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      Extensive outbreak of colistin resistant, carbapenemase ( bla OXA-48, bla NDM) producing Klebsiella pneumoniae in a large tertiary care hospital, India

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          Abstract

          Background

          Extensive drug resistance in Klebsiella pneumoniae ( K. pneumoniae) causing major outbreaks in large hospitals is an emerging challenge. We describe a near fatal outbreak of colistin resistant, carbapenem resistant K. pneumoniae (CRKp) producing metallo beta-lactamases ( bla NDM) and bla OXA-48 in the neonatal intensive care unit (NICU) at the background of a larger outbreak involving multiple parts of the hospital and the challenges in its containment.

          Methods

          Following identification of an outbreak due to colistin resistant CRKp between April to June 2017 in the NICU, a thorough surveillance of similar cases and the hospital environment was performed to trace the source. All the isolated K. pneumoniae were tested for susceptibility to standard antibiotics by disc diffusion and microbroth dilution methods. Molecular detection of extended spectrum beta lactamases (ESBLs) and carbapenemases (classes A, B, D) genes was done. Enterobacterial repetitive intergenic consensus (ERIC) PCR and multi-locus sequence typing (MLST) was done to determine the genetic relatedness of the isolates. Characteristics of different sequence types were statistically compared (Student’s t-test).

          Results

          A total of 45 K . pneumoniae isolates were studied from NICU (14 cases of neonatal sepsis), ICU (18 cases), other wards (7 cases) along with 6 isolates from hospital environment and human colonizers. The primary case was identified in the ICU. All the K. pneumoniae from NICU and 94.4% from the ICU were colistin resistant CRKp. Majority (59.37% and 56.25%) harbored bla SHV/ bla CTXM and bla OXA-48 genes, respectively. Two distinct sequence types ST5235 and ST5313 were noted with colistin resistance, distribution within the NICU and mortality as significant attributes of ST5235 ( p < 0.05). The outbreak was contained with strengthening of the infection control practices and unintended short duration closure of the hospital.

          Conclusion

          Large hospital outbreaks with considerable mortality can be caused by non-dominant clones of colistin resistant CRKp harboring bla OXA-48 and bla NDM carbapenemases in endemic regions. The exact global impact of these sequence types should be further studied to prevent future fatal outbreaks.

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          Most cited references26

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          Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes.

          Dispersed repetitive DNA sequences have been described recently in eubacteria. To assess the distribution and evolutionary conservation of two distinct prokaryotic repetitive elements, consensus oligonucleotides were used in polymerase chain reaction [PCR] amplification and slot blot hybridization experiments with genomic DNA from diverse eubacterial species. Oligonucleotides matching Repetitive Extragenic Palindromic [REP] elements and Enterobacterial Repetitive Intergenic Consensus [ERIC] sequences were synthesized and tested as opposing PCR primers in the amplification of eubacterial genomic DNA. REP and ERIC consensus oligonucleotides produced clearly resolvable bands by agarose gel electrophoresis following PCR amplification. These band patterns provided unambiguous DNA fingerprints of different eubacterial species and strains. Both REP and ERIC probes hybridized preferentially to genomic DNA from Gram-negative enteric bacteria and related species. Widespread distribution of these repetitive DNA elements in the genomes of various microorganisms should enable rapid identification of bacterial species and strains, and be useful for the analysis of prokaryotic genomes.
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            Multiplex PCR for detection of acquired carbapenemase genes.

            A rapid and reliable PCR-based technique was developed for detection of genes encoding carbapenemases belonging to different classes. Primers were designed to amplify the following 11 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). Three different multiplex reaction mixtures were defined and evaluated for the detection of all these 11 genes. Using optimized conditions, each reaction mixture allowed to identify the respective genes, with PCR giving distinct amplicon sizes corresponding to the different genes for each mixture. We reported here a rapid and reliable technique for screening all clinically relevant carbapenemase genes. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates.

              A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.
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                Author and article information

                Contributors
                swati.sharma@bhu.ac.in
                drtuhina@yahoo.com
                ashokkumar_bhu@hotmail.com
                ghanshyambhu1976@gmail.com
                sriparna.neonat@aiimsrishikesh.edu.in
                Journal
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                2047-2994
                6 January 2022
                6 January 2022
                2022
                : 11
                : 1
                Affiliations
                [1 ]GRID grid.411507.6, ISNI 0000 0001 2287 8816, Department of Microbiology, Institute of Medical Sciences, , Banaras Hindu University, ; Varanasi, 221005 India
                [2 ]GRID grid.411507.6, ISNI 0000 0001 2287 8816, Department of Pediatrics, Institute of Medical Sciences, , Banaras Hindu University, ; Varanasi, India
                [3 ]GRID grid.411507.6, ISNI 0000 0001 2287 8816, Department of Anaesthesiology, Institute of Medical Sciences, , Banaras Hindu University, ; Varanasi, India
                [4 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Neonatology, , All India Institute of Medical Sciences, ; Rishikesh, India
                Author information
                http://orcid.org/0000-0003-0035-2842
                Article
                1048
                10.1186/s13756-021-01048-w
                8740481
                34991724
                cb5a7c72-9f9b-4e44-8da9-cb2b3827c555
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 July 2021
                : 26 December 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Infectious disease & Microbiology
                blaoxa-48,crkp,fatal,hospital environment,st5235,st5313,surveillance
                Infectious disease & Microbiology
                blaoxa-48, crkp, fatal, hospital environment, st5235, st5313, surveillance

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