Abstract
Dissemination of carbapenemase-producing Klebsiella pneumoniae along with 16S rRNA methyltransferase (16S-RMTase) has been caused as a great concern for healthcare settings. The aim of this study was to investigate the prevalence of resistance genes among K. pneumoniae isolates. During October 2015 to February 2016, 30 non-duplicative K. pneumoniae strains were isolated from clinical specimens in a burn center in Kerman, Iran. Antibiotic susceptibility tests of isolates, carbapenemase, extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamase-producing isolates were determined by phenotypic methods. The beta-lactamase, oqxA/B efflux pumps, qnr A, B, S, 16S-RMTase (rmt A, B, and C), and mcr-1 resistance genes were determined by PCR. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used for molecular typing. According to our findings, tigecycline has been shown the most active agent against K. pneumoniae isolates. Antibiotic resistance genes, blaTEM-1, blaSHV-12, blaCTX-M-15, blaCTX-M-2, blaNDM-1, blaFOX, blaMOX, blaEBC, blaACC, blaCIT, rmtC, qnrB, qnrS, oqxA, and oqxB, were detected in 11 (36.7%), 13 (43.3%), 11 (36.6%), 5 (16.6%), 9 (30%), 1 (3.3%), 1 (3.3%), 1 (3.3%), 1 (3.3%), 2 (6.7%), 1 (3.3%), 9 (30%), 2 (6.7%), 18 (60%), and 13 (43.3%) of isolates, respectively. The blaNDM-1 with rmtC was simultaneously observed in one isolate. ERIC-PCR results revealed 25 distinct patterns in eight clusters (A–H) and five singletons. This study highlights the high prevalence of blaNDM and emergence of rmtC among carbapenem-resistant K. pneumoniae. The resistance genes are often co-located on the conjugative plasmids, so it might be the reason of the rapid spread of them. The prevalence of multidrug-resistant K. pneumoniae isolates limits the available treatment options and presents tremendous challenges to public health.
Similar content being viewed by others
References
Azadpour M, Soleimani Y, Rezaie F, Nikanpour E, Mahmoudvand H, Jahanbakhsh S (2014) Prevalence of qnr genes and antibiotic susceptibility patterns among clinical isolates of Klebsiella Pneumoniae in west of Iran. J Bacteriol Parasitol 5:1000202
Azimi L, Nordmann P, Lari AR, Bonnin RA (2014) First report of OXA-48-producing Klebsiella pneumoniae strains in Iran. GMS Hyg Infect Control 9:Doc07
Ben-Hamouda T, Foulon T, Ben-Cheikh-Masmoudi A, Fendri C, Belhadj O, Ben-Mahrez K (2003) Molecular epidemiology of an outbreak of multiresistant Klebsiella pneumoniae in a Tunisian neonatal ward. J Med Microbiol 52:427–433
Black JA, Moland ES, Thomson KS (2005) AmpC disk test for detection of plasmid-mediated AmpC β -lactamases in Enterobacteriaceae lacking chromosomal AmpC β-lactamases. J Clin Microbiol 43:3110–3113
British Society of Antimicrobial Chemotherapy (BSAC) (2018) BSAC to actively support the EUCAST disc diffusion method for antimicrobial susceptibility testing in preference to the current BSAC disc diffusion method. http://www.bsac.org.uk
Bueno MF, Francisco GR, O'Hara JA, de Oliveira Garcia D, Doi Y (2013) Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum β lactamases in Klebsiella pneumoniae. Antimicrob Agents Chemother 57:2397–2400
Cantón R, Akóva M, Carmeli Y, Giske CG, Glupczynski Y, Gniadkowski M, Livermore DM, Miriagou V, Naas T, Rossolini GM, Samuelsen Ø (2012) Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clin Microbiol Infect 18:413–431
Cha MK, Kang CI, Kim SH, Chung DR, Peck KR, Lee NY, Song JH (2018) High prevalence of CTX-M-15-type extended-spectrum β-lactamase among AmpC β-lactamase-producing Klebsiella pneumoniae isolates causing bacteremia in Korea. Microb Drug Resist. https://doi.org/10.1089/mdr.2017.0362
Cheddie P, Dziva F, Akpaka PE (2017) Detection of a CTX-M group 2 beta-lactamase gene in a Klebsiella pneumoniae isolate from a tertiary care hospital, Trinidad and Tobago. Ann Clin Microbiol Antimicrob 16:33
CLSI (2017) Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute
Daoud Z, Salem Sokhn E, Masri K, Cheaito K, Haidar-Ahmad N, Matar GM, Doron S (2015) Escherichia coli isolated from urinary tract infections of Lebanese patients between 2005 and 2012: epidemiology and profiles of resistance. Front Med 2:26
European Committee on Antimicrobial Susceptibility Testing (2018) Breakpoints tables for interpretation of MICs and zones diametersVersion 8.0. http://www.eucast.org/clinical_breakpoints
Feizabadi MM, Delfani S, Raji N, Majnooni A, Aligholi M, Shahcheraghi F, Parvin M, Yadegarinia D (2010) Distribution of bla TEM, bla SHV, bla CTX-M genes among clinical isolates of Klebsiella pneumoniae at Labbafinejad Hospital, Tehran, Iran. Microb Drug Resist 16:49–53
Fritsche TR, Castanheira M, Miller GH, Jones RN, Armstrong ES (2008) Detection of methyltransferases conferring high-level resistance to aminoglycosides in Enterobacteriaceae from Europe, North America, and Latin America. Antimicrob Agents Chemother 52:1843–1845
Guo Y, Zhou H, Qin L, Pang Z, Qin T, Ren H, Pan Z, Zhou J (2016) Frequency, antimicrobial resistance and genetic diversity of Klebsiella pneumoniae in food samples. PLoS One 11:e0153561
Hansen LH, Jensen LB, Sørensen HI, Sørensen SJ (2007) Substrate specificity of the OqxAB multidrug resistance pump in Escherichia coli and selected enteric bacteria. J Antimicrob Chemother 60:145–147
Helmy MM, Wasfi R (2014) Phenotypic and molecular characterization of plasmid mediated AmpC β-lactamases among Escherichia coli, Klebsiella spp., and Proteus mirabilis isolated from urinary tract infections in Egyptian hospitals. Biomed Res Int 2014:171548
Hernández-Allés S, Benedí VJ, Martínez-Martínez L, Pascual Á, Aguilar A, Tomás JM, Albertí S (1999) Development of resistance during antimicrobial therapy caused by insertion sequence interruption of porin genes. Antimicrob Agents Chemother 43:937–939
Hidalgo L, Hopkins KL, Gutierrez B, Ovejero CM, Shukla S, Douthwaite S, Prasad KN, Woodford N, Gonzalez-Zorn B (2018) Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. J Antimicrob Chemother 68:1543–1550
Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332
Hu L, Zhong Q, Shang Y, Wang H, Ning C, Li Y, Hang Y, Xiong J, Wang X, Xu Y, Qin Z (2014) The prevalence of carbapenemase genes and plasmid-mediated quinolone resistance determinants in carbapenem-resistant Enterobacteriaceae from five teaching hospitals in Central China. Epidemiol Infect 142:1972–1977
Jiang Y, Yu D, Wei Z, Shen P, Zhou Z, Yu Y (2010) Complete nucleotide sequence of Klebsiella pneumoniae multidrug resistance plasmid pKP048, carrying bla KPC-2, bla DHA-1, qnrB4, and armA. Antimicrob Agents Chemother 54(9):3967
Kim HB, Wang M, Park CH, Kim EC, Jacoby GA, Hooper DC (2009) oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob Agents Chemother 53:3582–3584
Lee CH, Chu C, Liu JW, Chen YS, Chiu CJ, Su LH (2007) Collateral damage of flomoxef therapy: in vivo development of porin deficiency and acquisition of bla DHA-1 leading to ertapenem resistance in a clinical isolate of Klebsiella pneumoniae producing CTX-M-3 and SHV-5 β-lactamases. J Antimicrob Chemother 60:410–413
Liu JH, Deng YT, Zeng ZL, Gao JH, Chen L, Arakawa Y, Chen ZL (2008) Coprevalence of plasmid-mediated quinolone resistance determinants QepA, Qnr, and AAC(6′)-Ib-cr among 16S rRNA methylase RmtB-producing Escherichia coli isolates from pigs. Antimicrob Agents Chemother 52:2992–2993
Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, LF( Y (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168
Mahon CR, Lehman DC, Manuselis G (2007) Text book of diagnostic microbiology. 3rd ed. Philadelphia, PA, USA
Meacham KJ, Zhang L, Foxman B, Bauer RJ, Marrs CF (2003) Evaluation of genotyping large numbers of Escherichia coli isolates by enterobacterial repetitive intergenic consensus-PCR. J Clin Microbiol 41:5224–5226
Messai Y, Iabadene H, Benhassine T, Alouache S, Tazir M, Gautier V, Arlet G, Bakour R (2008) Prevalence and characterization of extended-spectrum β-lactamases in Klebsiella pneumoniae in Algiers hospitals (Algeria). Pathol Biol 56:319–325
Monstein HJ, Östholm-Balkhed Å, Nilsson MV, Nilsson M, Dornbusch K, Nilsson LE (2007) Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae. Apmis 115:1400–1408
Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K (2013) Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13:785–796
Nobari S, Shahcheraghi F, Rahmati Ghezelgeh F, Valizadeh B (2014) Molecular characterization of carbapenem-resistant strains of Klebsiella pneumoniae isolated from Iranian patients: first identification of bla KPC gene in Iran. Microb Drug Resist 20:285–293
Nordmann P, Cuzon G, Naas T (2009) The real threat of Klebsiella pneumoniae carbapenemase- producing bacteria. Lancet Infect Dis 9:228–236
Nordmann P, Poirel L, Walsh TR, Livermore DM (2011) The emerging NDM carbapenemases. Trends Microbiol 19:588–595
Pérez-Pérez FJ, Hanson ND (2002) Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 40:2153–2162
Poirel L, Walsh TR, Cuvillier V, Nordmann P (2011) Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 70:119–123
Qin S, Zhou M, Zhang Q, Tao H, Ye Y, Chen H, Xu L, Xu H, Wang P, Feng X (2016) First identification of NDM-4-producing Escherichia coli ST410 in China. Emerg Microbes Infect 5:e118
Quan J, Li X, Chen Y, Jiang Y, Zhou Z, Zhang H, Sun L, Ruan Z, Feng Y, Akova M, Yu Y (2017) Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China a multicenter longitudinal study. Lancet Infect Dis 7:400–410
Robicsek A, Strahilevitz J, Sahm DF, Jacoby GA, Hooper DC (2012) qnr prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. Antimicrob Agents Chemother 50:2872–2874
Ruiz E, Sáenz Y, Zarazaga M, Rocha-Gracia R, Martínez-Martínez L, Arlet G, Torres C (2012) Qnr, aac(6′)-ib-cr and qepA genes in Escherichia coli and Klebsiella spp.: genetic environments and plasmid and chromosomal location. J Antimicrob Chemother 67:886–897
Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME (2012) Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis 31:695–701
Shibl A, Senok A, Memish Z (2012) Infectious diseases in the Arabian peninsula and Egypt. Clin Microbiol Infect 18:1068–1080
Shibl A, Al-Agamy M, Memish Z, Senok A, Khader SA, Assiri A (2013) The emergence of OXA-48- and NDM-1-positive Klebsiella pneumoniae in Riyadh, Saudi Arabia. Int J Infect Dis 17:e1130–e1133
Toleman MA, Walsh TR (2011) Combinatorial events of insertion sequences and ICE in Gram-negative bacteria. FEMS Microbiol Rev 35:912–935
Wachino JI, Yamane K, Kimura K, Shibata N, Suzuki S, Ike Y, Arakawa Y (2006) Mode of transposition and expression of 16S rRNA methyltransferase gene rmtC accompanied by ISEcp1. Antimicrob Agents Chemother 50:3212–3215
Wasfi R, Elkhatib WF, Ashour HM (2016) Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep 22:38929
Yun-Tae K, Kim T, Baik HS (2006) Characterization of extended spectrum β-lactamase genotype TEM, SHV, and CTX-M producing Klebsiella pneumoniae isolated from clinical specimens in Korea. J Microbiol Biotechnol 16:889–895
Funding
This research was supported by the Kerman University of Medical Sciences and health services (grant no. 95000056).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethic approval code
This study was approved by ethical committee of Kerman University of Medical Sciences. The ethic approval code is IR.KMU.REC.1395.436.
Rights and permissions
About this article
Cite this article
Kiaei, S., Moradi, M., Hosseini Nave, H. et al. Emergence of co-existence of blaNDM with rmtC and qnrB genes in clinical carbapenem-resistant Klebsiella pneumoniae isolates in burning center from southeast of Iran. Folia Microbiol 64, 55–62 (2019). https://doi.org/10.1007/s12223-018-0630-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12223-018-0630-3