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.

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health, and of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but studies of the genomic epidemiology of gonorrhoea in the Philippines are lacking.We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013-2014 by the ARSP. The multi-locus sequence type, multi-antigen sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Ten out of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, mostly linked to the presence of blaTEM gene, the S91F mutation in the gyrA gene, and the tetM gene, respectively. None of the isolates were resistant to azithromycin, ceftriaxone or cefixime, although we identified the A24-deletion in the mtrR promoter in one isolate. The concordance between phenotypic and genotypic resistance was 92.38% overall for 5 antibiotics in 4 classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the NG-MAST types and the tree. Comparison with global genomes placed the Philippine genomes within global Lineage A and led to the identification of an international transmission route.This first genomic survey of N. gonorrhoeae isolates collected by ARSP will be used to contextualize ongoing prospective surveillance, and it highlights the importance of genomic surveillance in the Western Pacific and other endemic regions to understand the spread of drug-resistant gonorrhoea worldwide.

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines. We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013–2014 by ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence of the blaTEM gene, the S91F mutation in the gyrA gene and the tetM gene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the N. gonorrhoeae multiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to the identification of an international transmission route.