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Volume 7, Issue 3

Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care Open Access

Abstract

Infections caused by carbapenem-resistant (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016–2018.

. and isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital.

In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since.

We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Acinetobacter baumannii , burns ward , carbapenem resistance , CR-Ab , genomics , intensive care unit , metagenomics , surveillance , WGS and whole-genome sequencing
Funding
This study was supported by the:
  • Australian Government Research Training Program
    • Principle Award Recipient: LeahWendy Roberts
  • Queensland Genomics
    • Principle Award Recipient: PatrickN. A. Harris
  • VC Strategic Initiative Funding UQ
    • Principle Award Recipient: PatrickN. A. Harris
  • National Health and Medical Research Council (Award GNT1106930)
    • Principle Award Recipient: MarkA. Schembri
  • National Health and Medical Research Council (Award GNT1157530)
    • Principle Award Recipient: PatrickN. A. Harris
  • National Health and Medical Research Council (Award GNT1090456)
    • Principle Award Recipient: ScottA. Beatson
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-02-18
2024-04-26
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References

  1. Otter JA, Burgess P, Davies F, Mookerjee S, Singleton J et al. Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae: an economic evaluation from a hospital perspective. Clin Microbiol Infect 2017; 23:188–196 [View Article][PubMed]
     [Google Scholar]
  2. Cruickshank MMC. Reducing Harm to Patients from Healthcare Associated Infections: an Australian Infection Prevention and Control Model for Acute Hospitals Sydney: Australian Commission on Safety and Quality in Health Care; 2009
     [Google Scholar]
  3. Gilchrist CA, Turner SD, Riley MF, Petri WA, Hewlett EL. Whole-genome sequencing in outbreak analysis. Clin Microbiol Rev 2015; 28:541–563 [View Article][PubMed]
     [Google Scholar]
  4. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21:538–582 [View Article][PubMed]
     [Google Scholar]
  5. Denton M, Wilcox MH, Parnell P, Green D, Keer V et al. Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit. J Hosp Infect 2004; 56:106–110 [View Article][PubMed]
     [Google Scholar]
  6. Doidge M, Allworth AM, Woods M, Marshall P, Terry M et al. Control of an outbreak of carbapenem-resistant Acinetobacter baumannii in Australia after introduction of environmental cleaning with a commercial oxidizing disinfectant. Infect Control Hosp Epidemiol 2010; 31:418–420 [View Article][PubMed]
     [Google Scholar]
  7. Wang SH, Sheng WH, Chang YY, Wang LH, Lin HC et al. ealthcare-associated outbreak due to pan-drug resistant Acinetobacter baumannii in a surgical intensive care unit. J Hosp Infect 2003; 53:97–102 [View Article][PubMed]
     [Google Scholar]
  8. Valencia R, Arroyo LA, Conde M, Aldana JM, Torres M-J et al. Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect Control Hosp Epidemiol 2009; 30:257–263 [View Article][PubMed]
     [Google Scholar]
  9. del Mar Tomas M, Cartelle M, Pertega S, Beceiro A, Llinares P et al. Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection. Clin Microbiol Infect 2005; 11:540–546 [View Article][PubMed]
     [Google Scholar]
  10. Nowak J, Zander E, Stefanik D, Higgins PG, Roca I et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 2017; 72:3277–3282 [View Article][PubMed]
     [Google Scholar]
  11. Xie R, Zhang XD, Zhao Q, Peng B, Zheng J. Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries. Emerg Microbes Infect 2018; 7:31 [View Article][PubMed]
     [Google Scholar]
  12. Jones CL, Clancy M, Honnold C, Singh S, Snesrud E et al. Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence. Clin Infect Dis 2015; 61:145–154 [View Article][PubMed]
     [Google Scholar]
  13. Kamolvit W, Sidjabat HE, Paterson DL. Molecular epidemiology and mechanisms of carbapenem resistance of Acinetobacter spp. in Asia and Oceania. Microb Drug Resist 2015; 21:424–434 [View Article][PubMed]
     [Google Scholar]
  14. Brown S, Amyes S. OXA (beta)-lactamases in Acinetobacter: the story so far. J Antimicrob Chemother 2006; 57:1–3 [View Article][PubMed]
     [Google Scholar]
  15. ACSQHC) ACoSaQiHC Aura 2019: third Australian report on antimicrobial use and resistance in human health. in. Sydney; 2019
  16. Roberts LW, Harris PNA, Forde BM, Ben Zakour NL, Catchpoole E et al. Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei . Nat Commun 2020; 11:466 [View Article][PubMed]
     [Google Scholar]
  17. Wood DE, Salzberg SL. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol 2014; 15:R46 [View Article][PubMed]
     [Google Scholar]
  18. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article][PubMed]
     [Google Scholar]
  19. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies. Bioinformatics 2013; 29:1072–1075 [View Article][PubMed]
     [Google Scholar]
  20. Seemann T. Snippy: fast bacterial variant calling from NGS reads; 2015
  21. Seemann T. mlst: https://github.com/tseemann/mlst. "This publication made use of the PubMLST website ( https://pubmlst.org/) developed by Keith Jolley (Jolley & Maiden 2010, BMC Bioinformatics, 11:595) and sited at the University of Oxford. The development of that website was funded by the Wellcome Trust".
  22. Bartual SG, Seifert H, Hippler C, Luzon MAD, Wisplinghoff H et al. Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii . J Clin Microbiol 2005; 43:4382–4390 [View Article][PubMed]
     [Google Scholar]
  23. Diancourt L, Passet V, Nemec A, Dijkshoorn L, Brisse S. The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS One 2010; 5:e10034 [View Article][PubMed]
     [Google Scholar]
  24. Seemann T. Abricate, Github https://github.com/tseemann/abricate .
  25. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article][PubMed]
     [Google Scholar]
  26. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article][PubMed]
     [Google Scholar]
  27. Sullivan MJ, Petty NK, Beatson SA. Easyfig: a genome comparison visualizer. Bioinformatics 2011; 27:1009–1010 [View Article][PubMed]
     [Google Scholar]
  28. Alikhan N-F, Petty NK, Ben Zakour NL, Beatson SA. blast ring image generator (BRIG): simple prokaryote genome comparisons. BMC Genomics 2011; 12:402 [View Article][PubMed]
     [Google Scholar]
  29. Rambaut A. FigTree; 2009
  30. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genom 2016; 2:e000102 [View Article][PubMed]
     [Google Scholar]
  31. Wyres KL, Cahill SM, Holt KE, Hall RM, Kenyon JJ. Identification of Acinetobacter baumannii loci for capsular polysaccharide (KL) and lipooligosaccharide outer core (OCL) synthesis in genome assemblies using curated reference databases compatible with Kaptive . Microb Genom 2020; 6: [View Article][PubMed]
     [Google Scholar]
  32. Inouye M, Dashnow H, Raven L-A, Schultz MB, Pope BJ et al. SRST2: rapid genomic surveillance for public health and hospital microbiology Labs. Genome Med 2014; 6:90 [View Article][PubMed]
     [Google Scholar]
  33. Gupta SK, Padmanabhan BR, Diene SM, Lopez-Rojas R, Kempf M et al. ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes. Antimicrob Agents Chemother 2014; 58:212–220 [View Article][PubMed]
     [Google Scholar]
  34. Ondov BD, Treangen TJ, Melsted P, Mallonee AB, Bergman NH et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol 2016; 17:132 [View Article][PubMed]
     [Google Scholar]
  35. Carver TJ, Rutherford KM, Berriman M, Rajandream MA, Barrell BG. Parkhill J: ACT: the Artemis Comparison Tool. Bioinformatics 2005; 21:3422–3423
     [Google Scholar]
  36. Whiteley CG, Lee D-J. Bacterial diguanylate cyclases: structure, function and mechanism in exopolysaccharide biofilm development. Biotechnol Adv 2015; 33:124–141 [View Article][PubMed]
     [Google Scholar]
  37. Corvec S, Caroff N, Espaze E, Giraudeau C, Drugeon H et al. AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains. J Antimicrob Chemother 2003; 52:629–635 [View Article][PubMed]
     [Google Scholar]
  38. Tomaras AP, Dorsey CW, Edelmann RE, Actis LA. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 2003; 149:3473–3484 [View Article][PubMed]
     [Google Scholar]
  39. Quainoo S, Coolen JPM, van Hijum SAFT, Huynen MA, Melchers WJG et al. Whole-genome sequencing of bacterial pathogens: the future of nosocomial outbreak analysis. Clin Microbiol Rev 2017; 30:1015–1063 [View Article][PubMed]
     [Google Scholar]
  40. Kwong JC, Lane CR, Romanes F, Gonçalves da Silva A, Easton M et al. Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak. PeerJ 2018; 6:e4210 [View Article][PubMed]
     [Google Scholar]
  41. Jiang Y, Resch S, Liu X, Rogers SO, Askari R et al. The cost of responding to an Acinetobacter outbreak in critically ill surgical patients. Surg Infect 2016; 17:58–64 [View Article][PubMed]
     [Google Scholar]
  42. Sadique Z, Lopman B, Cooper BS, Edmunds WJ. Cost-effectiveness of ward closure to control outbreaks of norovirus infection in United Kingdom National health service hospitals. J Infect Dis 2016; 213 Suppl 1:S19–26 [View Article][PubMed]
     [Google Scholar]
  43. Rodriguez-Acevedo AJ, Lee XJ, Elliott TM, Gordon LG. Hospitalization costs for patients colonized with carbapenemase-producing Enterobacterales during an Australian outbreak. J Hosp Infect 2020; 105:146–153 [View Article][PubMed]
     [Google Scholar]
  44. Argimón S, Masim MAL, Gayeta JM, Lagrada ML, Macaranas PKV et al. Integrating whole-genome sequencing within the National Antimicrobial Resistance Surveillance Program in the Philippines. Nat Commun 2020; 11:2719 [View Article][PubMed]
     [Google Scholar]
  45. Harris SR, Feil EJ, Holden MTG, Quail MA, Nickerson EK et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 2010; 327:469–474 [View Article][PubMed]
     [Google Scholar]
  46. Schürch AC, Arredondo-Alonso S, Willems RJL, Goering RV. Whole genome sequencing options for bacterial strain typing and epidemiologic analysis based on single nucleotide polymorphism versus gene-by-gene-based approaches. Clin Microbiol Infect 2018; 24:350–354 [View Article][PubMed]
     [Google Scholar]
  47. Peacock SJ, Parkhill J, Brown NM. Changing the paradigm for hospital outbreak detection by leading with genomic surveillance of nosocomial pathogens. Microbiology 2018; 164:1213–1219 [View Article][PubMed]
     [Google Scholar]
  48. Stimson J, Gardy J, Mathema B, Crudu V, Cohen T et al. Beyond the SNP threshold:identifying outbreak clusters using inferred transmissions. Mol Biol Evol 2019; 36:587–603 [View Article][PubMed]
     [Google Scholar]
  49. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis 2006; 6:130 [View Article][PubMed]
     [Google Scholar]
  50. Sugawara E, Nikaido H. Ompa is the principal nonspecific slow porin of Acinetobacter baumannii . J Bacteriol 2012; 194:4089–4096 [View Article][PubMed]
     [Google Scholar]
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Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care
M Gen 7, 000530 (2021); https://doi.org/10.1099/mgen.0.000530
/content/journal/mgen/10.1099/mgen.0.000530
/content/journal/mgen/10.1099/mgen.0.000530
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