Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 58, Issue 12, Pages 7347-7357Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.03900-14
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Funding
- World Health Organization (WHO)
- National Institute for Health Research (NIHR) under Oxford Biomedical Research Centre Infection Theme
- United Kingdom Clinical Research Collaboration (UKCRC) Modernising Medical Microbiology Consortium
- UKCRC Translational Infection Research Initiative through grants from the Medical Research Council
- Biotechnology and Biological Sciences Research Council
- NIHR on behalf of the Department of Health [G0800778]
- Wellcome Trust [087646/Z/08/Z]
- Wellcome-Trust
- Wellcome Trust
- Royal Society [101237/Z/13/Z]
- NIHR
- MRC [G0800778, MR/K010174/1] Funding Source: UKRI
- Medical Research Council [G0800778, MR/K010174/1, MR/K010174/1B] Funding Source: researchfish
- National Institute for Health Research [HPRU-2012-10080, NF-SI-0512-10047, NF-SI-0508-10279] Funding Source: researchfish
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NDM-producing Klebsiella pneumoniae strains represent major clinical and infection control challenges, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid, or bacterial strain level and within hospital and/or the community has implications for monitoring and controlling spread. Whole-genome sequencing (WGS) is the highest-resolution typing method available for transmission epidemiology. We sequenced carbapenem-resistant K. pneumoniae isolates from 26 individuals involved in several infection case clusters in a Nepali neonatal unit and 68 other clinical Gram-negative isolates from a similar time frame, using Illumina and PacBio technologies. Within-outbreak chromosomal and closed-plasmid structures were generated and used as data set-specific references. Three temporally separated case clusters were caused by a single NDM K. pneumoniae strain with a conserved set of four plasmids, one being a 304,526-bp plasmid carrying blaNDM-1. The plasmids contained a large number of antimicrobial/heavy metal resistance and plasmid maintenance genes, which may have explained their persistence. No obvious environmental/human reservoir was found. There was no evidence of transmission of outbreak plasmids to other Gram-negative clinical isolates, although bla(NDM) variants were present in other isolates in different genetic contexts. WGS can effectively define complex antimicrobial resistance epidemiology. Wider sampling frames are required to contextualize outbreaks. Infection control may be effective in terminating outbreaks caused by particular strains, even in areas with widespread resistance, although this study could not demonstrate evidence supporting specific interventions. Larger, detailed studies are needed to characterize resistance genes, vectors, and host strains involved in disease, to enable effective intervention.
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