Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens

Forde, Brian; Bergh, Haakon; Cuddihy, Thom; Hajkowicz, Krispin; Hurst, Trish; Playford, E Geoffrey; Henderson, Belinda; Runnegar, Naomi; Clark, Julia; Jennison, Amy V.; Moss, Susan; Hume, Anna; Leroux, Hugo; Beatson, Scott A.; Paterson, David L.; Harris, Patrick N A

doi:10.1093/cid/ciac726

Cited by 34 publications

(26 citation statements)

References 23 publications

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“…In a whole-genome sequencing (WGS)-based surveillance study conducted in three hospitals in Brisbane, Queensland, 293 CPE isolates were sequenced. 34 In line with CARAlert data, bla IMP-4 (n = 170) was the most common type of carbapenemase, followed by bla NDM (n = 39) and bla OXA-48-like (n = 21). Seven isolates had NDM and OXA-48-like carbapenemases concurrently and bla KPC-2 was identified in only five isolates.…”

Section: Current Status Of Carbapenemases In Australiasupporting

confidence: 64%

Epidemiology and clinical significance of carbapenemases in Australia: a narrative review

Aslan,

Paterson

2024

Internal Medicine Journal

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Carbapenemase‐producing gram‐negative bacteria (CP‐GNB) infections threaten public health with high mortality, morbidity and treatment costs. Although frequencies remain low in Australia (total number of CP‐GNB infections reported was 907 in 2022), blaIMP‐4 has established low levels of endemicity in many states. Imipenemase metallo‐β‐lactamase types alone accounted for more than half of all carbapenemases in carbapenemase‐producing Enterobacterales isolates in Australia, particularly in Enterobacter cloacae complex. New Delhi metallo‐β‐lactamase constitutes almost 25% of all carbapenemases in Australia and was identified predominantly in Escherichia coli. The OXA‐48‐like carbapenemases include almost 10% of all carbapenemases and are mainly seen in Klebsiella pneumoniae and E. coli. Although K. pneumoniae carbapenemase‐type carbapenemases are rare in Australia, some local outbreaks have occurred. Most carbapenem‐resistant (CR) Pseudomonas aeruginosa strains in Australia do not produce carbapenemases. Finally, OXA‐23‐like carbapenemases are overwhelmingly positive in CR‐Acinetobacter baumannii strains in Australia. Treatment of CR‐GNB infections challenges physicians. Of 10 new antibiotics active against at least some CR‐GNB infections that are approved by the US Food and Drug Administration, just three are approved for use in Australia. In this context, there is still an unmet need for novel antibacterials that can be used for the treatment of CR‐GNB infections in Australia, as well as a pressing requirement for new mechanisms to ‘de‐link’ antibiotic sales from their availability. In this narrative review, we aim to overview the epidemiology and clinical significance of carbapenem resistance in Australia as it pertains to Enterobacterales, P. aeruginosa and A. baumannii.

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Section: Current Status Of Carbapenemases In Australiasupporting

confidence: 64%

Epidemiology and clinical significance of carbapenemases in Australia: a narrative review

Aslan,

Paterson

2024

Internal Medicine Journal

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“…Our findings suggest that sequence-based surveillance of VREfm screening samples would be useful in identifying outbreaks proactively. A proactive approach would avoid large outbreaks of infection, reduce costs of ward closure and the clinical impact of invasive disease (48–51). In our setting an outbreak of VREfm was suspected 3 weeks after the study collection period when P9 and P49 developed bloodstream infection concurrently but this was many weeks after VREfm transmission had likely occurred (Figure 1 and Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin resistantEnterococcus faecium

McHugh

Pettigrew

Taori

et al. 2022

Preprint

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Whole genome sequencing is increasingly applied to healthcare-associated vancomycin resistant Enterococcus faecium (VREfm) outbreak investigations using single bacterial colonies from individual patients. However, within-patient diversity could complicate transmission resolution. We sequenced 14 colonies from VREfm positive rectal swabs over a 1-month period on a haematology unit. In total, 224 isolates from 11 patients were sequenced. Carriage of 2-3 sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within isolates from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies, and therefore there is a need to capture and consider VREfm within-patient diversity to ensure accurate resolution of transmission networks.

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“…One study documented cryptic transmission of new MDR-E lineage using weekly perirectal swab surveillance cultures [59]. In another study, routine WGS on bacterial culture isolates ( Staphylococcus aureus , enterococci, Acinetobacter baumannii , Enterobacterales) from hospitalized patients could identify the interhospital spread of drug resistance genes, as well as the sequence types that arose in the community [61]. Detailed transmission information could then help inform infection control measures and the need for continued surveillance.…”

Section: Whole Genome Sequencingmentioning

confidence: 99%

Sequence-based diagnostics and precision medicine in bacterial and viral infections: from bench to bedside

Pham

Hanson

et al. 2023

Current Opinion in Infectious Diseases

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Purpose of review Nucleic acid sequence-based organism identification plays an important role in the diagnosis and management of transplant and cancer-associated infectious diseases. Here, we provide a high-level overview of advanced sequencing technologies, discuss test performance, and highlight unmet research needs with a focus on immunocompromised hosts. Recent findings Next-generation sequencing (NGS) technologies are powerful tools with a growing role in managing immunocompromised patients with suspected infection. Targeted NGS (tNGS) can identify pathogens directly from patient specimens, especially for mixed samples, and has been used to detect resistance mutations in transplant-related viruses (e.g. CMV). Whole-genome sequencing (WGS) is increasingly used for outbreak investigations and infection control. Metagenomic NGS (mNGS) is useful for hypothesis-free testing and can simultaneously assess pathogens and host response to infection. Summary NGS testing increases diagnostic yield relative to standard culture and Sanger sequencing but may be limited by high cost, turnaround times, and detection of unexpected organisms or commensals of uncertain significance. Close collaboration with the clinical microbiology laboratory and infectious diseases is recommended when NGS testing is considered. Additional research is required to understand which immunocompromised patients are most likely to benefit from NGS testing, and when testing should ideally be performed.

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Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens

Cited by 34 publications

References 23 publications

Epidemiology and clinical significance of carbapenemases in Australia: a narrative review

Epidemiology and clinical significance of carbapenemases in Australia: a narrative review

Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin resistantEnterococcus faecium

Sequence-based diagnostics and precision medicine in bacterial and viral infections: from bench to bedside

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