Epidemiology and antimicrobial resistance profile of invasive non-typhoidal Salmonella from the Philippines Antimicrobial Resistance Surveillance Program, 2014-2018.

Objective: The epidemiology of invasive non-typhoidal Salmonella (iNTS) in the Philippines is not well elaborated. The present study describes the serotype distribution and antimicrobial susceptibility patterns of iNTS in the Philippines from 2014 to 2018. Methods: Invasive NTS isolates were collected through the Department of Health's Antimicrobial Resistance Surveillance Program (ARSP). The identification of the isolates was confirmed using automated (Vitek®, bioMérieux, Marcy l'Étoile, France) and conventional methods. The isolates were serotyped using the slide agglutination method, and susceptibility testing was performed using Clinical and Laboratory Standards Institute guidelines. Demographic data were collected from the ARSP database. Results: There were 138 isolates collected from human invasive specimens with 97.8% from blood samples. The most common serotypes were Salmonella Enteritidis (n = 84, 60.9%) and Salmonella Typhimurium (n = 18, 13.0%). Most of the isolates were from males (n = 88, 63.8%) and from the 0-5-year age group (n = 61, 44.2%). The proportions of iNTS isolates resistant to first-line antibiotics were as follows: ampicillin (23.2%), chloramphenicol (9.6%), ciprofloxacin (8.7%), ceftriaxone (2.2%) and trimethoprim-sulfamethoxazole (8.8%). The proportion of isolates with multidrug resistance was 13.0% (18/138) with the most common resistance profile being resistance to ampicillin-chloramphenicol-ciprofloxacin from Salmonella Enteritidis isolates (n = 5). Discussion: Resistance to first-line antibiotics limits the therapeutic choices for Salmonella infection. Relevant local antimicrobial resistance data on iNTS may support appropriate empiric therapy among vulnerable populations.

Genomic surveillance of Pseudomonas aeruginosa in the Philippines, 2013-2014.

Pseudomonas aeruginosa is an opportunistic pathogen that often causes nosocomial infections resistant to treatment. Rates of antimicrobial resistance (AMR) are increasing, as are rates of multidrug-resistant (MDR) and possible extensively drug-resistant (XDR) infections. Our objective was to characterize the molecular epidemiology and AMR mechanisms of this pathogen. We sequenced the whole genome for each of 176 P. aeruginosa isolates collected in the Philippines in 2013-2014; derived the multilocus sequence type (MLST), presence of AMR determinants and relatedness between isolates; and determined concordance between phenotypic and genotypic resistance. Carbapenem resistance was associated with loss of function of the OprD porin and acquisition of the metallo-ß-lactamase (MBL) gene bla VIM. Concordance between phenotypic and genotypic resistance was 93.27% overall for six antibiotics in three classes, but varied among aminoglycosides. The population of P. aeruginosa was diverse, with clonal expansions of XDR genomes belonging to MLSTs ST235, ST244, ST309 and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, and of transfer between hospitals. Most of the ST235 genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the Philippines. In addition, long-read sequencing of one representative XDR ST235 isolate identified an integron carrying multiple resistance genes (including bla VIM-2), with differences in gene composition and synteny from the P. aeruginosa class 1 integrons described previously. The survey bridges the gap in genomic data from the Western Pacific Region and will be useful for ongoing surveillance; it also highlights the importance of curtailing the spread of ST235 within the Philippines.

Genomic surveillance of Acinetobacter baumannii in the Philippines, 2013-2014.

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 ß-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 multihospital 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.

Integrating whole-genome sequencing within the National Antimicrobial Resistance Surveillance Program in the Philippines.

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 middle-income 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.