A Polyclonal Spread Emerged: Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates from the Intensive Care Unit in a Chinese Tertiary Hospital

WANG, ZHENGZHENG; YU, FANGYOU; SHEN, XIAOFEI; LI, MEILAN

doi:10.33073/pjm-2020-034

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates often cause nosocomial infections with limited therapeutic options and spread rapidly worldwide. In this study, we revealed a polyclonal emergence of CRKP isolates from the intensive care unit in a Chinese tertiary hospital. We applied a series of methods including automated screening, antimicrobial susceptibility testing, the modified carbapenem inacti vation method (mCIM), PCR amplification, DNA sequencing, and multilocus sequence typing (MLST) to characterize 30 non-duplicated CRKP isolates along with the collection of the related medical records. The results showed the polyclonal spread of CRKP isolates belonged to ST722, ST1446, ST111, ST896, ST290, and ST11. Among them, ST722 and ST1446 were two novel types of K. pneumoniae, and ST896 isolate harboring bla_KPC-2 was also found for the first time. Since the polyclonal spread of CRKP in the same ward is rare, the silent clonal evolution with the switching genotypes prompts us to stay alert for outbreaks caused by novel subclones.

References

Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J. Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin Infect Dis. 2004 Jul 01;39(1): 55–60. https://doi.org/10.1086/421495
Search in Google Scholar Back to article
Bratu S, Landman D, Haag R, Recco R, Eramo A, Alam M, Quale J. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch Intern Med. 2005 Jun 27;165(12):1430–1435. https://doi.org/10.1001/archinte.165.12.1430
Search in Google Scholar Back to article
Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010 Mar;54(3):969–976. https://doi.org/10.1128/AAC.01009-09
Search in Google Scholar Back to article
CLSI. Performance standards for antimicrobial susceptibility testing, 28th Inforational Supplement (M100-S28). Wayne (USA): Clinical and Laboratory Standards Institute; 2018.
Search in Google Scholar Back to article
Debby BD, Ganor O, Yasmin M, David L, Nathan K, Ilana T, Dalit S, Smollan G, Galia R. Epidemiology of carbapenem resistant Klebsiella pneumoniae colonization in an intensive care unit. Eur J Clin Microbiol Infect Dis. 2012 Aug;31(8):1811–1817. https://doi.org/10.1007/s10096-011-1506-5
Search in Google Scholar Back to article
Diago-Navarro E, Chen L, Passet V, Burack S, Ulacia-Hernando A, Kodiyanplakkal RP, Levi MH, Brisse S, Kreiswirth BN, Fries BC. Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. J Infect Dis. 2014 Sep 01;210(5):803–813. https://doi.org/10.1093/infdis/jiu157
Search in Google Scholar Back to article
Diancourt L, Passet V, Verhoef J, Grimont PAD, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005 Aug 01;43(8):4178–4182. https://doi.org/10.1128/JCM.43.8.4178-4182.2005
Search in Google Scholar Back to article
Filgona J, Banerjee T, Anupurba S. Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India. J Infect Dev Ctries. 2015 Aug 29;9(08):815–820. https://doi.org/10.3855/jidc.6216
Search in Google Scholar Back to article
Gong X, Zhang J, Su S, Fu Y, Bao M, Wang Y, Zhang X. Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the Eastern region of Heilongjiang Province, China. BMC Infect Dis. 2018 Dec;18(1):417. https://doi.org/10.1186/s12879-018-3294-3
Search in Google Scholar Back to article
Hammerum AM, Hansen F, Lester CH, Jensen KT, Hansen DS, Dessau RB. Detection of the first two Klebsiella pneumoniae isolates with sequence type 258 producing KPC-2 carbapenemase in Denmark. Int J Antimicrob Agents. 2010 Jun;35(6):610–612. https://doi.org/10.1016/j.ijantimicag.2010.01.024
Search in Google Scholar Back to article
Hu L, Liu Y, Deng L, Zhong Q, Hang Y, Wang Z, Zhan L, Wang L, Yu F. Outbreak by ventilator-associated ST11 K. pneumoniae with co-production of CTX-M-24 and KPC-2 in a SICU of a tertiary teaching hospital in central China. Front Microbiol. 2016 Aug 02; 7:1190. https://doi.org/10.3389/fmicb.2016.01190
Search in Google Scholar Back to article
Hussein K, Sprecher H, Mashiach T, Oren I, Kassis I, Finkelstein R. Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns. Infect Control Hosp Epidemiol. 2009 Jul;30(7):666–671. https://doi.org/10.1086/598244
Search in Google Scholar Back to article
Ji S, Lv F, Du X, Wei Z, Fu Y, Mu X, Jiang Y, Yu Y. Cefepime combined with amoxicillin/clavulanic acid: a new choice for the KPC-producing K. pneumoniae infection. Int J Infect Dis. 2015 Sep;38:108–114. https://doi.org/10.1016/j.ijid.2015.07.024
Search in Google Scholar Back to article
Kaczmarek FM, Dib-Hajj F, Shang W, Gootz TD. High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is due to the combination of bla(ACT-1) beta-lactamase production, porin OmpK35/36 insertional inactivation, and down-regulation of the phosphate transport porin phoe. Antimicrob Agents Chemother. 2006 Oct;50(10):3396–3406. https://doi.org/10.1128/AAC.00285-06
Search in Google Scholar Back to article
Kitchel B, Rasheed JK, Patel JB, Srinivasan A, Navon-Venezia S, Carmeli Y, Brolund A, Giske CG. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob Agents Chemother. 2009 Aug;53(8):3365–3370. https://doi.org/10.1128/AAC.00126-09
Search in Google Scholar Back to article
Kofteridis DP, Valachis A, Dimopoulou D, Maraki S, Christidou A, Mantadakis E, Samonis G. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: A case-case-control study. J Infect Chemother. 2014 May;20(5):293–297. https://doi.org/10.1016/j.jiac.2013.11.007
Search in Google Scholar Back to article
Kumar M, Shankar C, Baskaran A, Paul M, Ponmudi N, Santhanam S, Michael J, Veeraraghavan B. Molecular characterisation for clonality and transmission dynamics of an outbreak of Klebsiella pneumoniae amongst neonates in a tertiary care centre in South India. Indian J Med Microbiol. 2018;36(1):54–60. https://doi.org/10.4103/ijmm.IJMM_17_426
Search in Google Scholar Back to article
Lester CH, Olsen SS, Jakobsen L, Arpi M, Fuursted K, Hansen DS, Heltberg O, Holm A, Højbjerg T, Jensen KT, et al. Emergence of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in Danish hospitals; this is in part explained by spread of two CTX-M-15 clones with multilocus sequence types 15 and 16 in Zealand. Int J Antimicrob Agents. 2011 Aug;38(2):180–182. https://doi.org/10.1016/j.ijantimicag.2011.03.018
Search in Google Scholar Back to article
Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: The impact and evolution of a global menace. J Infect Dis. 2017. 215(suppl_1):S28-S36.
Search in Google Scholar Back to article
Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, et al.; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014 Mar 27;370(13):1198–1208. https://doi.org/10.1056/NEJMoa1306801
Search in Google Scholar Back to article
Maltezou HC, Giakkoupi P, Maragos A, Bolikas M, Raftopoulos V, Papahatzaki H, Vrouhos G, Liakou V, Vatopoulos AC. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J Infect. 2009 Mar;58(3):213–219. https://doi.org/10.1016/j.jinf.2009.01.010
Search in Google Scholar Back to article
Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Front Cell Infect Microbiol. 2018 Jan 22;8:4. https://doi.org/10.3389/fcimb.2018.00004
Search in Google Scholar Back to article
Mathers AJ, Peirano G, Pitout JDD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev. 2015 Jul;28(3):565–591. https://doi.org/10.1128/CMR.00116-14
Search in Google Scholar Back to article
Nordmann P, Poirel L, Carrër A, Toleman MA, Walsh TR. How to detect NDM-1 producers. J Clin Microbiol. 2011 Feb 01;49(2): 718–721. https://doi.org/10.1128/JCM.01773-10
Search in Google Scholar Back to article
Papadimitriou-Olivgeris M, Marangos M, Fligou F, Christofidou M, Sklavou C, Vamvakopoulou S, Anastassiou ED, Filos KS. KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality. Diagn Microbiol Infect Dis. 2013 Oct;77(2):169–173. https://doi.org/10.1016/j.diagmicrobio.2013.06.007
Search in Google Scholar Back to article
Qi Y, Wei Z, Ji S, Du X, Shen P, Yu Y. ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J Antimicrob Chemother. 2011 Feb;66(2):307–312. https://doi.org/10.1093/jac/dkq431
Search in Google Scholar Back to article
Queenan AM, Bush K. Carbapenemases: the versatile β-Lactamases. Clin Microbiol Rev. 2007 Jul;20(3):440–458. https://doi.org/10.1128/CMR.00001-07
Search in Google Scholar Back to article
Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother. 2008 Mar;52(3):1028–1033. https://doi.org/10.1128/AAC.01020-07
Search in Google Scholar Back to article
Snitkin ES, Zelazny AM, Thomas PJ, Stock F, Henderson DK, Palmore TN, Segre JA; NISC Comparative Sequencing Program Group. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med. 2012 Aug 22;4(148):148ra116. https://doi.org/10.1126/scitranslmed.3004129
Search in Google Scholar Back to article
Tian L, Zhang Z, Sun Z. Antimicrobial resistance trends in bloodstream infections at a large teaching hospital in China: a 20-year surveillance study (1998–2017). Antimicrob Resist Infect Control. 2019 Dec;8(1):86. https://doi.org/10.1186/s13756-019-0545-z
Search in Google Scholar Back to article
uz Zaman T, Aldrees M, Al Johani SM, Alrodayyan M, Aldughashem FA, Balkhy HH. Multi-drug carbapenem-resistant Klebsiella pneumoniae infection carrying the OXA-48 gene and showing variations in outer membrane protein 36 causing an outbreak in a tertiary care hospital in Riyadh, Saudi Arabia. Int J Infect Dis. 2014 Nov;28:186–192. https://doi.org/10.1016/j.ijid.2014.05.021
Search in Google Scholar Back to article
Vardakas KZ, Matthaiou DK, Falagas ME, Antypa E, Koteli A, Antoniadou E. Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. J Infect. 2015 Jun;70(6):592–599. https://doi.org/10.1016/j.jinf.2014.11.003
Search in Google Scholar Back to article
Wang Z, Li M, Shen X, Wang L, Liu L, Hao Z, Duan J, Yu F. Outbreak of blaNDM-5 -Harboring Klebsiella pneumoniae ST290 in a Tertiary Hospital in China. Microb Drug Resist. 2019 Dec 01;25(10):1443–1448. https://doi.org/10.1089/mdr.2019.0046
Search in Google Scholar Back to article
WHO. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics [Internet]. Geneva (Switzerland): World Health Organization; 2017 [cited 2017 February 27]. Available from https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/
Search in Google Scholar Back to article
Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. NDM metallo-β-Lactamases and their bacterial producers in health care settings. Clin Microbiol Rev. 2019 Jan 30;32(2):e00115-18. https://doi.org/10.1128/CMR.00115-18
Search in Google Scholar Back to article
Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009 Dec;53(12): 5046–5054. https://doi.org/10.1128/AAC.00774-09
Search in Google Scholar Back to article
Yu F, Hu L, Zhong Q, Hang Y, Liu Y, Hu X, Ding H, Chen Y, Xu X, Fang X, et al. Dissemination of Klebsiella pneumoniae ST11 isolates with carbapenem resistance in integrated and emergency intensive care units in a Chinese tertiary hospital. J Med Microbiol. 2019 Jun 01;68(6):882–889. https://doi.org/10.1099/jmm.0.000981
Search in Google Scholar Back to article
Yu F, Ying Q, Chen C, Li T, Ding B, Liu Y, Lu Y, Qin Z, Parsons C, Salgado C, et al. Outbreak of pulmonary infection caused by Klebsiella pneumoniae isolates harbouring blaIMP-4 and blaDHA-1 in a neonatal intensive care unit in China. J Med Microbiol. 2012 Jul 01;61(7):984–989. https:0/doi.org/10.1099/jmm.0.043000-0
Search in Google Scholar Back to article
Zhang P, Shi Q, Hu H, Hong B, Wu X, Du X, Akova M, Yu Y. Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China. Clin Microbiol Infect. 2020 Jan;26(1):124.e1-124.e4. https://doi.org/10.1016/j.cmi.2019.08.020
Search in Google Scholar Back to article
Zhang R, Wang XD, Cai JC, Zhou HW, Lv HX, Hu QF, Chen GX. Outbreak of Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae with high qnr prevalence in a Chinese hospital. J Med Microbiol. 2011 Jul 01;60(7):977–982. https://doi.org/10.1099/jmm.0.015826-0
Search in Google Scholar Back to article

A Polyclonal Spread Emerged: Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates from the Intensive Care Unit in a Chinese Tertiary Hospital

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