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Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing.
Sci Transl Med. 2012 Aug 22; 4(148):148ra116
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27 Sep 2012
New Finding
DOI: 10.3410/f.717957002.793461477
This article describes the application of whole-genome sequencing to trace an outbreak of an emerging superbug in a hospital setting. Genome sequence and epidemiological data are integrated to yield remarkable insights into how a bacterial pathogen has been transmitted among patients, and how this transmission...Continue reading
This article describes the application of whole-genome sequencing to trace an outbreak of an emerging superbug in a hospital setting. Genome sequence and epidemiological data are integrated to yield remarkable insights into how a bacterial pathogen has been transmitted among patients, and how this transmission might be managed. This combined approach offers an example of how the spread of other infectious diseases might be controlled.
Using genome-wide single-nucleotide variant (SNV) profiles, the authors demonstrate that despite a three-week interval between the first and subsequent cases of carbapenem-resistant Klebsiella pneumoniae, the outbreak in question was, nonetheless, monoclonal. Combining the SNV profiles with epidemiological data and patient follow-up, they were able to show that the first patient transmitted the bacterium in three separate events, from two different sites on her body, yielding two main clusters of colonised patients. The authors link these transmissions to contaminated medical equipment and identify subsequent development of further antibiotic resistance (to colistin) in more-recent isolates.
These findings provide an essential reference for the management and containment of nosocomial infections based on whole-genome sequencing of isolated pathogens and demonstrate the potential of using serial, real-time sequencing as a surveillance tool for monitoring the spread of infections and informing how patients and/or hospital wards might best be managed.
Perhaps more importantly, the article also presents alarming evidence of how resilient K. pneumoniae can be to even the strictest (current best standard of practice) cleaning regimes for medical equipment, and how quickly superbugs can develop resistance to an ever-broader spectrum of antibiotics.
In short, this work demonstrates a remarkably powerful integration of genomic and epidemiological data to facilitate decision-making in managing nosocomial transmission in particular, and infectious disease more generally.
Using genome-wide single-nucleotide variant (SNV) profiles, the authors demonstrate that despite a three-week interval between the first and subsequent cases of carbapenem-resistant Klebsiella pneumoniae, the outbreak in question was, nonetheless, monoclonal. Combining the SNV profiles with epidemiological data and patient follow-up, they were able to show that the first patient transmitted the bacterium in three separate events, from two different sites on her body, yielding two main clusters of colonised patients. The authors link these transmissions to contaminated medical equipment and identify subsequent development of further antibiotic resistance (to colistin) in more-recent isolates.
These findings provide an essential reference for the management and containment of nosocomial infections based on whole-genome sequencing of isolated pathogens and demonstrate the potential of using serial, real-time sequencing as a surveillance tool for monitoring the spread of infections and informing how patients and/or hospital wards might best be managed.
Perhaps more importantly, the article also presents alarming evidence of how resilient K. pneumoniae can be to even the strictest (current best standard of practice) cleaning regimes for medical equipment, and how quickly superbugs can develop resistance to an ever-broader spectrum of antibiotics.
In short, this work demonstrates a remarkably powerful integration of genomic and epidemiological data to facilitate decision-making in managing nosocomial transmission in particular, and infectious disease more generally.
Disclosures
None declared
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Ragan M and Chan C: F1000Prime Recommendation of [Snitkin ES et al., Sci Transl Med 2012, 4(148):148ra116]. In F1000Prime, 27 Sep 2012; DOI: 10.3410/f.717957002.793461477. F1000Prime.com/717957002#eval793461477
F1000Prime Recommendations, Dissents and Comments for [Snitkin ES et al., Sci Transl Med 2012, 4(148):148ra116]. In F1000Prime, 23 May 2013; F1000Prime.com/717957002
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The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U.S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.
DOI: 10.1126/scitranslmed.3004129
PMID: 22914622
