Genome Sequencing Identifies Previously Unrecognized Klebsiella pneumoniae Outbreaks in Neonatal Intensive Care Units in the Philippines

Carlos, C. C.; Masim, M. A. L.; Lagrada, M. L.; Gayeta, J. M.; Macaranas, P. K. V.; Sia, S. B.; Facun, M. A. M.; Palarca, J. F. C.; Olorosa, A. M.; Cueno, G. A. C.; Abrudan, M.; Abudahab, K.; Argimon, S.; Kekre, M.; Underwood, A.; Stelling, J.; Aanensen, D. M.; The NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance,

doi:10.1101/2021.06.22.449363

bioRxiv · 10.1101/2021.06.22.449363

Genome Sequencing Identifies Previously Unrecognized Klebsiella pneumoniae Outbreaks in Neonatal Intensive Care Units in the Philippines

Carlos, C. C.·Masim, M. A. L.·Lagrada, M. L.·Gayeta, J. M.·Macaranas, P. K. V.·Sia, S. B.·Facun, M. A. M.·Palarca, J. F. C.·Olorosa, A. M.·Cueno, G. A. C.·Abrudan, M.·Abudahab, K.·Argimon, S.·Kekre, M.·Underwood, A.·Stelling, J.·Aanensen, D. M.·The NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance,

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Abstract

BackgroundKlebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least two classes of antibiotics, yet mechanisms and spread of its resistance are not well studied. MethodsA retrospective sequencing survey was performed on carbapenem-, extended spectrum beta-lactam- and cephalosporin-resistant Klebsiella pneumoniae isolated at 20 antimicrobial resistance (AMR) surveillance sentinel sites from 2015-2017. We characterized 259 isolates using biochemical methods, antimicrobial susceptibility testing, and whole genome sequencing (WGS). Known AMR mechanisms were identified. Potential outbreaks were investigated by detecting clusters from epidemiologic, phenotypic and genome-derived data. ResultsPrevalent AMR mechanisms detected include blaCTX-M-15 (76.8%) and blaNDM-1 (37.5%). An epidemic IncFII(Yp) plasmid carrying blaNDM-1 was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (ST). This plasmid was also identified as the main vehicle of carbapenem resistance in 2 previously unrecognized local outbreaks of ST348 and ST283 at 2 different sentinel sites. A third local outbreak of ST397 was also identified but without the IncFII(Yp) plasmid. Isolates in each outbreak site showed identical STs, K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged <1. ConclusionWGS provided an in-depth understanding of the epidemiology of AMR in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of three previously unrecognized Klebsiella outbreaks highlights the utility of WGS in outbreak detection, as well as its importance in public health and in implementing infection control programs. summaryWhole genome sequencing identified three distinct previously unrecognized local outbreaks in a retrospective study in the Philippines, along with an epidemic plasmid carrying antimicrobial resistance genes, highlighting its importance in antimicrobial resistance surveillance, outbreak detection and infection control.

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Carlos, C. C., Masim, M. A. L., Lagrada, M. L., Gayeta, J. M., Macaranas, P. K. V., Sia, S. B., Facun, M. A. M., Palarca, J. F. C., Olorosa, A. M., Cueno, G. A. C., Abrudan, M., Abudahab, K., Argimon, S., Kekre, M., Underwood, A., Stelling, J., Aanensen, D. M., The NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance,. 2021-06-22. Genome Sequencing Identifies Previously Unrecognized Klebsiella pneumoniae Outbreaks in Neonatal Intensive Care Units in the Philippines. https://doi.org/10.1101/2021.06.22.449363

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