The emergence of clonally diverse carbapenem-resistant Enterobacter cloacae complex in West Bengal, India: a dockyard of β-lactamases periling nosocomial infections.

Publisher: Springer Nature Country of Publication: Switzerland NLM ID: 9816585 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-1905 (Electronic) Linking ISSN: 11396709 NLM ISO Abbreviation: Int Microbiol Subsets: MEDLINE

Publication: 2018- : Switzerland AG : Springer Nature
Original Publication: Barcelona, Spain : Springer, c1998-

beta-Lactamases*/genetics ; Enterobacteriaceae Infections*/microbiology ; Enterobacteriaceae Infections*/epidemiology ; Cross Infection*/microbiology ; Cross Infection*/epidemiology ; Anti-Bacterial Agents*/pharmacology ; Plasmids*/genetics ; Enterobacter cloacae*/genetics ; Enterobacter cloacae*/drug effects ; Enterobacter cloacae*/isolation & purification ; Enterobacter cloacae*/enzymology ; Microbial Sensitivity Tests*; India/epidemiology ; Humans ; Drug Resistance, Multiple, Bacterial/genetics ; Middle Aged ; Carbapenem-Resistant Enterobacteriaceae/genetics ; Carbapenem-Resistant Enterobacteriaceae/isolation & purification ; Carbapenem-Resistant Enterobacteriaceae/drug effects ; Carbapenem-Resistant Enterobacteriaceae/classification ; Adult ; Male ; Female ; Carbapenems/pharmacology ; Molecular Epidemiology ; Child ; Young Adult ; Aged ; Adolescent ; Child, Preschool ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Infant

Carbapenem-resistant Enterobacter cloacae complex (CRECC) constitutes a global public health threat challenging clinical treatment and infection control, especially in low- and middle-income countries such as India. We analyzed the antimicrobial susceptibility, major β-lactamase genes, plasmid profiles, and genetic relatedness to understand the molecular epidemiology of CRECC clinical isolates (n = 44) in West Bengal, India, during 2021-2022. The majority (> 55%) of the isolates were resistant to fluoroquinolones, aminoglycosides, and co-trimoxazole, even > 20% for tigecycline and > 35% were extensively drug-resistant. Co-β-lactamase production was categorized into twenty-seven types, importantly NDM (84%), OXA-48 (40%), TEM (61%), CTX-M (46%), OXA-1 (55%), and MIR (27%). The NDM-1 and OXA-181 were major variants with the first observations of NDM-24 and -29 variants in India. Wide-range of plasmids (2 to > 212 kb) were harbored by the β-lactamase-producing isolates: small (91%), medium (27%), large (9%), and mega (71%). IncX3, ColE1, and HI2 were noted in about 30% of isolates, while IncF and R were carried by < 20% of isolates. The clonally diverse CRECC isolates were noted to cause cross-infections, especially at superficial site, bloodstream, and urinary-tract. This is the first molecular surveillance on CRECC in India. The study isolates serve as the dockyard of NDM, TEM, and CTX-M harboring a wide range of plasmids. The outcomes of the study may strengthen local and national policies for infection prevention and control practices, clarifying the genetic diversity among CRECC. Extensive genomic study may further intersect the relationships between these different plasmids, especially with their sizes, types, and antibiotic resistance markers.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Annavajhala MK, Gomez-Simmonds A, Uhlemann AC (2019) Multidrug-resistant Enterobacter cloacae complex emerging as a global, diversifying threat. Front Microbiol 10:44. https://doi.org/10.3389/fmicb.2019.00044. (PMID: 10.3389/fmicb.2019.00044307665186365427)
Ares-Arroyo M, Bernabe-Balas C, Santos-Lopez A et al (2018) PCR-based analysis of ColE1 plasmids in clinical isolates and metagenomic samples reveals their importance as gene capture platforms. Front Microbiol 9:469. https://doi.org/10.3389/fmicb.2018.00469. (PMID: 10.3389/fmicb.2018.00469296159985864857)
Bolourchi N, Giske CG, Nematzadeh S et al (2022) Comparative resistome and virulome analysis of clinical NDM-1-producing carbapenem-resistant Enterobacter cloacae complex. J Glob Antimicrob Resist 28:254–263. https://doi.org/10.1016/j.jgar.2022.01.021. (PMID: 10.1016/j.jgar.2022.01.02135121164)
Cabral AB, Maciel MAV, Barros JF et al (2017) Clonal spread and accumulation of β-lactam resistance determinants in Enterobacter aerogenes and Enterobacter cloacae complex isolates from infection and colonization in patients at a public hospital in Recife, Pernambuco, Brazil. J Med Microbiol 66:70–77. https://doi.org/10.1099/jmm.0.000398. (PMID: 10.1099/jmm.0.00039827902398)
Carattoli A, Bertini A, Villa L et al (2005) Identification of plasmids by PCR-based replicon typing. J Microbiol Methods 63:219–228. https://doi.org/10.1016/j.mimet.2005.03.018. (PMID: 10.1016/j.mimet.2005.03.01815935499)
Chen J, Tian S, Nian H et al (2021) Carbapenem-resistant Enterobacter cloacae complex in a tertiary Hospital in Northeast China, 2010–2019. BMC Infect Dis 21:611. https://doi.org/10.1186/s12879-021-06250-0. (PMID: 10.1186/s12879-021-06250-0341748238235818)
CLSI (2021) Performance standards for antimicrobial susceptibility testing. 31st ed., The Clinical and Laboratory Standards Institute M100. Wayne, PA. https://clsi.org/standards/products/microbiology/documents/m100/ (Accessed 16 July 2023).
Das S (2023) The crisis of carbapenemase-mediated carbapenem resistance across the human-animal-environmental interface in India. Infect Dis Now 53:104628. https://doi.org/10.1016/j.idnow.2022.09.023. (PMID: 10.1016/j.idnow.2022.09.02336241158)
EUCAST (2021) Breakpoint tables for interpretation of MICs and zone diameters. version 11.0. The European Committee on Antimicrobial Susceptibility Testing. Vaxjo, Sweden. https://www.eucast.org/clinical_breakpoints . (Accessed 16 July 2023).
Garcia-Fernandez A, Fortini D, Veldman K et al (2009) Characterization of plasmids harbouring qnrS1, qnrB2 and qnrB19 genes in Salmonella. J Antimicrobial Chemother 63:274–281. https://doi.org/10.1093/jac/dkn470. (PMID: 10.1093/jac/dkn470)
Gopichand P, Agarwal G, Natarajan M et al (2019) In vitro effect of fosfomycin on multi-drug resistant gram-negative bacteria causing urinary tract infections. Infect Drug Resist 12:2005–2013. https://doi.org/10.2147/IDR.S207569. (PMID: 10.2147/IDR.S207569313720086628599)
Han R, Shi Q, Wu S et al (2020) Dissemination of carbapenemases (KPC, NDM, OXA-48, IMP, and VIM) among carbapenem-resistant Enterobacteriaceae isolated from adult and children patients in China. Front Cell Infect Microbiol 10:314. https://doi.org/10.3389/fcimb.2020.00314. (PMID: 10.3389/fcimb.2020.00314327197517347961)
Heras J, Dominguez C, Mata E et al (2015) GelJ- a tool for analyzing DNA fingerprint gel images. BMC Bioinformatics 16:270. https://doi.org/10.1186/s12859-015-0703-0. (PMID: 10.1186/s12859-015-0703-0263073534549892)
ICMR (2022) Antimicrobial resistance research and surveillance network. Annual report, January 2021 to December 2021. The Indian Council of Medical Research, India. https://main.icmr.nic.in/sites/default/files/upload_documents/AMR_Annual_Report_2021.pdf . (Accessed 16 July 2023).
Intra J, Carcione D, Sala RM et al (2023) Antimicrobial resistance patterns of Enterobacter cloacae and Klebsiella aerogenes strains isolated from clinical specimens: a twenty-year surveillance study. Antibiotics 12:775. https://doi.org/10.3390/antibiotics12040775. (PMID: 10.3390/antibiotics120407753710713710135309)
Johnson TJ, Bielak EM, Fortini D et al (2012) Expansion of the IncX plasmid family for improved identification and typing of novel plasmids in drug-resistant Enterobacteriaceae. Plasmid 68:43–50. https://doi.org/10.1016/j.plasmid.2012.03.001. (PMID: 10.1016/j.plasmid.2012.03.00122470007)
Kado CI, Liu ST (1981) Rapid procedure for detection and isolation of large and small plasmids. J Bact 145:1365–1373. https://doi.org/10.1128/jb.145.3.1365-1373.1981. (PMID: 10.1128/jb.145.3.1365-1373.19817009583217141)
Kananizadeh P, Oshiro S, Watanabe S et al (2020) Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring bla IMP-1 and mcr-9 in Japan. BMC Infect Dis 20:282. https://doi.org/10.1186/s12879-020-05021-7. (PMID: 10.1186/s12879-020-05021-7322993787161257)
Khajuria A, Praharaj AK, Kumar M et al (2014) Carbapenem resistance among Enterobacter species in a tertiary care hospital in central India. Chemother Res Pract 2014:972646. https://doi.org/10.1155/2014/972646. (PMID: 10.1155/2014/972646251800954142386)
Kopotsa K, Sekyere JO, Mbelle NM (2019) Plasmid evolution in carbapenemase-producing Enterobacteriaceae: a review. Ann N Y Acad Sci 1457:61–91. https://doi.org/10.1111/nyas.14223. (PMID: 10.1111/nyas.1422331469443)
Lee JJ, Lee JH, Kwon DB et al (2015) Fast and accurate large-scale detection of ß-lactamase genes conferring antibiotic resistance. Antimicrob Agents Chemother 59:5967–5975. https://doi.org/10.1128/AAC.04634-14. (PMID: 10.1128/AAC.04634-14261694154576124)
Liu J, Li GM, Lin LY et al (2016) Association of antibiotic resistance with SHV-12 extended-spectrum β-lactamase in Enterobacter cloacae. Exp Ther Med 11:269–276. https://doi.org/10.3892/etm.2015.2851. (PMID: 10.3892/etm.2015.285126889253)
Liu S, Huang N, Zhou C et al (2021) Molecular mechanisms and epidemiology of carbapenem-resistant Enterobacter cloacae complex Isolated from Chinese patients during 2004–2018. Infect Drug Resist 14:3647–3658. https://doi.org/10.2147/IDR.S327595. (PMID: 10.2147/IDR.S327595345221078434891)
Mallick A, Roy A, Sarkar S et al (2023) Customized molecular diagnostics of bacterial bloodstream infections for carbapenem resistance: a convenient and affordable approach. Pathog Glob Health 17:1–8. https://doi.org/10.1080/20477724.2023.2201982. (PMID: 10.1080/20477724.2023.2201982)
Manandhar S, Nguyen Q, Nguyen T et al (2022) Genomic epidemiology, antimicrobial resistance and virulence factors of Enterobacter cloacae complex causing potential community-onset bloodstream infections in a tertiary care hospital of Nepal. JAC Antimicrob Resist 4:dlac050. https://doi.org/10.1093/jacamr/dlac050. (PMID: 10.1093/jacamr/dlac050356638289155248)
Merhi G, Amayri S, Bitar I et al (2022) Whole genome-based characterization of multi-drug resistant Enterobacter and Klebsiella aerogenes isolates from Lebanon. Microbiol Spectrum 11:e02917-e2922. https://doi.org/10.1128/spectrum.02917-22. (PMID: 10.1128/spectrum.02917-22)
Mogasale VV, Saldanha P, Pai V et al (2021) A descriptive analysis of antimicrobial resistance patterns of WHO priority pathogens isolated in children from a tertiary care hospital in India. Sci Rep 11:5116. https://doi.org/10.1038/s41598-021-84293-8. (PMID: 10.1038/s41598-021-84293-8336643077933406)
Oshiro S, Tada T, Watanabe S et al (2020) Emergence and spread of carbapenemresistant and aminoglycoside-panresistant Enterobacter cloacae complex isolates coproducing NDM-type metallo-β-lactamase and 16S rRNA methylase in Myanmar. mSphere 5:e00054-20. https://doi.org/10.1128/mSphere.00054-20. (PMID: 10.1128/mSphere.00054-20321611447067590)
Ramirez MS, Iriarte A, Reyes-Lamothe R et al (2019) Small Klebsiella pneumoniae plasmids: neglected contributors to antibiotic resistance. Front Microbiol 10:2182. https://doi.org/10.3389/fmicb.2019.02182. (PMID: 10.3389/fmicb.2019.02182316163986764390)
Sumbana J, Santona A, Fiamma M et al (2022) Polyclonal emergence of MDR Enterobacter cloacae complex isolates producing multiple extended spectrum beta-lactamases at Maputo Central Hospital, Mozambique. Rend Fis Acc Lincei 33:39–45. https://doi.org/10.1007/s12210-021-01039-4. (PMID: 10.1007/s12210-021-01039-4)
Tilahun M, Kassa Y, Gedefie A et al (2021) Emerging carbapenem-resistant Enterobacteriaceae infection, its epidemiology and novel treatment options: a review. Infect Drug Resist 14:4363–4374. https://doi.org/10.2147/IDR.S337611. (PMID: 10.2147/IDR.S337611347073808544126)
Trevino M, Moldes L, Martinez-Lamas L et al (2009) Carbapenem-resistant Enterobacter cloacae and the emergence of metallo-beta-lactamase-producing strains in a third-level hospital (Santiago de Compostela, NW Spain). Eur J Clin Microbiol Infect Dis 28:1253–1258. https://doi.org/10.1007/s10096-009-0765-x. (PMID: 10.1007/s10096-009-0765-x19504135)
Villa L, Garcia-Fernandez A, Fortini D et al (2010) Replicon sequence typing of IncF plasmids carrying virulence and resistance determinants. J Antimicrob Chemother 65:2518–2529. https://doi.org/10.1093/jac/dkq347. (PMID: 10.1093/jac/dkq34720935300)
Wu C, Lin C, Zhu X et al (2018) The β-lactamase gene profile and a plasmid-carrying multiple heavy metal resistance genes of Enterobacter cloacae. Int J Genomics 2018:4989602. https://doi.org/10.1155/2018/4989602. (PMID: 10.1155/2018/4989602306714416317114)
Zhu Y, Jia X, Jia P et al (2021) Genetic and phenotypic characterization of the novel metallo-β-lactamase NDM-29 from Escherichia coli. Front Microbiol 12:743981. https://doi.org/10.3389/fmicb.2021.743981. (PMID: 10.3389/fmicb.2021.743981346591788511706)

AMR/Adhoc/241/2020-ECD-II Indian Council of Medical Research

Keywords: Enterobacter cloacae complex; Carbapenem resistance; Clone; Epidemiology; Plasmid; β-lactamases

EC 3.5.2.6 (beta-Lactamases)
0 (Anti-Bacterial Agents)
0 (Carbapenems)
0 (Bacterial Proteins)

Date Created: 20231120 Date Completed: 20240805 Latest Revision: 20240805

20240805

10.1007/s10123-023-00451-0

37985632