Genome sequencing of an extended series of NDM-Klebsiella pneumoniae neonatal infections in a Nepali hospital characterizes the extent of community versus hospital-associated transmission in an endemic setting.

Stoesser, N., Giess, A., Batty, E.M., Sheppard, A.E., Walker, A.S., Wilson, D.J., Didelot, X., Bashir, A., Sebra, R., Kasarskis, A., Sthapit, B., Shakya, M., Kelly, D., Pollard, A.J., Peto, T.E., Crook, D.W., Donnelly, P., Thorson, S., Amatya, P. and S. Joshi (2014)
Antimicrobial Agents and Chemotherapy 58: 7347-7357. (pdf)

BACKGROUND: NDM-producing Klebsiella pneumoniae represent a major clinical and infection control challenge, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid or bacterial strain level, 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.

METHODS: 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 timeframe, using Illumina and PacBio technologies. Within-outbreak chromosomal and closed plasmid structures were generated, and used as dataset-specific references.

RESULTS: Three temporally separated case clusters were caused by a single NDM-K. pneumoniae strain, with a conserved set of four plasmids, one being a 304,526bp blaNDM-1-plasmid. The plasmids contained a large number of antimicrobial/heavy metal resistance and plasmid maintenance genes, which may have explained persistence. No obvious environmental/human reservoir was found. There was no evidence of transmission of outbreak plasmids to other Gram-negative clinical isolates, although blaNDM variants were present in other isolates in different genetic contexts.

CONCLUSIONS: 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.