National networks of laboratory-based surveillance of antimicrobial resistance (AMR) monitor resistance trends and disseminate these data to AMR stakeholders. Whole-genome sequencing (WGS) can support surveillance by pinpointing resistance mechanisms and uncovering transmission patterns. However, genomic surveillance is rare in low-and middleincome countries. Here, we implement WGS within the established Antimicrobial Resistance Surveillance Program of the Philippines via a binational collaboration. In parallel, we characterize bacterial populations of key bug-drug combinations via a retrospective sequencing survey. By linking the resistance phenotypes to genomic data, we reveal the interplay of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying the expansion of specific resistance phenotypes that coincide with the growing carbapenem resistance rates observed since 2010. Our results enhance our understanding of the drivers of carbapenem resistance in the Philippines, while also serving as the genetic background to contextualize ongoing local prospective surveillance.

Background. Drug-resistant bacterial infections constitute a growing threat to public health globally. National networks of laboratory-based surveillance of antimicrobial resistance (AMR) monitor the emergence and spread of resistance and are central to the dissemination of these data to AMR stakeholders. Whole-genome sequencing (WGS) can support these efforts by pinpointing resistance mechanisms and uncovering transmission patterns. We implemented WGS within the established Antimicrobial Resistance Surveillance Program (ARSP) of the Philippines. We aimed to employ WGS to characterize bacterial populations and dissect resistance phenotypes of key bug-drug combinations, thus establishing a genetic background to contextualize local prospective surveillance.Methods. We sequenced the genomes from eight bacterial pathogens collected between 2013 and 2014 by the ARSP, and conducted phylogenetic analyses, in silico genotyping, genomic predictions of AMR, and characterization of key plasmids carrying carbapenemase genes. Here, we focus on carbapenemase-producing organisms.Findings. ARSP phenotypic data indicated increasing carbapenem resistance for Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli, with marked expansion of specific resistance phenotypes. By linking resistance phenotypes to genomic data, we revealed the diversity of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying this expansion. We discovered a previously unidentified plasmid-driven hospital outbreak of carbapenem-resistant K. pneumoniae, uncovered the interplay of carbapenem resistance genes and plasmids in the geographic circulation of international epidemic K. pneumoniae ST147, and found that carbapenem-resistant E. coli ST410 were represented by diverse lineages of global circulation that both conserved international plasmids and acquired plasmids of local circulation.Conclusions. WGS provided an enhanced understanding of the interplay between strains, genes and vehicles driving the dissemination of carbapenem resistance in the Philippines. We generated a blueprint for the integration of WGS and genomic epidemiology into an established national system of laboratory-based surveillance of AMR through international collaboration. Continued prospective sequencing, capacity building and collaboration will strengthen genomic surveillance of AMR in the Philippines and the translation of genomic data into public-health action.

Background Increasing antimicrobial resistance (AMR) in Salmonella has been observed in the Philippines. We aimed to characterise the population and AMR mechanisms of Salmonella with whole genome sequencing (WGS) and compare it with laboratory surveillance methods. Methods The serotype, multilocus sequence type, AMR genes and relatedness between isolates were determined from the genomes of 148 Salmonella Typhi (S. Typhi) and 65 non-typhoidal Salmonella (NTS) collected by the Antimicrobial Resistance Surveillance Program during 2013–2014. Genotypic serotypes and AMR prediction were compared with phenotypic data. Results AMR rates in S. Typhi were low, with sparse acquisition of mutations associated with reduced susceptibility to fluoroquinolones or extended-spectrum beta-lactamases (ESBL) genes. By contrast, 75% of NTS isolates were insusceptible to at least one antimicrobial, with more than half carrying mutations and/or genes linked to fluoroquinolone resistance. ESBL genes were detected in five genomes, which also carried other AMR determinants. The population of S. Typhi was dominated by likely endemic genotype 3.0, which caused a putative local outbreak. The main NTS clades were global epidemic S. Enteritidis ST11 and S. Typhimurium monophasic variant (I,4,[5],12: i: -) ST34. Conclusion We provide the first genomic characterisation of Salmonella from the Philippines and evidence of WGS utility for ongoing surveillance.

Increasing antimicrobial resistance (AMR) in Salmonella has been observed in the Philippines. This study aims to utilize whole genome sequencing (WGS) to characterize the population and AMR mechanisms of Salmonella captured by the Philippine Antimicrobial Resistance Surveillance Program (ARSP) and contrast to traditional laboratory methods. We sequenced the whole genomes of 148 SalmonellaTyphi (S. Typhi) and 65 non-typhoidal Salmonella (NTS) collected in the Philippines in 2013-2014. From the genome sequences, we determined the serotype, multilocus sequence type, presence of determinants of antimicrobial resistance and relatedness between isolates. We also compared the genotypic predictions of serotype and AMR to the phenotypic data. AMR rates in S. Typhi were low, with sparse acquisition of mutations associated with reduced susceptibility to fluoroquinolones or extended-spectrum beta-lactamases (ESBL) genes. In contrast, three quarters of NTS isolates were insusceptible to at least one antimicrobial, with more than half carrying mutations and/or genes linked to resistance to fluoroquinolones. ESBL genes were detected in five genomes that also carried other AMR determinants. The population of S. Typhi was dominated by the likely endemic genotype 3.0, which also caused of a putative local outbreak susceptible to antibiotics. The main NTS clades were global epidemic S. Enteritidis ST11 and the monophasic variant of S. Typhimurium (I 4,[5],12:i:-) ST34, which had frequently been serotyped as S. Typhimurium in the laboratory. This was the first time that Salmonella isolated from the Philippines were characterized by WGS and we provide evidence of its utility for ongoing surveillance at the ARSP.