What is it about?
We applied multiple genomic technologies to help inform infection control responses to a superbug outbreak at a Brisbane hospital. The cause of the outbreak was a type of multidrug resistant bacteria known as CPE that is resistant to most commonly prescribed antibiotics. CPE do not usually cause problems for healthy people, but for critically-ill patients an infection with CPE can leave doctors with very limited options for treatment. This article shares our experience over three years characterising and monitoring the outbreak using a range of genomic approaches.
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Why is it important?
In 2015, integrating bacterial genomics during a hospital outbreak was still a rarity. As a microbial genomics group we were familiar with applying the latest DNA sequencing technologies to examine how bacteria evolved and caused disease, but we had relatively little experience in applying this knowledge in the clinic. In fact, this was our first attempt to communicate genomic analyses to clinical colleagues while an outbreak was still in progress. Our paper offers a candid account of this process from first recognition of the outbreak in 2015 to identification of a suspected source within the hospital plumbing nearly three years later. During the outbreak we integrated multiple genomic approaches (using Illumina, PacBio and Nanopore technologies) to address clinical questions and challenges as they arose. These included: -linking new CPE patient isolates to an historical isolate from the same ward two years prior, confirming a hospital source for the outbreak; -identifying the context of drug resistance genes on a broad-host range plasmid using PacBio long-read sequencing; -discovering the same plasmid is carried by unrelated bacteria from different hospitals in Queensland (and some other parts of Australia and Asia); -ruling out transmission of the original outbreak strain to a patient in a different ward using a rapid Nanopore sequencing; -identifying the original outbreak strain in water samples using metagenomics, implicating the hospital plumbing as an unexpected reservoir. Some of these methods are now considered routine. On the other hand, integrating these technologies altogether in a single outbreak investigation is uncommon. Ultimately we hope that presenting the entire investigation together with a ‘warts-and-all’ account of our experience integrating each genomic approach will be of general interest to anyone now implementing genomics in the clinical setting.
Perspectives
At the heart of our story is the transformation of bacterial genomics from an academic pursuit to a powerful investigative tool for the healthcare professional. Collaborations between our microbial genomics group at The University of Queensland (UQ) and Professor David Paterson’s clinical microbiology group at the UQ Centre for Clinical Research provided the means to translate our basic knowledge of genome sequencing and analysis direct to healthcare professionals. First author Dr Leah Roberts carried out much of this work as a PhD student, often working alongside her clinical counterpart, Dr Patrick Harris (UQCCR). Credit is due to Dr Roberts not just for driving the genomic analyses reported in our Nature Communications paper, but for her success in bridging the gap between basic genomic science and applied clinical science. Following the award of her PhD last year, this is a theme she now continues in her role as an EBPOD Post-doctoral Fellow at EMBL-EBI in Cambridge, United Kingdom. The interdisciplinary collaborations between clinical scientists, genome scientists, molecular microbiologists, and healthcare professionals that developed during our study proved vital in recent efforts to establish bacterial genomics in the Queensland healthcare system. With the aim of transitioning to a State-wide service in 2021, we are now piloting regular genomic reporting about multidrug resistant bacteria to Queensland hospitals. This State-funded Queensland Genomics project draws on many of our experiences first developed during the CPE outbreak reported here. Our paper outlines a number of scenarios where genomic reporting appeared to have the potential to positively impact patient outcomes (such as preventing onward transmission of the outbreak strain to other patients) or economic outcomes (such as avoiding unnecessary quarantine procedures). Speculation aside, this single study alone is insufficient to support evidence-based medicine in this area. There is an urgent need for more cross-disciplinary studies, including clinical trials and economic modelling, to measure the true impact of introducing bacterial genomics into the infection control workflow of healthcare facilities.
A/Prof Scott A Beatson
University of Queensland
Read the Original
This page is a summary of: Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei, Nature Communications, January 2020, Springer Science + Business Media,
DOI: 10.1038/s41467-019-14139-5.
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