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

Background. Klebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least 2 classes of antibiotics, yet mechanisms and spread of its resistance are not well studied. Methods. A 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 through 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. Results. Prevalent AMR mechanisms detected include bla(CTX-M-15) (76.8%) and bla(NDM-1) (37.5%). An epidemic IncFII(Yp) plasmid carrying bla(NDM-1) was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (STs). 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 and K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged < 1 year. Conclusion. WGS provided a better understanding of the epidemiology of multidrug resistant Klebsiella in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of 3 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.