Whole-Genome Sequencing for Investigating a Health Care-Associated Outbreak of Carbapenem-Resistant Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in hospital settings challenge the treatment of patients and infection control. Understanding the relatedness of clinical isolates is important in distinguishing outbreak isolates from sporadic cases. This study investigated 11 CRAB isolates from a hospital outbreak by whole-genome sequencing (WGS), utilizing various bioinformatics tools for outbreak analysis. The results of multilocus sequence typing (MLST), single nucleotide polymorphism (SNP) analysis, and phylogenetic tree analysis by WGS through web-based tools were compared, and repetitive element polymerase chain reaction (rep-PCR) typing was performed. Through the WGS of 11 A. baumannii isolates, three clonal lineages were identified from the outbreak. The coexistence of blaOXA-23, blaOXA-66, blaADC-25, and armA with additional aminoglycoside-inactivating enzymes, predicted to confer multidrug resistance, was identified in all isolates. The MLST Oxford scheme identified three types (ST191, ST369, and ST451), and, through whole-genome MLST and whole-genome SNP analyses, different clones were found to exist within the MLST types. wgSNP showed the highest discriminatory power with the lowest similarities among the isolates. Using the various bioinformatics tools for WGS, CRAB outbreak analysis was applicable and identified three discrete clusters differentiating the separate epidemiologic relationships among the isolates.

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Faculty Opinions recommendation of Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717957002.793461477 ◽

2012 ◽

Author(s):

Mark Ragan ◽

Cheong Xin Chan

Keyword(s):

Klebsiella Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Hospital Outbreak ◽

Carbapenem Resistant

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2461. Community-Acquired in Name Only: A Cluster of Carbapenem-Resistant Acinetobacter baumannii in a Burn Intensive Care Unit

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2139 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S852-S852

Author(s):

Erica S Shenoy ◽

Virginia M Pierce ◽

Mohamad Sater ◽

Febriana Pangestu ◽

Ian Herriott ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

Carbapenem Resistance ◽

Environmental Sampling ◽

Whole Genome ◽

Single Source ◽

Carbapenem Resistant

Abstract Background Detection of nosocomial outbreaks often relies on epidemiological definitions of community and nosocomial acquisition. We report a cluster of three carbapenem-resistant Acinetobacter baumannii (CRAB) infections linked to a single source patient with infections occurring within 2 days of admission to a burn intensive care unit (ICU). The epidemiological investigation was supplemented by whole-genome sequencing (WGS) of clinical and environmental isolates. Methods Study participants included burn ICU patients identified with infections caused by CRAB. A detailed review of patient demographic and clinical data was conducted. Clinical A. baumannii isolates were assessed by antimicrobial susceptibility testing and WGS. Review of infection control practices on the affected unit was followed by environmental sampling. A. baumannii isolates obtained through environmental sampling were assessed for carbapenem resistance and then underwent WGS for comparison to the clinical isolates. Results Three cases of CRAB infection in the affected unit spanning a period of 3 months were linked to a preceding source patient, with CRAB isolates from the four patients differing by 5–7 single nucleotide variations. All case patients had been admitted to the same room within 2 days before development of CRAB infection. Environmental sampling performed while the third case patient occupied the room identified highly contaminated areas, and environmental CRAB isolates linked the patient isolates. The contaminated areas were subsequently re-sampled after enhanced terminal cleaning of the room. No additional CRAB was isolated, but other pathogenic organisms were recovered. Conclusion We report a cluster of three infections caused by highly resistant A. baumannii that occurred in a burn intensive care unit over a period of 3 months, linked to a single source patient. Three case patients developed infections classified as community-acquired using standard epidemiological definitions, however, whole-genome sequencing revealed clonality. An extensive investigation identified the role of environmental reservoirs. Burn patients may be particularly vulnerable to early-onset nosocomial infection from environmental contamination. Disclosures All authors: No reported disclosures.

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mSphere of Influence: Whole-Genome Sequencing, a Vital Tool for the Interruption of Nosocomial Transmission

mSphere ◽

10.1128/msphere.00230-21 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Ahmed Babiker

Keyword(s):

Health Care ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Nosocomial Transmission ◽

Whole Genome ◽

Content Type ◽

Genomic Epidemiology ◽

Hospital Outbreak ◽

Carbapenem Resistant

ABSTRACT Ahmed Babiker’s work focuses on the clinical and genomic epidemiology of multidrug-resistant health care-associated pathogens and other high-consequence pathogens. In this mSphere of Influence article, he reflects on how the paper “Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing” by Evan S. Snitkin et al. (Sci Transl Med 4:148ra116, 2012, https://doi.org/10.1126/scitranslmed.3004129) impacted his thinking on the use of whole-genome sequencing for nosocomial transmission investigation.

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Molecular dissection of Carbapenem-resistant Acinetobacter baumannii circulating in Indian hospitals using Whole Genome Sequencing

10.1101/2021.07.30.454432 ◽

2021 ◽

Author(s):

Steffimol Rose ◽

Varun Shamanna ◽

Anthony Underwood ◽

Geetha Nagaraj ◽

Akshatha Prasanna ◽

...

Keyword(s):

Molecular Epidemiology ◽

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

Clonal Complex ◽

Carbapenem Resistance ◽

Evolutionary Divergence ◽

Whole Genome ◽

Northern India ◽

Carbapenem Resistant

Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) has acquired worldwide recognition as a serious nosocomial infection. It poses a concern to hospitalized patients because of the limited therapeutic options available. Thus, we investigated the molecular epidemiology and antibiotic resistance profiles of A. baumannii isolates in India. Materials and Methods: We characterized 306 retrospective A. baumannii clinical isolates collected from 18 centers across 10 states and 1 Union Territory of India between 2015 and 2019. Molecular epidemiology, and carbapenem resistance were studied by Whole Genome Sequencing. Results: A total of 105 different Sequence Types (STs) were identified including 48 reported STs and 57 Novel STs. 99 isolates were classified into Clonal Complex 451 (CC451) among which ST848 and ST1956 were the common STs. Carbapenemase resistance was confirmed in all the isolates with the presence of intrinsic bla OXA -51-like genes, and the acquired bla OXA-23 and bla NDM-1 genes. Conclusion: Most of the isolates were grouped under clonal complex 451. ST1053 caused an outbreak in Northern India during 2018 and 2019. Novel MLST alleles and STs were also detected, underlining an evolutionary divergence in India. The carbapenem-resistance was dominated by OXA-type carbapenemases and further surveillance of these carbapenem-resistant A. baumannii and antimicrobial stewardship should be strengthened.

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Evolution of Carbapenem-Resistant Acinetobacter baumannii Revealed through Whole-Genome Sequencing and Comparative Genomic Analysis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04609-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1168-1176 ◽

Cited By ~ 23

Author(s):

Henan Li ◽

Fei Liu ◽

Yawei Zhang ◽

Xiaojuan Wang ◽

Chunjiang Zhao ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

Resistance Genes ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Comparative Genomic ◽

Whole Genome ◽

Content Type ◽

Carbapenem Resistant

ABSTRACTAcinetobacter baumanniiis a globally important nosocomial pathogen characterized by an evolving multidrug resistance. A total of 35 representative clinicalA. baumanniistrains isolated from 13 hospitals in nine cities in China from 1999 to 2011, including 32 carbapenem-resistant and 3 carbapenem-susceptibleA. baumanniistrains, were selected for whole-genome sequencing and comparative genomic analysis. Phylogenetic analysis revealed that the earliest strain, strain 1999BJAB11, and two strains isolated in Zhejiang Province in 2004 were the founder strains of carbapenem-resistantA. baumannii. Ten types of AbaR resistance islands were identified, and a previously unreported AbaR island, which comprised a two-component response regulator, resistance-related proteins, and RND efflux system proteins, was identified in two strains isolated in Zhejiang in 2004. Multiple transposons or insertion sequences (ISs) existed in each strain, and these gradually tended to diversify with evolution. Some of these IS elements or transposons were the first to be reported, and most of them were mainly found in strains from two provinces. Genome feature analysis illustrated diversified resistance genes, surface polysaccharides, and a restriction-modification system, even in strains that were phylogenetically and epidemiologically very closely related. IS-mediated deletions were identified in the type VI secretion system region, thecsuEregion, and core lipooligosaccharide (LOS) loci. Recombination occurred in the heme utilization region, and intrinsic resistance genes (blaADCandblaOXA-51-likevariants) and three novelblaOXA-51-likevariants (blaOXA-424,blaOXA-425, andblaOXA-426) were identified. Our results could improve the understanding of the evolutionary processes that contribute to the emergence of carbapenem-resistantA. baumanniistrains and help elucidate the molecular evolutionary mechanism inA. baumannii.

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High-throughput whole-genome sequencing to dissect the epidemiology of Acinetobacter baumannii isolates from a hospital outbreak

Journal of Hospital Infection ◽

10.1016/j.jhin.2010.01.012 ◽

2010 ◽

Vol 75 (1) ◽

pp. 37-41 ◽

Cited By ~ 102

Author(s):

T. Lewis ◽

N.J. Loman ◽

L. Bingle ◽

P. Jumaa ◽

G.M. Weinstock ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

High Throughput ◽

Whole Genome ◽

Hospital Outbreak

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Stalking a lethal superbug by whole-genome sequencing and phylogenetics: Influence on unraveling a major hospital outbreak of carbapenem-resistant Klebsiella pneumoniae

American Journal of Infection Control ◽

10.1016/j.ajic.2017.07.022 ◽

2018 ◽

Vol 46 (1) ◽

pp. 54-59 ◽

Cited By ~ 11

Author(s):

Thorsten Kaiser ◽

Knut Finstermeier ◽

Madlen Häntzsch ◽

Sarah Faucheux ◽

Martin Kaase ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Hospital Outbreak ◽

Carbapenem Resistant

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Whole genome sequencing of Clostridioides difficile PCR ribotype 046 suggests transmission between pigs and humans

PLoS ONE ◽

10.1371/journal.pone.0244227 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244227

Author(s):

Anders Werner ◽

Paula Mölling ◽

Anna Fagerström ◽

Fredrik Dyrkell ◽

Dimitrios Arnellos ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

General Pattern ◽

Snp Analysis ◽

Whole Genome ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Neonatal Pigs ◽

Hospital Outbreak ◽

Clostridioides Difficile

Background A zoonotic association has been suggested for several PCR ribotypes (RTs) of Clostridioides difficile. In central parts of Sweden, RT046 was found dominant in neonatal pigs at the same time as a RT046 hospital C. difficile infection (CDI) outbreak occurred in the southern parts of the country. Objective To detect possible transmission of RT046 between pig farms and human CDI cases in Sweden and investigate the diversity of RT046 in the pig population using whole genome sequencing (WGS). Methods WGS was performed on 47 C. difficile isolates from pigs (n = 22), the farm environment (n = 7) and human cases of CDI (n = 18). Two different core genome multilocus sequencing typing (cgMLST) schemes were used together with a single nucleotide polymorphisms (SNP) analysis and the results were related to time and location of isolation of the isolates. Results The pig isolates were closely related (≤6 cgMLST alleles differing in both cgMLST schemes) and conserved over time and were clearly separated from isolates from the human hospital outbreak (≥76 and ≥90 cgMLST alleles differing in the two cgMLST schemes). However, two human isolates were closely related to the pig isolates, suggesting possible transmission. The SNP analysis was not more discriminate than cgMLST. Conclusion No general pattern suggesting zoonotic transmission was apparent between pigs and humans, although contrasting results from two isolates still make transmission possible. Our results support the need for high resolution WGS typing when investigating hospital and environmental transmission of C. difficile.

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