Genomic surveillance, characterisation and intervention of a carbapenem-resistant Acinetobacter baumannii outbreak in critical care

Infections caused by carbapenem-resistant Acinetobacter baumannii (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 polymicrobial outbreak in a Brisbane hospital between 2016-2018. 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 and within 10 single nucleotide polymorphisms (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 K. pneumoniae 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. Here we demonstrate implementation of a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting. ### Competing Interest Statement PNAH has received research grants from MSD, Sandoz and Shionogi Ltd, outside of the submitted work, and speaker fees from Pfizer paid to The University of Queensland. DLP reports receiving grants and personal fees from Shionogi and Merck Sharp and Dohme and personal fees from Pfizer, Achaogen, AstraZeneca, Leo Pharmaceuticals, Bayer, GlaxoSmithKline, Cubist, Venatorx, and Accelerate. JL has received personal fees from Pfizer and MSD and grants from MSD paid to The University of Queensland. The other authors have no conflicts of interest to declare. ### Funding Statement LWR was supported by an Australian Government Research Training Program (RTP) Scholarship. SAB, PNAH and MAS were supported by fellowships from the Australian National Health and Medical Research Council (GNT1090456, GNT1157530 and GNT1106930, respectively). The work was supported by VC Strategic Intitiative Funding from The University of Queensland (2016-2018) and grants from the Queensland Genomics Health Alliance (now Queensland Genomics), Queensland Health, Queensland Government. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was provided by the RBWH HREC as a low-risk study with waiver of consent (HREC/16/QRBW/581). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets supporting the conclusions of this article are available in the short read archive (SRA) repository, under the following Bioprojects: the complete genomes for MS14413 (GenBank: [CP054302.1][1]) and MS14393 (GenBank: [CP054303][2]-[CP054305][3]) have been deposited under the Bioprojects PRJNA631347 and PRJNA631348, respectively. All isolate Illumina sequencing reads have been deposited under the Bioproject PRJNA631491. All metagenomic Illumina sequencing reads have been deposited under the Bioproject PRJNA631351. [1]: /lookup/external-ref?link_type=GEN&access_num=CP054302.1&atom=%2Fmedrxiv%2Fearly%2F2020%2F08%2F14%2F2020.08.10.20166652.atom [2]: /lookup/external-ref?link_type=GEN&access_num=CP054303&atom=%2Fmedrxiv%2Fearly%2F2020%2F08%2F14%2F2020.08.10.20166652.atom [3]: /lookup/external-ref?link_type=GEN&access_num=CP054305&atom=%2Fmedrxiv%2Fearly%2F2020%2F08%2F14%2F2020.08.10.20166652.atom