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.

The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyseSalmonella entericaserovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show potential of travel-associated data to provide informal ″sentinel″ surveillance for such locations. The data indicate ciprofloxacin non-susceptibility (> 1 resistance determinant) is widespread across geographies and genotypes, with high-level resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020), but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. The Consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.

Performing whole genome sequencing (WGS) for the surveillance of antimicrobial resistance offers the ability to determine not only the antimicrobials to which rates of resistance are increasing, but also the evolutionary mechanisms and transmission routes responsible for the increase at local, national, and global scales. To derive WGS-based outputs, a series of processes are required, beginning with sample and metadata collection, followed by nucleic acid extraction, library preparation, sequencing, and analysis. Throughout this pathway there are many data-related operations required (informatics) combined with more biologically focused procedures (bioinformatics). For a laboratory aiming to implement pathogen genomics, the informatics and bioinformatics activities can be a barrier to starting on the journey; for a laboratory that has already started, these activities may become overwhelming. Here we describe these data bottlenecks and how they have been addressed in laboratories in India, Colombia, Nigeria, and the Philippines, as part of the National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance. The approaches taken include the use of reproducible data parsing pipelines and genome sequence analysis workflows, using technologies such as Data-flo, the Nextflow workflow manager, and containerization of software dependencies. By overcoming barriers to WGS implementation in countries where genome sampling for some species may be underrepresented, a body of evidence can be built to determine the concordance of antimicrobial sensitivity testing and genome-derived resistance, and novel high-risk clones and unknown mechanisms of resistance can be discovered.

Objective: Acinetobacter baumannii is an opportunistic nosocomial pathogen that has increasingly become resistant to carbapenems worldwide. In the Philippines, rates of carbapenem resistance and multidrug resistance are above 50%. We undertook a genomic study of carbapenem-resistant A. baumannii in the Philippines to characterize the population diversity and antimicrobial resistance mechanisms. Methods: We sequenced the whole genomes of 117 A. baumannii isolates recovered by 16 hospitals in the Philippines between 2013 and 2014. From the genome sequences, we determined the multilocus sequence type, presence of acquired determinants of antimicrobial resistance and relatedness between isolates. We also compared the phenotypic and genotypic resistance results. Results: Carbapenem resistance was mainly explained by acquisition of the class-D Beta-lactamase gene blaOXA-23. The concordance between phenotypic and genotypic resistance to imipenem was 98.15%, and it was 94.97% overall for the seven antibiotics analysed. Twenty-two different sequence types were identified, including 7 novel types. The population was dominated by the high-risk international clone 2 (i.e. clonal complex 92), in particular by ST195 and ST208 and their single locus variants. Using whole-genome sequencing, we identified local clusters representing potentially undetected nosocomial outbreaks, as well as multi-hospital clusters that indicated interhospital dissemination. Comparison with global genomes suggested that the establishment of carbapenem-resistant international clone 2 in the Philippines is likely the result of clonal expansion and geographical dissemination, and at least partly explained by inadequate hospital infection control and prevention. Discussion: This is the first extensive genomic study of carbapenem-resistant A. baumannii in the Philippines, and it underscores the importance of hospital infection control and prevention measures to contain high-risk clones.