Characterization of Klebsiella pneumoniae Coproducing KPC and NDM-1 Carbapenemases from Turkey

Abstract

Aims:

The emergence of multidrug-resistant and carbapenem-resistant Klebsiella pneumoniae has became a major public health threat. In this study, we describe the characteristics of isolates coproducing KPC and NDM-1 carbapenemases from patients hospitalized at an emergency unit in Ankara, Turkey, between January and August 2018. The isolates were characterized by antibiogram susceptibility, carbapenemase and extended-spectrum beta-lactamase production, plasmid-mediated colistin (COL) resistance, and high-level aminoglycoside resistance. Pulsed field gel electrophoresis (PFGE), sequencing, wzi typing, multilocus sequence typing, and plasmid analysis were used to investigate the epidemiological relationship between the isolates.

Results:

All isolates were found to be resistant to amoxicillin–clavulanic acid, piperacillin–tazobactam, cefotaxime, cefoxitin, cefuroxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, amikacin, gentamicin, ciprofloxacin, levofloxacin, and trimethoprim–sulfamethoxazole. The minimum inhibitory concentration values for imipenem, meropenem, and ertapenem were >32 μg/mL, and >256 μg/mL for amikacin and gentamicin, and two isolates were found to be susceptible to both tigecycline and COL. All strains were positive for SHV, CTX-M, and rmtC, and negative for mcr-1 genes. A/C and FIIA_S plasmids were found in all isolates. All isolates had the same PFGE pattern: wzi type 93 and ST15.

Conclusion:

Here, we have documented the characteristics of KPC- and NDM-1-coproducing isolates that harbored SHV, CTX-M, and rmtC and were typed as wzi 93 and ST15. We conclude that continuous monitoring of carbapenemases for unusual carbapenemase production is crucial to prevent the spread of these powerful isolates.

Introduction

Klebsiella pneumoniae, a member of the Enterobacteriaceae family, is naturally present in the human and animal gastrointestinal tract. However, K. pneumoniae is also one of the most common etiological agents of life-threatening infections, such as pneumonia, septicemia, meningitis, and device-associated infections. It is also an opportunistic pathogen responsible for nosocomial infections mainly in intensive care units.¹ K. pneumoniae strains are among the most successful resistance-developing bacteria, with the ability to acquire resistance genes through horizontal gene transfer, mediated mostly by plasmids and transposons.¹

Resistance to beta-lactams due to the production of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases has become a major problem for the treatment of K. pneumoniae infections. These enzymes confer resistance to nearly all beta-lactams except carbapenems. Therefore, treatment with carbapenems have so far been associated with the best clinical outcomes for these strains.^2,3 However, the extensive use of carbapenems has resulted in the evolution of plasmid-mediated carbapenemases in K. pneumoniae as well as other members of Enterobacteriaceae.⁴ Morbidity and mortality rates are high for infections involving carbapenem-resistant K. pneumoniae, with extremely limited treatment options, which include only a few antibiotics with uncertain in vivo efficacy and/or major side effects, such as polymyxins or fosfomycin.⁵

There are three important types of carbapenemase enzymes: (i) The KPC type, (ii) the OXA-48 type, and (iii) metallo-beta-lactamases (MBLs) including the VIM-, IMP-, and NDM-type enzymes.¹ KPC is capable of hydrolyzing a variety of β-lactams, including penicillins, cephalosporins, carbapenems, and aztreonam.¹ KPC-producing isolates mostly belong to the ST258 clone carrying the Tn4401 transposon and overexpressing the bla_KPC-2 gene. This specific clone has been found to be responsible for epidemics worldwide and linked to the global spread of KPC.^1,6,7 The OXA-48-type enzymes are most common in Mediterranean countries and are endemic in Turkey, with a high incidence rate of about 90%.^8,9 NDM-1-producing bacteria are more prevalent in the United Kingdom, India, and Pakistan, and have been reported for the first time in a leukemic Iranian patient hospitalized for allogeneic hematopoietic stem cell transplantation in Istanbul in 2012.¹⁰ Currently, MBLs seem to be the second most prevalent carbapenemase produced in the Enterobacteriaceae family isolates in Turkey, with a prevalence of about 20%.^9,11 NDM can hydrolyze all β-lactams including carbapenems with the exception of monobactams and is susceptible to EDTA, but not to clavulanic acid or other commercially available beta-lactamase inhibitors.^1,12

In this study, we analyze KPC- and NDM-1-coproducing K. pneumoniae isolates based on cases from the emergency and internal medicine intensive care units at our hospital and describe the characterization of the strains. To our knowledge, this is the first study of coproduction of KPC and NDM carbapenemases in K. pneumoniae isolates from Europe.

Materials and Methods

Patients

During a routine surveillance program at the Ankara University Ibn-i Sina Training and Research Hospital in 2018, 10 KPC- and NDM-1-coproducing K. pneumoniae were isolated between March and August 2018 from different clinical samples of 10 patients hospitalized at the emergency department (ED) and related clinics and were further investigated.

The patients were 36–90 (mean 72.6) years of age, with an F/M ratio of 1. The investigation of the hospital records of the patients revealed that all the patients visited the ED between January and August 2018 and were either discharged from the ED or moved to another clinic. Patient characteristics are presented in Table 1.

Table 1.

Characteristics of the Patients with Carbapenem-Resistant Klebsiella pneumoniae Isolates

Patient No.	Age, years	Sex	Clinics	First admission to the ED		Underlying disease	Clinical sample from which CRKP was isolated		Treatment	Outcome
Patient No.	Age, years	Sex	Clinics	Date	Diagnosis	Underlying disease	Date	Type	Treatment	Outcome
1	86	F	ED	January 26, 2018	UTI	Dementia, osteoporosis	March 7, 2018	Catheter urine	Ertapenem+colistin	Discharge March 21, 2018
2	76	M	Internal Medicine-ICU	January 16, 2018	Pneumoniae	COPD	March 12, 2018	ETA and Catheter urine	İmipenem+tigecycline+colistin<	Discharge March 21, 2018
3	81	M	ED	March 5, 2018	Seizure+UTI+infected diabetic foot wound	Colon CA, prostate CA, meningioma, diabetes mellitus, neurogenic bladder	March 16, 2018	Diabetic wound swab	Meropenem+colistin+tigecycline	Discharge March 21, 2018
4	36	M	ED	April 7, 2018	Seizure+infected decubitus wound	Anaplastic astrocytoma	April 14, 2018	Decubitus wound aspirate	Meropenem+tigecycline	Discharge April 19, 2018
5	85	F	ED	April 5, 2018	Pneumonia+infected decubitus wound	Dementia, hypertension, CVI-immobile for 4 years	April 10, 2018	Decubitus wound aspirate	Meropenem+colistin	Exitus April 21, 2018
6	49	F	Internal Medicine-ICU	March 30, 2018	Pneumonia	CVI, schizophrenia, epilepsy, COPD	May 4, 2018	Catheter urine	Meropenem+tigecycline	Discharge May 14, 2018
7	90	M	Internal Medicine-ICU	April 19, 2018	Aspiration pneumonia+UTI	Parkinson's disease, dementia, COPD, hypertension, gallbladder rupture-postoperative immobilization and gastric feeding for 2.5 years	May 16, 2018	CVC	Meropenem+colistin	Discharge June 4, 2018
8	85	F	Geriatrics	April 28, 2018	Uropneumosepsis	Diabetes mellitus, hypertension, intracranial hematoma-immobile for 3 months	June 6, 2018	Decubitus wound swab (sacral)	Meropenem+colistin	Discharge June 18, 2018
9	66	F	Infectious diseases	May 2, 2018	Pneumonia	Diabetes mellitus, hypertension, thalamic abscessus	August 9, 2018	Sputum	Colistin	Exitus August 22, 2018
10	72	M	ED	August 16, 2018	Colangitic abscessus	Diabetes mellitus, pancreas CA	August 16, 2018	Abscessus aspirate	Meropenem+colistin	Exitus August 20, 2018

CA, cancer; COPD, chronic obstructive pulmonary disease; CVC, central venous catheter; CVI, cerebrovascular incident; ED, emergency department; ETA, endotracheal aspirate; F, female; ICU, intensive care unit; M, male; UTI, urinary tract infection.

Isolates and antimicrobial susceptibility tests

Ten K. pneumonia were isolated in various clinical samples taken from the above-mentioned patients (Table 1). The isolates were recovered by routine cultures of the samples and analyzed using matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF MS; Bruker Daltonics, Bremen, Germany).

Antimicrobial susceptibilities were evaluated both with the Kirby–Bauer disk diffusion test and by using automated systems (Phoenix; Becton Dickinson) for amoxicillin–clavulanic acid, piperacillin–tazobactam, cefotaxime, cefoxitin, cefuroxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, amikacin, gentamicin, ciprofloxacin, levofloxacin, and trimethoprim–sulfamethoxazole. The results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2018 criteria (EUCAST breakpoint tables for interpretation of minimum inhibitory concentrations [MICs] and zone diameters, Version 8.0). Carbapenem and tigecycline (TIG) susceptibilities were identified using gradient strip tests (Etest; BioMérieux, France), and colistin (COL) susceptibilities using the ISO-standard broth microdilution method (20776-1) as recommended by the joint CLSI-EUCAST polymyxin breakpoints working group.¹³ Amikacin and gentamicin MIC values were further investigated using the broth microdilution test.

The ESBL production of the isolates were analyzed using cefepime-cefepime clavulanic acid disks (Becton Dickinson) according to the EUCAST guidelines.¹⁴ The carbapenemase production of the strains was evaluated using the modified carbapenem inactivation method¹⁵ and combination disk testing (Mastdiscs combi; Mast Diagnostics, Germany) and interpreted according to the manufacturer's instructions and using the EUCAST guidelines.¹⁴

Molecular detection of carbapenemase and ESBL genes

Carbapenemase genes bla_IMP, bla_VIM, bla_NDM, bla_SPM, bla_AIM, bla_DIM, bla_GIM, bla_SIM, bla_KPC, bla_BIC, and bla_OXA-48 were detected through the multiplex PCR protocols described by Poirel et al.¹⁶ For the detection of CTX-M, the protocol by Bonnet et al.¹⁷ was used. TEM and SHV were evaluated according to the protocol described by Taşlı and Bahar.¹⁸

Investigation for the presence of the mcr-1 gene

The mcr gene conferring resistance to COL was determined using the protocol described by Liu et al.¹⁹

Detection of 16S methyltransferase gene

16S methyltransferase genes: armA, rmtB, and rmtC were investigated using the method described by Doi and Arakawa.²⁰

Pulsed field gel electrophoresis

Pulsed field gel electrophoresis (PFGE) was performed to genotype the isolates according to CDC protocol using XbaI restriction endonuclease.²¹

Plasmid analysis

Plasmid groups were investigated using the multiplex PCR protocol described by Carattoli et al.²²

Identification of capsule type (wzi typing)

Capsular polysaccharide wzi gene sequencing was performed according to the method described by Brisse et al.²³ The allele number and putative serotypes were assigned based on the K. pneumoniae website.²⁴

Sequencing and multilocus sequence typing

The PCR products of the KPC and NDM-1 and the seven housekeeping genes (gapA, infB, mdh, pgi, phoE, rpoB, and tonB) were purified with ExoSAP-IT™ PCR Product Cleanup Reagent, and the housekeeping genes were sequenced according to the protocol by Diancourt et al.²⁵ using the ABI 3730 XL DNA Analyzer (Macrogen, Holland). The sequences of KPC and NDM were analyzed with the BLAST alignment tool of the National Center for Biotechnology Information,²⁶ and the sequence types of the isolates were identified using the multilocus sequence typing (MLST) database.²⁴

Results

Antimicrobial susceptibilities

All isolates were found to be resistant to amoxicillin–clavulanic acid, piperacillin–tazobactam, cefotaxime, cefoxitin, cefuroxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, amikacin, gentamicin, ciprofloxacin, levofloxacin, and trimethoprim–sulfamethoxazole. The MIC values for imipenem, meropenem, and ertapenem were all >32 μg/mL, and for amikacin and gentamicin, they were >256 μg/mL. Only two of the isolates were found to be susceptible to both TIG and COL. Of the eight remaining isolates, four were resistant to COL, two were resistant to TIG, and two were resistant to COL and intermediate to TIG, according to the 2018 EUCAST criteria. All the strains were ESBL and carbapenemase producers. The phenotypic characteristics of the isolates are presented in Table 2.

Table 2.

Phenotypic Characteristics of the Carbapenem-Resistant Klebsiella pneumoniae

Patient No.	Strain No.	Sample type	Resistance phenotype	ESBL production (DDT)	Carbapenemase production (CIM)	Combined disk test	Minimum inhibitory concentrations (μg/mL)
Patient No.	Strain No.	Sample type	Resistance phenotype	ESBL production (DDT)	Carbapenemase production (CIM)	Combined disk test	IMI	MEM	ETP	AK	GN	TIG	COL
1	M14468	Urine	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, TIG	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	4	0.5
2	M15495	Urine	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	1	8
3	M16593	Wound swab	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	1	8
4	M22623	Wound aspirate	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, TIG	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	8	0.5
5	M24043	Wound aspirate	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	2	64
6	M26747	Urine	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	1	4
7	M29156	CVC	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	0.5	64
8	M33301^a	Wound swab	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	1	1
9	M46874	Sputum	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ, COL	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	2	>64
10	M48383^a	Abscessus aspirate	AMC, PTZ, CTX, FOX, CXM, CAZ, FEP, IMI, MEM, ETP, AK, GN, CIP, LEV, TMP-SMZ	Positive	Positive	OXA-48	>32	>32	>32	>256	>256	0.5	0.125

TIG- and COL-susceptible isolates.

AK, amikacin; AMC, amoxicillin–clavulanic acid; CAZ, ceftazidime; CIM, carbapenem inactivation method; CIP, ciprofloxacin; COL, colistin; CTX, cefotaxime; CXM, cefuroxime; DDT, double disk test; ESBL, extended-spectrum beta-lactamase; ETP, ertapenem; FEP, cefepime; FOX, cefoxitin; GN, gentamicin; IMI, imipenem; LEV, levofloxacin; MEM, meropenem; PTZ, piperacillin–tazobactam; TIG, tigecycline; TMP-SMZ, trimethoprim–sulfamethoxazole.

Carbapenemase, ESBL, mcr, 16S methyltransferase genes

All isolates were positive for both NDM-1 and KPC carbapenemases and negative for OXA-48 and others. The isolates were positive for CTX M and SHV and negative for TEM. All the isolates were found to be negative for the mcr gene and positive for rmtC.

Plasmid analysis

All isolates had A/C and FIIA_S incompatibility plasmids.

PFGE, wzi typing, sequencing, and MLST

All isolates had the same PFGE profile, that is, wzi type 93 (K-type: K60); the sequences of NDM and KPC were concordant with NDM-1 and KPC-2, and all isolates were found as ST15 with MLST.

Discussion

Carbapenem-resistant K. pneumonia strains pose a significant public health threat as they can spread rapidly. Carbapenem resistance in Enterobacteriaceae usually arises as a result of two mechanisms: (i) deficiency of porin expression in combination with overexpression of beta-lactamases such as AmpC or ESBL, which exhibit a very weak affinity for carbapenems and (ii) production of carbapenemases. Carbapenem resistance in isolates with porin defects is unstable and of less clinical concern because these strains are usually less resistant to other antibiotic families. However, carbapenemase-mediated carbapenem resistance is of serious concern due to the high-level resistance of these strains not only to the beta-lactam group antibiotics but also to other classes such as aminoglycosides and fluoroquinolones. Infections involving these carbapenemase-producing strains are associated with more adverse clinical outcomes and higher mortality rates.¹

KPC enzymes are the most common and clinically significant carbapenemase enzymes produced by K. pneumoniae isolates. These strains are usually multidrug resistant with very limited therapeutic options, and mortality due to infections involving KPC-producing strains is known to be as high as 50%.¹ KPC enzymes, although identified in 2001²⁷ and reported in outbreaks all over the world since then, have not been reported in Turkey until 2014.²⁸ The first KPC-2-positive Escherichia coli isolate in Turkey was reported in 2016, and KPC enzymes are still rarely reported in carbapenemase-producing Enterobacteriaceae.^29,30

NDM-1-producing strains may express many other unrelated resistance genes to various classes of antimicrobials, leaving these strains susceptible only to TIG, COL, and fosfomycin. The attributable mortality of infections due to MBL-producing strains is reported as 18–67%.¹ The NDM-1 carbapenemase initially reported in India³¹ was introduced to our national repertory in 2011.¹⁰ Since 2011, the incidence of NDM-1-producing K. pneumoniae strains has increased, rapidly reaching 20% of identified carbapenemases in studies conducted in recent years.^9,11,32

To our knowledge, this is the first report of coproduction of KPC and NDM enzymes in clinical K. pneumoniae isolates and the increasing incidence of KPC-producing K. pneumoniae strains from Turkey. Six of our KPC- and NDM-producing strains were resistant to COL, two of which also exhibited intermediate resistance to TIG. Two were resistant to TIG, whereas only two were susceptible to both. Of the 10 patients from whom KPC- and NDM-producing strains were isolated, 3 died (mortality rate 33.3%), and the remaining 7 patients were discharged from the hospital.

The coproduction of KPC with other carbapenemases such as VIM and NDM in K. pneumoniae was reported in different countries, including Italy,³³ Greece,³⁴ and China,³⁵ indicating the worldwide distribution of K. pneumoniae co-harboring two carbapenemases. The coproduction of KPC-2 and NDM-1 was first observed in a K. pneumoniae isolate in India.³⁶ In Turkey, combinations of carbapenemases have particularly been found to include OXA-48 plus NDM, VIM, IMP, VIM, or KPC.^9,11,37–41

To the best of our knowledge, the coexistence of NDM-1 and KPC carbapenemases has not been reported in Europe. Still, it is always possible to observe the coproduction of different carbapenemases due to the nature and dissemination capacity of plasmids carrying these genes. ST258 isolates are linked to the dissemination of KPC carbapenemases,^42,43 and some sequence types such as ST258, 11, 15, 101, 147, 336, and 512 have come up often in worldwide epidemics/endemics.^6,7,44 It is well known that several KPC clones may spread—although varying by MLST type, beta-lactamase content, and plasmid types—within the same geographical area.¹

In Europe, most outbreaks related to KPC-2 production have been associated with ST258 isolates.⁴⁵ In a recent study, ST15 KPC-positive isolates were reported in Bulgaria.⁴⁶ The isolates in our study were also ST15 (1:1:1:1:1:1:1), the most prevalent ST producing CTX-M-type ESBLs. Our isolates were also found to be CTX-M and SHV positive. Sallouma et al.⁴⁷ have recently reported an NDM-1-producing ST15 K. pneumoniae isolated from a patient who was a refugee. Resistome analysis revealed the presence of several beta-lactamases including NDM-1, SHV-28, CTX-M-15, and OXA-1 in addition to armA gene in this isolate. They have also detected IncFIB(Mar), IncHI1B, IncFIB(pKPHS1), IncFIB(K), and IncFII(K) plasmids.

High-level aminoglycoside 16S methyltransferase-mediated resistance is transmitted by means of plasmids. 16S rRNA methyltransferases (RMTs), that is, armA, rmtA, rmtB1, rmtB2, rmtC, rmtD, rmtD2, rmtE, rmtF, rmtG, and rmtH, modify the G¹⁴⁰⁵ nucleotide and impact the activity of all 4.6-di-substituted aminoglycosides and NpmA, which modifies A¹⁴⁰⁸ impacts 4.5 and 4.6-disubstituted and monosubstituted aminoglycosides.⁴⁸ RmtC is first seen in Proteus mirabilis and then in Salmonella enterica Virchow strains and E. coli strains,⁴⁹ and is commonly seen with NDM-1-producing isolates especially in such diverse places as India, the United Kingdom,^50,51 Nepal,⁵² and Kenya.⁵³

The first report in Turkey is a study by Bercot et al.,⁵⁴ which investigated the presence of armA, rmtA, rmtB, rmtC, rmtD, and npmA genes in 70 isolates that were resistant at least to gentamicin and amikacin, of which 17 (16 E. coli and 1 K. pneumoniae) were also resistant to kanamycin, tobramycin, and netilmicin. Of the 17 aminoglycoside-resistant ESBL-producing Enterobacteriaceae, they found only 1 rmtB-positive isolate, which was K. pneumoniae. In Turkey, studies have indicated different 16S methylase genes in K. pneumoniae isolates. In 1 study, Gokmen et al.⁵⁵ investigated 40 isolates of K. pneumonia and performed PCR for 5 isolates with MIC values of >512 μg/mL for amikacin and >128 μg/mL for gentamicin, to find 4 isolates having rmtC that were also positive for NDM-1 carbapenemase. In another study, four NDM-1-positive K. pneumoniae isolates were found positive for rmtC, with one being ST15.³² In our study, all isolates were rmtC gene positive.

Plasmids belonging to the Inc F group and A/C groups are low-copy conjugative plasmids. Inc F group plasmids have limited host range and are seen in Enterobacteriaceae mainly found in E. coli with sizes ranging from 45 to 200 kb. Inc F plasmids carry resistance genes including genes encoding carbapenemases, ESBL genes, aminoglycoside-modifying enzymes, as well as plasmid-mediated quinolone resistance genes. A/C plasmids have a broad host range including members of Beta, Gamma, and Deltaproteobacteria with a size range of 40–320 kb and some smaller variants. A/C plasmids are associated with MDR and encode ESBLs, AmpC, carbapenemases such as OXA, NDM, and IMP, and enzymes modifying groups of antibiotics such as aminoglycosides, trimethoprim, tetracyclines, and chloramphhenicol.⁵⁶ Inc A/C, Inc L/M, Inc F, and some other plasmids play role in the dissemination of plasmid located blaNDM-1 and Inc F, IncL/M, and Inc N plasmid types for bla_KPC gene.⁵⁷ These data support the results of our study, which found that the NDM- and KPC-positive isolates investigated had both Inc A/C and Inc FIIA_S plasmids. Plasmid families including Inc A/C, Inc F, Inc N, IncX4, Inc K, and rolling circular replication plasmids are the sources of CTX-M genes.⁵⁷ A/C plasmids carry blaTEM and blaSHV but rarely CTX-M.⁵⁶ In our study, the isolates were found to be positive for CTX-M and SHV.

In sum, we have characterized the first K. pneumoniae isolates with KPC+NDM coproduction carbapenemases from a small outbreak that occurred in our hospital. These strains harbored 16S RNA methylase: rmtC and were typed as ST15 and wzi:93. This is the first report of the coexistence of NDM and KPC carbapenemases in Turkey. Our findings are important due to the unusual carbapenemase production and sequence type profiles. The continuous monitoring of carbapenemases is necessary to prevent the national and transnational spread of these powerful isolates.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

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