PCR assays were carried out for detection of blaKPC, blaGES, blaVIM, blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaTEM and blaSHV genes using a set of specific primers as previously described.15,19 The primers used for the detection of SHV β-lactamase amplify solely the ESBL genes and not the chromosomally encoded SHV-1. The DNA amplicons were sequenced using an ABI Capillary System (Macrogen Research, Seoul, Korea). Molecular typing methods The clonal relatedness among the 96 CPKP isolates was characterized by the PFGE method. Genomic DNAs were digested with XbaI restriction endonuclease (Fermentas) and DNA bands electroporated using a CHEF-DRIII system (Bio-Rad Laboratories), with a linear pulse time ramped from 5 to 30 s for 20 h at 14°C and constant voltage of 6 V/cm. Isolates that exhibited similarity cut-off ≥80% were considered a pulsotype.20 MLST was performed according to the protocol described on the K. pneumoniae MLST website (http://www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html). Plasmid analysis and conjugation experiments Experiments focused on the potential for conjugational transfer of carbapenem resistance. Filter mating assays were carried out, with E. coli K12 [F−lac+ Nal (r)] as the recipient strain. Isolates ES39, ES49 and E69, which harboured only the blaNDM-1 or blaOXA-48 gene, and isolates ES94 and ES132, which harboured the blaOXA-48 and blaNDM-1 genes, were selected and used. Transconjugants were selected on MacConkey agar plates containing 32 mg/L nalidixic acid and 1 mg/L meropenem.21 The blaNDM-1 and blaOXA-48 genes were identified by PCR amplification. Plasmid DNA was isolated from both donor and transconjugant strains using the GeneAll Exprep Plasmid kit. The plasmid bands were observed on 0.7% agarose gels. The extracted plasmids of these isolates were digested by HindIII restriction enzyme (Fermentas) and restriction patterns were compared. Plasmid incompatibility was determined by a PCR-based replicon typing scheme, as previously described.22 GenBank accession numbers The nucleotide sequences of the blaNDM-1 and blaOXA-48 genes were assigned GenBank accession numbers KX467530 and KX246861, respectively. Results Bacterial isolates From September 2014 to January 2016, a total of 96 isolates of carbapenem-resistant K. pneumoniae were collected from 96 patients. Seventy-four isolates (77%) were isolated from ICU wards, whereas the remaining isolates were recovered from other wards. The isolates were predominantly collected from tracheal secretions (49/96; 51.0%) and urine (24/96; 25%). Other sites of isolation included wound secretions (6/96; 6.2%), blood (4/96; 4.2%), catheter (4/96; 4.2%), CSF (4/96; 4.2%), sputum (1/96; 1%), nasal cavity (1/96; 1%), bronchoalveolar lavage (BAL) (1/96; 1%), throat (1/96; 1%) and pleural fluid (1/96; 1%) (Figure 1). Figure 1. View largeDownload slide Dendrogram based on PFGE of 96 isolates of CPKP and their STs determined via MLST. M, male; F, female. Figure 1. View largeDownload slide Dendrogram based on PFGE of 96 isolates of CPKP and their STs determined via MLST. M, male; F, female. Antimicrobial susceptibility testing Overall, all of the isolates were resistant to at least three classes of antibiotic and they were considered MDR. The rates of resistance to imipenem, meropenem and ertapenem among isolates were 87.5% (84/96), 95.8% (92/96) and 100% (96/96), respectively. All isolates were resistant to ertapenem, with MICs ranging from 4 to 8 mg/L. The isolates exhibited various levels of resistance to imipenem and meropenem. The rate of isolates exhibiting resistance to colistin was 9.4% (9/96), with MICs ranging from 6 to 64 mg/L. It should be noted that the gradient test method can both underestimate and overestimate colistin resistance. The MICs of carbapenem agents for all isolates are shown in Table 1. The percentages of resistance to other antimicrobial agents were as follows: amikacin 52.1% (50/96); gentamicin 84.4% (81/96); aztreonam 97.9% (94/96); ciprofloxacin 97.9% (94/96); and fosfomycin 10.4% (10/96). All K. pneumoniae isolates demonstrated resistance to ceftazidime, cefotaxime and cefepime whereas all of them were susceptible to tigecycline. Table 1. Phenotypic and genotypic characteristics of 96 CPKP isolates Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND S, susceptible; IPM, imipenem; MEM, meropenem; ETP, ertapenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable; ND, not determined. Table 1. Phenotypic and genotypic characteristics of 96 CPKP isolates Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND S, susceptible; IPM, imipenem; MEM, meropenem; ETP, ertapenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable; ND, not determined. Seventy-seven of the 96 isolates (80.2%) were phenotypically carbapenemase positive in terms of the ertapenem-MHT method. Carbapenemase and ESBL genes Overall, 56 out of the 96 CPKP (58.3%) harboured only the blaOXA-48 gene and 6 (6.3%) carried only the blaNDM-1 gene. Thirty-four (35.4%) of these isolates co-produced the blaNDM-1 and blaOXA-48 genes (Table 1). Other carbapenemases genes, including blaKPC, blaVIM and blaIMP, were not detected among isolates. The genotyping results of the ESBL-producing isolates obtained by PCR amplification of CTX-M, TEM and SHV genes are shown in Table 1. Among the 96 isolates, 94 (97.9%) ESBL producers were observed. Of the 94 ESBL producers, only ES138 harboured solely the CTX-M-15 gene and only ES122 and ES133 the SHV ESBL gene, whereas 93.6% (88/94) of isolates included all three genes together. In addition, 3.2% (3/94) of isolates (ES131, ES132 and ES134) included the CTX-M-15 and SHV genes together. Clonal relatedness of CPKP isolates PFGE revealed that 87 of the 96 CPKP could be categorized into seven pulsotypes: A (47 isolates), B (29 isolates), C (2 isolates), D (3 isolates), E (2 isolates), F (2 isolates) and G (2 isolates), whereas 9 isolates appeared to be singletons (Figure 1). MLST demonstrated that each of the K. pneumoniae PFGE pulsotypes was associated with a unique ST. Strains belonging to pulsotypes A, B, C, E, F and G were assigned to ST11, ST893, ST893, ST147, ST147 and ST915, respectively. ST11 and ST893 were two major STs (Figure 1), comprising 48 and 31 isolates, respectively. Plasmid replicon typing and conjugation assays Plasmid replicon typing revealed that 47 blaOXA-48-carrying and 10 blaNDM-1-carrying K. pneumoniae isolates contained plasmid types belonging to IncL/M and IncFII, respectively. In just one isolate of ST11 (ES77), the blaOXA-48 gene was found to be associated with an IncT plasmid. In the other 32 isolates we could not identify the incompatibility group (6 isolates not determined). Conjugation assays showed that the plasmids carrying blaOXA-48 and blaNDM-1 genes in all five strains were successfully transferred to E. coli K12 as the recipient strain. The antimicrobial resistance profile of the transconjugants is shown in Table 2. PCR confirmed the presence of the blaOXA-48 and blaNDM-1 genes in the transconjugants; all transconjugants, except Tc-ES49, also harboured blaCTX-M-15 and blaTEM genes. Table 2. Microbiological characteristics of five clinical CPKP isolates and their transconjugants Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ETP, ertapenem; MEM, meropenem; IPM, imipenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable. a Tc, E. coli K12 transconjugant selected in medium containing 1 mg/L meropenem. Table 2. Microbiological characteristics of five clinical CPKP isolates and their transconjugants Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ETP, ertapenem; MEM, meropenem; IPM, imipenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable. a Tc, E. coli K12 transconjugant selected in medium containing 1 mg/L meropenem. Plasmid analysis indicated that blaOXA-48 in transconjugants Tc-ES39 and Tc-ES69 was located on ∼39 kb IncL/M conjugative plasmids (Table 2); the two plasmids showed identical profiles after HindIII digestion (data not shown). In Tc-ES49, blaNDM-1 was found on a ∼50 kb IncFII conjugative plasmid. Transconjugants Tc-ES132 and Tc-ES94 each contained a single plasmid; the two plasmids had distinct restriction profiles (data not shown). Transconjugants Tc-ES132 and Tc-ES94 were only positive for blaOXA-48, blaCTX-M-15 and blaTEM genes, whereas they were negative for the blaNDM-1 gene. In initial isolates of ES94 and ES132, plasmid gel extraction followed by PCR amplification revealed that the blaOXA-48 gene was harboured on a transferable plasmid of ∼39 kb belonging to the IncL/M incompatibility group, whereas the blaNDM-1 gene was carried on a non-conjugative plasmid of ∼4 or 10 kb. Discussion This study highlights the finding of CPKP with blaOXA-48 and blaNDM-1 genes together or alone, in a hospital in Isfahan. The co-occurrence of OXA-48- and NDM-1-producing K. pneumoniae has been reported in some Asian and European countries.1,3,23,24 In this hospital, blaNDM-1 was first isolated in March 201316 and the prevalence of blaNDM-1-producing K. pneumoniae isolates collected at this hospital increased from 12.2% in 2013–14 to 41.7% in 2015–16 (our study). In addition, our previous study in this hospital showed that intestinal carriage rates of NDM-1- and OXA-48-producing Enterobacteriaceae are high, suggesting that NDM-1 and OXA-48 have become endemic.25 In addition to recent observations in neighbouring countries (Kuwait26 and Lebanon9), this indicates the emergence of this resistance mechanism in the Middle East. Analysis of transconjugants revealed that the blaOXA-48 gene, together with blaCTX-M-15 and blaTEM, were carried on ∼39 kb transferable plasmids belonging to the IncL/M incompatibility group, in accordance with other studies showing that blaOXA-48 was carried by an epidemic plasmid worldwide.1,3 Previous studies have reported that the spread of blaNDM-1 is linked to different types of IncA/C, IncF, IncN and untypeable plasmids.6,27 We found Tc-ES49 carrying blaNDM-1 in a ∼50 kb IncFII plasmid (Table 2). Transferable IncL/M and IncFII plasmids have greatly contributed to the dissemination of antibiotic resistance genes such as blaOXA-48, blaNDM-1 and blaCTX-M-15 among K. pneumoniae, but they also have the ability to transfer between other enterobacterial species.6,28,29 In the present study, pulsotype A (n = 47) and pulsotype B (n = 29) corresponded to ST11 and ST893, respectively (Figure 1). ST11 and ST893 have been circulating in this hospital setting during the period of investigation, indicating two separate outbreaks, with the ICU acting as the epicentre. Interestingly, two clones were overlapping and most isolates were identified in February 2015. Hospital outbreaks linked to CPKP have been previously reported and are likely associated with particular clonal lineages, similar to our study.3,29 Therefore, it is crucial to identify the clonal relatedness among the CPKP to strengthen the surveillance and reporting system in hospital infection control measures. ST11 (47 pulsotype A and 1 singleton) was the predominant CPKP that disseminated across 10 wards. All ST11 isolates carried the blaOXA-48 gene, whereas six isolates of ST11 co-produced blaOXA-48 and blaNDM-1 genes. ST11 is a single-locus variant of the pandemic ST258 clone and it was considered a high-risk epidemic clone owing to its ability to spread rapidly and disseminate β-lactamases (such as ESBLs and carbapenemases). In the present study, the majority of ST11 isolates carried OXA-48 and CTX-M-15 genes. Previous studies have also identified a high frequency of association between CTX-M-15 and OXA-48 or NDM-1 in ST11 isolates.1,3,6 ST893 (29 pulsotype B and 2 pulsotype C) was the second most common ST in our study and was isolated from patients in six different wards. Overall, co-existence of blaOXA-48 and blaNDM-1 genes among this clone was found to be 77.4% (24/31). The co-production of these two genes in ST893 accounted for its high resistance to carbapenems (Table 1). ST893 has only been reported in China and has not been associated with ESBLs or carbapenemases.30 In our study, five minor pulsotypes were also observed (C, D, E, F and G). Pulsotype C included the two ST893 isolates. ST147 (pulsotypes E and F) that harboured an IncFII plasmid and was positive for blaNDM-1 and ESBL genes was isolated from four patients on three different wards. Also, two NDM-1-positive ST147 isolates produced OXA-48. The ST147 isolates have been identified in OXA-48 and OXA-204 producers in France31,32 and China3 and also reported in NDM-1 producers in Tunisia33 and Oman.34 ST915 (pulsotype G) carried the blaNDM-1 gene, which was isolated from two patients on two different wards. The most remarkable finding from our study is that the ST893 and ST915 clones have not been previously linked with NDM and OXA-48 production and are not clustered with any of the high-risk clones previously associated with these enzymes, which could indicate that the spread of carbapenemases is evolving towards new STs. In conclusion, a clonal dissemination and outbreak of OXA-48- and NDM-1-producing K. pneumoniae that co-produce ESBLs has been observed. ST11 and ST893 K. pneumoniae were the predominant clones that were associated with the two separate outbreaks and harboured a host narrow-range IncFII plasmid of ∼50 kb or broad-range IncL/M plasmid of ∼39 kb. There is no doubt the emergence and spread of NDM-1 and OXA-48 in K. pneumoniae will further limit clinical therapeutic options and threaten the public health of Iran. It is crucial that strict infection control measures should be adopted to control CPKP outbreaks in our clinical settings. Acknowledgements We would like to thank the personnel of the Bacteriology Department of the Pasteur Institute of Iran for their assistance and Muhammad Humaun Kabir for excellent technical assistance. Funding This work was funded by research grants from the Pasteur Institute of Iran (project no. IR.PII.REC.1395.51). Transparency declarations None to declare. References 1 Brãnas P , Villa J , Viedma E et al. Molecular epidemiology of carbapenemase-producing Klebsiella pneumoniae in a hospital in Madrid: successful establishment of an OXA-48 ST11 clone . Int J Antimicrob Agents 2015 ; 46 : 111 – 6 . Google Scholar CrossRef Search ADS PubMed 2 Qi Y , Wei Z , Ji S et al. ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China . J Antimicrob Chemother 2011 ; 66 : 307 – 12 . Google Scholar CrossRef Search ADS PubMed 3 Guo L , An J , Ma Y et al. Nosocomial outbreak of OXA-48-producing Klebsiella pneumoniae in a Chinese hospital: clonal transmission of ST147 and ST383 . PLoS One 2016 ; 11 : e0160754 . Google Scholar CrossRef Search ADS PubMed 4 Lascols C , Peirano G , Hackel M et al. Surveillance and molecular epidemiology of Klebsiella pneumoniae isolates that produce carbapenemases: first report of OXA-48-like enzymes in North America . Antimicrob Agents Chemother 2013 ; 57 : 130 – 6 . Google Scholar CrossRef Search ADS PubMed 5 Hrabak J , Chudackova E , Papagiannitsis CC. Detection of carbapenemases in Enterobacteriaceae: a challenge for diagnostic microbiological laboratories . Clin Microbiol Infect 2014 ; 20 : 839 – 53 . Google Scholar CrossRef Search ADS PubMed 6 Voulgari E , Gartzonika C , Vrioni G et al. The Balkan region: NDM-1-producing Klebsiella pneumoniae ST11 clonal strain causing outbreaks in Greece . J Antimicrob Chemother 2014 ; 69 : 2091 – 7 . Google Scholar CrossRef Search ADS PubMed 7 Dortet L , Poirel L , Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria . Biomed Res Int 2014 ; 2014 : 249856. Google Scholar CrossRef Search ADS PubMed 8 Kilic A , Baysallar A. The first Klebsiella pneumoniae isolate co-producing OXA-48 and NDM-1 in Turkey . Ann Lab Med 2015 ; 35 : 382 – 3 . Google Scholar CrossRef Search ADS PubMed 9 Dandachi I , Salem Sokhn E , Najem E et al. Carriage of β-lactamase-producing Enterobacteriaceae among nursing home residents in north Lebanon . Int J Infect Dis 2016 ; 45 : 24 – 31 . Google Scholar CrossRef Search ADS PubMed 10 Mairi A , Pantel A , Sotto A et al. OXA-48-like carbapenemases producing Enterobacteriaceae in different niches . Eur J Clin Microbiol Infect Dis 2017 ; doi:10.1007/s10096-017-3112-7. 11 Carrër A , Poirel L , Eraksoy H et al. Spread of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in Istanbul, Turkey . Antimicrob Agents Chemother 2008 ; 52 : 2950 – 4 . Google Scholar CrossRef Search ADS PubMed 12 Thomas CP , Moore LS , Elamin N et al. Early (2008-2010) hospital outbreak of Klebsiella pneumoniae producing OXA-48 carbapenemase in the UK . Int J Antimicrob Agents 2013 ; 42 : 531 – 6 . Google Scholar CrossRef Search ADS PubMed 13 Pitart C , Solé M , Roca I et al. First outbreak of a plasmid-mediated carbapenem-hydrolyzing OXA-48 β-lactamase in Klebsiella pneumoniae in Spain . Antimicrob Agents Chemother 2011 ; 55 : 4398 – 401 . Google Scholar CrossRef Search ADS PubMed 14 Bosch T , Lutgens SPM , Hermans MHA et al. An outbreak of NDM-1 producing Klebsiella pneumoniae in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in unrelated healthcare centers . J Clin Microbiol 2017 ; 55 : 2380 – 90 . Google Scholar CrossRef Search ADS PubMed 15 Shahcheraghi F , Nobari S , Rahmati Ghezelgeh F et al. First report of New Delhi metallo-β-lactamase-1-producing Klebsiella pneumoniae in Iran . Microb Drug Resist 2013 ; 19 : 30 – 6 . Google Scholar CrossRef Search ADS PubMed 16 Fazeli H , Norouzi-Barough M , Ahadi AM et al. Detection of New Delhi metallo-β-lactamase-1 (NDM-1) in carbapenem-resistant Klebsiella pneumoniae isolated from a university hospital in Iran . Hippokratia 2015 ; 19 : 205 – 9 . Google Scholar PubMed 17 Clinical and Laboratory Standards Institute . Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Fifth Informational Supplement M100-S26 . CLSI , Wayne, PA, USA , 2016 . 18 EUCAST . Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 6.0, 2016 . http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_6.0_Breakpoint_table.pdf. 19 Poirel L , Walsh TR , Cuvillier V et al. Multiplex PCR for detection of acquired carbapenemase genes . Diagn Microbiol Infect Dis 2011 ; 70 : 119 – 23 . Google Scholar CrossRef Search ADS PubMed 20 Tenover FC , Arbeit RD , Goering RV et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing . J Clin Microbiol 1995 ; 33 : 2233 – 9 . Google Scholar PubMed 21 Lyimo B , Buza J , Subbiah M et al. IncF plasmids are commonly carried by antibiotic resistant Escherichia coli isolated from drinking water sources in northern Tanzania . Int J Microbiol 2016 ; 2016 : 3103672 . Google Scholar CrossRef Search ADS PubMed 22 Carattoli A , Bertini A , Villa L et al. Identification of plasmids by PCR-based replicon typing . J Microbiol Methods 2005 ; 63 : 219 – 28 . Google Scholar CrossRef Search ADS PubMed 23 Lixandru BE , Cotar AL , Strau M et al. Carbapenemase-producing Klebsiella pneumoniae in Romania: a six-month survey . PLoS One 2015 ; 10 : e0143214 . Google Scholar CrossRef Search ADS PubMed 24 Jamal WY , Albert MJ , Khodakhast F et al. Emergence of new sequence type OXA-48 carbapenemase-producing Enterobacteriaceae in Kuwait . Microb Drug Resist 2015 ; 21 : 329 – 34 . Google Scholar CrossRef Search ADS PubMed 25 Solgi H , Badmasti F , Aminzadeh Z et al. Molecular characterization of intestinal carriage of carbapenem-resistant Enterobacteriaceae among inpatients at two Iranian university hospitals: first report of co-production of blaNDM-7 and blaOXA-48 . Eur J Clin Microbiol Infect Dis 2017 ; 36 : 2127 – 35 . Google Scholar CrossRef Search ADS PubMed 26 Jamal WY , Albert MJ , Rotimi VO. High prevalence of New Delhi metallo-β-lactamase-1 (NDM-1) producers among carbapenem-resistant Enterobacteriaceae in Kuwait . PLoS One 2016 ; 11 : e0152638. Google Scholar CrossRef Search ADS PubMed 27 Giske CG , Fröding I , Hasan CM et al. Diverse sequence types of Klebsiella pneumoniae contribute to the dissemination of blaNDM-1 in India, Sweden, and the United Kingdom . Antimicrob Agents Chemother 2012 ; 56 : 2735 – 8 . Google Scholar CrossRef Search ADS PubMed 28 Qu H , Wang X , Ni Y et al. NDM-1-producing Enterobacteriaceae in a teaching hospital in Shanghai, China: incX3-type plasmids may contribute to the dissemination of blaNDM-1 . Int J Infect Dis 2015 ; 34 : 8 – 13 . Google Scholar CrossRef Search ADS PubMed 29 Torres-González P , Bobadilla-Del Valle M , Tovar-Calderón E et al. Outbreak caused by Enterobacteriaceae harboring NDM-1 metallo-β-lactamase carried in an IncFII plasmid in a tertiary care hospital in Mexico City . Antimicrob Agents Chemother 2015 ; 59 : 7080 – 3 . Google Scholar CrossRef Search ADS PubMed 30 Wang Q , Li B , Tsang AK et al. Genotypic analysis of Klebsiella pneumoniae isolates in a Beijing hospital reveals high genetic diversity and clonal population structure of drug-resistant isolates . PLoS One 2013 ; 8 : e57091 . Google Scholar CrossRef Search ADS PubMed 31 Liapis E , Pantel A , Robert J et al. Molecular epidemiology of OXA-48-producing Klebsiella pneumoniae in France . Clin Microbiol Infect 2014 ; 20 : 1121 – 3 . Google Scholar CrossRef Search ADS 32 Potron A , Bernabeu S , Cuzon G et al. Analysis of OXA-204 carbapenemase-producing Enterobacteriaceae reveals possible endoscopy-associated transmission, France, 2012 to 2014 . Euro Surveill 2017 ; 22 : pii=17-00048. 33 Messaoudi A , Haenni M , Mansour W et al. ST147 NDM-1-producing Klebsiella pneumoniae spread in two Tunisian hospitals . J Antimicrob Chemother 2017 ; 72 : 315 – 6 . Google Scholar CrossRef Search ADS PubMed 34 Dortet L , Poirel L , Al Yaqoubi F et al. NDM-1, OXA-48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate of Oman . Clin Microbiol Infect 2012 ; 18 : 144 – 8 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

Molecular epidemiology of NDM-1- and OXA-48-producing Klebsiella pneumoniae in an Iranian hospital: clonal dissemination of ST11 and ST893

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
ISSN
0305-7453
eISSN
1460-2091
DOI
10.1093/jac/dky081
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Abstract

Abstract Objectives Despite the fact that the blaOXA-48 and blaNDM-1 genes have successfully disseminated among Klebsiella pneumoniae isolates worldwide, outbreaks remain unidentified in Iran. Here we examined the molecular epidemiology of 96 carbapenem-resistant K. pneumoniae recovered from an Iranian hospital. Methods A total of 96 non-replicate carbapenem-resistant K. pneumoniae were recovered from clinical specimens in a university hospital. Detection of ESBLs and carbapenemases produced by studied strains was performed using PCR and DNA sequencing. The bacterial isolates were assigned to clonal lineages by PFGE and MLST. In addition, plasmids were analysed by PCR-based replicon typing and conjugation assays. Results All isolates harboured blaOXA-48 and blaNDM-1 genes together or alone. Almost all strains also carried ESBL genes. Eighty-seven isolates of K. pneumoniae were categorized into seven pulsotypes. The predominant strain clusters/pulsotypes associated with the outbreak corresponded to ST11 (48/96) and ST893 (31/96). Plasmids carrying blaOXA-48 and blaNDM-1 were successfully transferred to Escherichia coli K12 as the recipient strain. blaOXA-48 was located on IncL/M plasmids of ∼39 kb, while blaNDM-1 was carried by either an IncFII plasmid of ∼50 kb or an untypeable plasmid of ∼4 or 10 kb. Conclusions We describe two separate outbreaks of blaOXA-48- and blaNDM-1-carrying K. pneumoniae strains associated with dissemination of the ST11 and ST893 clones, with the ICU acting as the epicentre. The spread of plasmids carrying carbapenemase genes resulting in fulminant antimicrobial resistance is a severe concern. Introduction Carbapenemase-producing Klebsiella pneumoniae (CPKP) are increasingly reported worldwide and represent a major clinical concern.1,2 Infections due to CPKP are associated with high rates of morbidity and mortality as a result of limited therapeutic options.3,4 The most clinically important carbapenemase genes in CPKP are Ambler class A (KPC type), class B (NDM, VIM and IMP types) and class D (OXA-48-like).5 The blaNDM-1 gene has been detected on different transferable plasmids (IncA/C, IncFII, IncN or untypeable plasmids).6 The blaOXA-48 gene was also carried by various plasmid types, including IncL/M, IncN, IncA/C or untypeable.3 The most important reservoir of NDM-1-producing bacteria is the Indian subcontinent and the Balkan region,7 while Turkey and the wider Mediterranean basin can be considered the main reservoirs of OXA-48-like producers.4,8–10 NDM-1- and OXA-48-producing K. pneumoniae have shown a remarkable ability to spread and in some settings have established high-level endemicity. Hospital outbreaks by NDM-1- or OXA-48-producing K. pneumoniae have been described in Turkey11 and, more recently, in the UK,12 Spain,13 China3 and the Netherlands.14 Iran is located in the Middle East with many of the neighbouring countries having an endemic situation with regards to OXA-48 and NDM-1. The population exchange between countries such as Turkey, Iraq, Pakistan and Afghanistan is high. On one side, there is population transfer from Pakistan and Afghanistan to Iran and on the other side, pilgrimage and tourism of Iranians to Iraq and Turkey. The first report of CPKP in Iran was an imipenem-resistant strain isolated from the urine culture of a 52-year-old male resident in Tehran province in 2011.15 More recently, in 2014, six NDM-1-producing K. pneumoniae were isolated from inpatients at a hospital in Isfahan, Iran.16 However, there is hitherto no information about the STs of CPKP that have circulated in Iran. The aim of this study was to investigate the prevalence of carbapenemase and ESBL resistance determinants in CPKP from Iran, analyse the clonal relatedness of patient isolates and, finally, to characterize plasmids carried in such strains. Materials and methods Bacterial isolates From September 2014 to January 2016, a total of 96 non-duplicate clinical isolates of carbapenem-resistant K. pneumoniae were collected from an 800-bed university hospital in Isfahan, Iran. Isolates were identified by standard biochemical tests and use of API 20E (bioMérieux, Marcy-l’Étoile, France). No ethical approval was obtained for using the clinical samples since they were collected during routine bacteriological analyses in our hospital. Antimicrobial susceptibility testing and phenotypic assays Antimicrobial susceptibility testing was performed using the disc diffusion method. The MICs of imipenem, meropenem and ertapenem antibiotics (Liofilchem, Italy) were determined by gradient test strips based on CLSI guidelines.17 The MIC of colistin was determined by Etest strips (bioMérieux). EUCAST breakpoints were used for interpretation.18,Escherichia coli ATCC 25922 was used as the quality control strain for antimicrobial susceptibility testing. Following CLSI recommendations, the modified Hodge test (MHT) was used as a phenotypic method to detect carbapenemase-producing strains with ertapenem discs.17 Molecular detection of genes encoding carbapenemases and ESBLs Plasmid DNA was extracted using the GeneAll Exprep Plasmid kit (GeneAll Biotechnology, Seoul, Korea). PCR assays were carried out for detection of blaKPC, blaGES, blaVIM, blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaTEM and blaSHV genes using a set of specific primers as previously described.15,19 The primers used for the detection of SHV β-lactamase amplify solely the ESBL genes and not the chromosomally encoded SHV-1. The DNA amplicons were sequenced using an ABI Capillary System (Macrogen Research, Seoul, Korea). Molecular typing methods The clonal relatedness among the 96 CPKP isolates was characterized by the PFGE method. Genomic DNAs were digested with XbaI restriction endonuclease (Fermentas) and DNA bands electroporated using a CHEF-DRIII system (Bio-Rad Laboratories), with a linear pulse time ramped from 5 to 30 s for 20 h at 14°C and constant voltage of 6 V/cm. Isolates that exhibited similarity cut-off ≥80% were considered a pulsotype.20 MLST was performed according to the protocol described on the K. pneumoniae MLST website (http://www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html). Plasmid analysis and conjugation experiments Experiments focused on the potential for conjugational transfer of carbapenem resistance. Filter mating assays were carried out, with E. coli K12 [F−lac+ Nal (r)] as the recipient strain. Isolates ES39, ES49 and E69, which harboured only the blaNDM-1 or blaOXA-48 gene, and isolates ES94 and ES132, which harboured the blaOXA-48 and blaNDM-1 genes, were selected and used. Transconjugants were selected on MacConkey agar plates containing 32 mg/L nalidixic acid and 1 mg/L meropenem.21 The blaNDM-1 and blaOXA-48 genes were identified by PCR amplification. Plasmid DNA was isolated from both donor and transconjugant strains using the GeneAll Exprep Plasmid kit. The plasmid bands were observed on 0.7% agarose gels. The extracted plasmids of these isolates were digested by HindIII restriction enzyme (Fermentas) and restriction patterns were compared. Plasmid incompatibility was determined by a PCR-based replicon typing scheme, as previously described.22 GenBank accession numbers The nucleotide sequences of the blaNDM-1 and blaOXA-48 genes were assigned GenBank accession numbers KX467530 and KX246861, respectively. Results Bacterial isolates From September 2014 to January 2016, a total of 96 isolates of carbapenem-resistant K. pneumoniae were collected from 96 patients. Seventy-four isolates (77%) were isolated from ICU wards, whereas the remaining isolates were recovered from other wards. The isolates were predominantly collected from tracheal secretions (49/96; 51.0%) and urine (24/96; 25%). Other sites of isolation included wound secretions (6/96; 6.2%), blood (4/96; 4.2%), catheter (4/96; 4.2%), CSF (4/96; 4.2%), sputum (1/96; 1%), nasal cavity (1/96; 1%), bronchoalveolar lavage (BAL) (1/96; 1%), throat (1/96; 1%) and pleural fluid (1/96; 1%) (Figure 1). Figure 1. View largeDownload slide Dendrogram based on PFGE of 96 isolates of CPKP and their STs determined via MLST. M, male; F, female. Figure 1. View largeDownload slide Dendrogram based on PFGE of 96 isolates of CPKP and their STs determined via MLST. M, male; F, female. Antimicrobial susceptibility testing Overall, all of the isolates were resistant to at least three classes of antibiotic and they were considered MDR. The rates of resistance to imipenem, meropenem and ertapenem among isolates were 87.5% (84/96), 95.8% (92/96) and 100% (96/96), respectively. All isolates were resistant to ertapenem, with MICs ranging from 4 to 8 mg/L. The isolates exhibited various levels of resistance to imipenem and meropenem. The rate of isolates exhibiting resistance to colistin was 9.4% (9/96), with MICs ranging from 6 to 64 mg/L. It should be noted that the gradient test method can both underestimate and overestimate colistin resistance. The MICs of carbapenem agents for all isolates are shown in Table 1. The percentages of resistance to other antimicrobial agents were as follows: amikacin 52.1% (50/96); gentamicin 84.4% (81/96); aztreonam 97.9% (94/96); ciprofloxacin 97.9% (94/96); and fosfomycin 10.4% (10/96). All K. pneumoniae isolates demonstrated resistance to ceftazidime, cefotaxime and cefepime whereas all of them were susceptible to tigecycline. Table 1. Phenotypic and genotypic characteristics of 96 CPKP isolates Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND S, susceptible; IPM, imipenem; MEM, meropenem; ETP, ertapenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable; ND, not determined. Table 1. Phenotypic and genotypic characteristics of 96 CPKP isolates Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND Strain MHT MIC (mg/L) Antimicrobial resistance phenotype Carbapenemase gene(s) Associated β-lactamases Inc group IPM MEM ETP ES1 − 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 — UT ES14 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15a + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES15b + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES16a + S 4 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 — IncL/M ES16b − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES17 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES18 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES19 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES20 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES22 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES23 + S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES25 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES26 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES31 − S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES32a + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, FOF, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES32b + 48 8 8 CAZ, CTX, FEP, ATM, CIP, FOF blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES33 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES35 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES36 + S S 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES38 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES39 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES40 + S 4 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES42 + S 2 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES43 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES44 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES46 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES47 − 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES48 + 4 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES49 − S 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES50 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES51 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES54 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES55 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES56 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES57 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES58 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES60 − 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES61 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES62 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES68 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES69 − 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES70 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES72 + 24 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES73 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES74 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES75 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES76 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES77 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncT ES78 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES79 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES80 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES81 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES82 – 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES83 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES84 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES86 + 16 6 6 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES87 + 4 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES88 + 256 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES89 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES91 + S 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES92 + 48 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES94 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES97 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES98 + 34 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES99 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES100 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES101 + 48 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES102 + 24 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES103 − 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV ND ES105 + 256 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES107 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES108 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES109 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV ND ES110 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES111 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncL/M ES112 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES113 + 8 8 8 CAZ, CTX, FEP, ATM, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES115 + S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES116 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES117 + 16 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES118 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES119 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES120 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES121 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaTEM, blaSHV UT ES122 + 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP blaOXA-48, blaNDM-1 blaSHV IncL/M ES124 + 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaTEM, blaSHV IncFII ES125 + 16 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES130 + 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES131 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF blaOXA-48 blaCTX-M-15, blaSHV IncL/M ES132 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP blaOXA-48, blaNDM-1 blaCTX-M-15, blaSHV UT ES133 − 8 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaSHV UT ES134 − 8 8 8 CAZ, CTX, FEP blaNDM-1 blaCTX-M-15, blaSHV IncFII ES135 + 16 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV UT ES137 + 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF, CST blaOXA-48 blaCTX-M-15, blaTEM, blaSHV IncL/M ES138 − S 8 8 CAZ, CTX, FEP, ATM, CIP blaOXA-48 blaCTX-M-15 ND S, susceptible; IPM, imipenem; MEM, meropenem; ETP, ertapenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable; ND, not determined. Seventy-seven of the 96 isolates (80.2%) were phenotypically carbapenemase positive in terms of the ertapenem-MHT method. Carbapenemase and ESBL genes Overall, 56 out of the 96 CPKP (58.3%) harboured only the blaOXA-48 gene and 6 (6.3%) carried only the blaNDM-1 gene. Thirty-four (35.4%) of these isolates co-produced the blaNDM-1 and blaOXA-48 genes (Table 1). Other carbapenemases genes, including blaKPC, blaVIM and blaIMP, were not detected among isolates. The genotyping results of the ESBL-producing isolates obtained by PCR amplification of CTX-M, TEM and SHV genes are shown in Table 1. Among the 96 isolates, 94 (97.9%) ESBL producers were observed. Of the 94 ESBL producers, only ES138 harboured solely the CTX-M-15 gene and only ES122 and ES133 the SHV ESBL gene, whereas 93.6% (88/94) of isolates included all three genes together. In addition, 3.2% (3/94) of isolates (ES131, ES132 and ES134) included the CTX-M-15 and SHV genes together. Clonal relatedness of CPKP isolates PFGE revealed that 87 of the 96 CPKP could be categorized into seven pulsotypes: A (47 isolates), B (29 isolates), C (2 isolates), D (3 isolates), E (2 isolates), F (2 isolates) and G (2 isolates), whereas 9 isolates appeared to be singletons (Figure 1). MLST demonstrated that each of the K. pneumoniae PFGE pulsotypes was associated with a unique ST. Strains belonging to pulsotypes A, B, C, E, F and G were assigned to ST11, ST893, ST893, ST147, ST147 and ST915, respectively. ST11 and ST893 were two major STs (Figure 1), comprising 48 and 31 isolates, respectively. Plasmid replicon typing and conjugation assays Plasmid replicon typing revealed that 47 blaOXA-48-carrying and 10 blaNDM-1-carrying K. pneumoniae isolates contained plasmid types belonging to IncL/M and IncFII, respectively. In just one isolate of ST11 (ES77), the blaOXA-48 gene was found to be associated with an IncT plasmid. In the other 32 isolates we could not identify the incompatibility group (6 isolates not determined). Conjugation assays showed that the plasmids carrying blaOXA-48 and blaNDM-1 genes in all five strains were successfully transferred to E. coli K12 as the recipient strain. The antimicrobial resistance profile of the transconjugants is shown in Table 2. PCR confirmed the presence of the blaOXA-48 and blaNDM-1 genes in the transconjugants; all transconjugants, except Tc-ES49, also harboured blaCTX-M-15 and blaTEM genes. Table 2. Microbiological characteristics of five clinical CPKP isolates and their transconjugants Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ETP, ertapenem; MEM, meropenem; IPM, imipenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable. a Tc, E. coli K12 transconjugant selected in medium containing 1 mg/L meropenem. Table 2. Microbiological characteristics of five clinical CPKP isolates and their transconjugants Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M Isolate ST MIC (mg/L) Antimicrobial resistance phenotype β-Lactamase(s) Size of plasmids (kb) Inc group ETP MEM IPM ES39 11 8 8 48 CAZ, CTX, FEP, ATM, AMK, GEN, CIP, FOF OXA-48, CTX-M-15, TEM, SHV ∼39 IncL/M Tc-ES39a — 2 1 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES49 11 8 8 S CAZ, CTX, FEP, ATM, AMK, GEN, CIP NDM-1, CTX-M-15, TEM, SHV ∼50 UT Tc-ES49a — 2 2 S CAZ, CTX, FEP NDM-1 ∼50 IncFII ES69 11 8 8 8 CAZ, CTX, FEP, ATM, GEN, CIP, CST OXA-48, CTX-M-15, TEM, SHV ∼39 UT Tc-ES69a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES94 893 8 8 256 CAZ, CTX, FEP, ATM, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 10 IncL/M Tc-ES94a — 4 4 2 CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ES132 147 8 8 8 CAZ, CTX, FEP, ATM, AMK, GEN, CIP OXA-48, NDM-1, CTX-M-15, TEM, SHV ∼39 and 4 UT Tc-ES132a — 2 2 S CAZ, CTX, FEP, ATM OXA-48, CTX-M-15, TEM ∼39 IncL/M ETP, ertapenem; MEM, meropenem; IPM, imipenem; CAZ, ceftazidime; CTX, cefotaxime; FEP, cefepime; ATM, aztreonam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; FOF, fosfomycin; CST, colistin; UT, untypeable. a Tc, E. coli K12 transconjugant selected in medium containing 1 mg/L meropenem. Plasmid analysis indicated that blaOXA-48 in transconjugants Tc-ES39 and Tc-ES69 was located on ∼39 kb IncL/M conjugative plasmids (Table 2); the two plasmids showed identical profiles after HindIII digestion (data not shown). In Tc-ES49, blaNDM-1 was found on a ∼50 kb IncFII conjugative plasmid. Transconjugants Tc-ES132 and Tc-ES94 each contained a single plasmid; the two plasmids had distinct restriction profiles (data not shown). Transconjugants Tc-ES132 and Tc-ES94 were only positive for blaOXA-48, blaCTX-M-15 and blaTEM genes, whereas they were negative for the blaNDM-1 gene. In initial isolates of ES94 and ES132, plasmid gel extraction followed by PCR amplification revealed that the blaOXA-48 gene was harboured on a transferable plasmid of ∼39 kb belonging to the IncL/M incompatibility group, whereas the blaNDM-1 gene was carried on a non-conjugative plasmid of ∼4 or 10 kb. Discussion This study highlights the finding of CPKP with blaOXA-48 and blaNDM-1 genes together or alone, in a hospital in Isfahan. The co-occurrence of OXA-48- and NDM-1-producing K. pneumoniae has been reported in some Asian and European countries.1,3,23,24 In this hospital, blaNDM-1 was first isolated in March 201316 and the prevalence of blaNDM-1-producing K. pneumoniae isolates collected at this hospital increased from 12.2% in 2013–14 to 41.7% in 2015–16 (our study). In addition, our previous study in this hospital showed that intestinal carriage rates of NDM-1- and OXA-48-producing Enterobacteriaceae are high, suggesting that NDM-1 and OXA-48 have become endemic.25 In addition to recent observations in neighbouring countries (Kuwait26 and Lebanon9), this indicates the emergence of this resistance mechanism in the Middle East. Analysis of transconjugants revealed that the blaOXA-48 gene, together with blaCTX-M-15 and blaTEM, were carried on ∼39 kb transferable plasmids belonging to the IncL/M incompatibility group, in accordance with other studies showing that blaOXA-48 was carried by an epidemic plasmid worldwide.1,3 Previous studies have reported that the spread of blaNDM-1 is linked to different types of IncA/C, IncF, IncN and untypeable plasmids.6,27 We found Tc-ES49 carrying blaNDM-1 in a ∼50 kb IncFII plasmid (Table 2). Transferable IncL/M and IncFII plasmids have greatly contributed to the dissemination of antibiotic resistance genes such as blaOXA-48, blaNDM-1 and blaCTX-M-15 among K. pneumoniae, but they also have the ability to transfer between other enterobacterial species.6,28,29 In the present study, pulsotype A (n = 47) and pulsotype B (n = 29) corresponded to ST11 and ST893, respectively (Figure 1). ST11 and ST893 have been circulating in this hospital setting during the period of investigation, indicating two separate outbreaks, with the ICU acting as the epicentre. Interestingly, two clones were overlapping and most isolates were identified in February 2015. Hospital outbreaks linked to CPKP have been previously reported and are likely associated with particular clonal lineages, similar to our study.3,29 Therefore, it is crucial to identify the clonal relatedness among the CPKP to strengthen the surveillance and reporting system in hospital infection control measures. ST11 (47 pulsotype A and 1 singleton) was the predominant CPKP that disseminated across 10 wards. All ST11 isolates carried the blaOXA-48 gene, whereas six isolates of ST11 co-produced blaOXA-48 and blaNDM-1 genes. ST11 is a single-locus variant of the pandemic ST258 clone and it was considered a high-risk epidemic clone owing to its ability to spread rapidly and disseminate β-lactamases (such as ESBLs and carbapenemases). In the present study, the majority of ST11 isolates carried OXA-48 and CTX-M-15 genes. Previous studies have also identified a high frequency of association between CTX-M-15 and OXA-48 or NDM-1 in ST11 isolates.1,3,6 ST893 (29 pulsotype B and 2 pulsotype C) was the second most common ST in our study and was isolated from patients in six different wards. Overall, co-existence of blaOXA-48 and blaNDM-1 genes among this clone was found to be 77.4% (24/31). The co-production of these two genes in ST893 accounted for its high resistance to carbapenems (Table 1). ST893 has only been reported in China and has not been associated with ESBLs or carbapenemases.30 In our study, five minor pulsotypes were also observed (C, D, E, F and G). Pulsotype C included the two ST893 isolates. ST147 (pulsotypes E and F) that harboured an IncFII plasmid and was positive for blaNDM-1 and ESBL genes was isolated from four patients on three different wards. Also, two NDM-1-positive ST147 isolates produced OXA-48. The ST147 isolates have been identified in OXA-48 and OXA-204 producers in France31,32 and China3 and also reported in NDM-1 producers in Tunisia33 and Oman.34 ST915 (pulsotype G) carried the blaNDM-1 gene, which was isolated from two patients on two different wards. The most remarkable finding from our study is that the ST893 and ST915 clones have not been previously linked with NDM and OXA-48 production and are not clustered with any of the high-risk clones previously associated with these enzymes, which could indicate that the spread of carbapenemases is evolving towards new STs. In conclusion, a clonal dissemination and outbreak of OXA-48- and NDM-1-producing K. pneumoniae that co-produce ESBLs has been observed. ST11 and ST893 K. pneumoniae were the predominant clones that were associated with the two separate outbreaks and harboured a host narrow-range IncFII plasmid of ∼50 kb or broad-range IncL/M plasmid of ∼39 kb. There is no doubt the emergence and spread of NDM-1 and OXA-48 in K. pneumoniae will further limit clinical therapeutic options and threaten the public health of Iran. It is crucial that strict infection control measures should be adopted to control CPKP outbreaks in our clinical settings. Acknowledgements We would like to thank the personnel of the Bacteriology Department of the Pasteur Institute of Iran for their assistance and Muhammad Humaun Kabir for excellent technical assistance. Funding This work was funded by research grants from the Pasteur Institute of Iran (project no. IR.PII.REC.1395.51). Transparency declarations None to declare. References 1 Brãnas P , Villa J , Viedma E et al. 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NDM-1, OXA-48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate of Oman . Clin Microbiol Infect 2012 ; 18 : 144 – 8 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Journal of Antimicrobial ChemotherapyOxford University Press

Published: Mar 6, 2018

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