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 multi-drug 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.

Operational challenges of the Philippine Antimicrobial Resistance Surveillance Program during the COVID-19 pandemic

Problem@#Operation of the Philippine Antimicrobial Resistance Surveillance Program (ARSP) has been affected by the coronavirus disease 2019 (COVID-19) pandemic, during which time difficulties in maintaining laboratory functions, staffing levels and participation were reported.@*Context@#The COVID-19 pandemic has increased pressure on most health systems and programmes in the Philippines, including ARSP. As ARSP is the source of national data on antimicrobial resistance (AMR) trends, there are concerns that the negative effects of the pandemic may have impacted the quality of data produced.@*Action@#We describe disruptions to laboratory operations, personnel availability and participation in ARSP surveillance, and their impact on reported data for 2020.@*Outcome@#Surveillance operations were challenged by reallocation of human, infrastructure and financial resources for pandemic response among both the sentinel sites and the coordinating laboratory, the Antimicrobial Resistance Surveillance Reference Laboratory. There was a decrease in the amount of data submitted to the surveillance system, as well as in the number of isolates sent to the reference laboratory for confirmation of bacterial identification and antimicrobial susceptibility testing. Nevertheless, overall performance scores of the sentinel sites for most parameters were comparable to 2019, the year prior to the pandemic.@*Discussion@#The impact of operational changes to ARSP due to the pandemic needs to be considered when analysing AMR surveillance data from 2020. Automation of data submission, good working relationships between the coordinating laboratory and sentinel sites, and supply chain system strengthening were identified as key to maintaining AMR surveillance during the COVID-19 pandemic.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Philippines, 2012–2018

@#Objective: Data are scarce on the prevailing Streptococcus pneumoniae serotypes in the Philippines, including the relative antimicrobial resistance (AMR) of these bacteria. This study is designed to fill that gap by describing the serotype distribution and AMR of S. pneumoniae in the Philippines from 2012 to 2018. Methodology: S. pneumoniae isolates from clinical specimens were collected through the Philippine Department of Health Antimicrobial Resistance Surveillance Program from 1 January 2012 to 31 December 2018. Identification and antimicrobial susceptibility testing (AST) were performed using conventional and automated methods (Vitek2 Compact Automated Machine). AST for penicillin, erythromycin, co-trimoxazole, ceftriaxone and levofloxacin was done following the Clinical and Laboratory Standard Institute recommendations. Serotyping was done through slide agglutination following the Denka Seiken slide agglutination method. Results: From a total of 307 isolates of S. pneumoniae, 32 serotypes were identified; the most frequently occurring were serotypes 1, 3, 5, 4, 18, 19A, 6B, 15 and 14. Many (n=113, 36.53%) of the isolates were from those aged <5 years. Pneumococcal conjugate vaccine (PCV) coverage was as follows: PCV7 (32.69%), PCV10 (54.16%) and PCV13 (69.23%). The overall AMR of invasive S. pneumoniae isolates was low. Penicillin-resistant serotypes were 14, 19, 24, 4, 5, 1, 15, 6 and 32. Discussion: With the inclusion of PCV13 in the National Immunization Program, continued monitoring of the prevailing serotypes of S. pneumoniae isolates in the Philippines is needed to guide disease and AMR control measures.

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.@*Result@#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.

Genomic surveillance of methicillin-resistant Staphylococcus aureus in the Philippines, 2013–2014

@#Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus clones circulating in the Philippines. We sequenced the whole genomes of 116 S. aureus isolates collected in 2013–2014 within the Antimicrobial Resistance Surveillance Program. The multilocus sequence type, spa type, SCCmec type, presence of antimicrobial resistance (AMR) determinants and virulence genes and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. The MRSA population in the Philippines comprised a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South-West Pacific clone but formed a distinct, diverse lineage, with evidence of global dissemination. We showed independent acquisition of resistance to sulfamethoxazole/trimethoprim in various locations and genetic clones but mostly in paediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for eight antibiotics in seven classes. We have made the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific Region and will constitute the genetic background for contextualizing prospective surveillance.

Genomic surveillance of Neisseria gonorrhoeae in the Philippines, 2013–2014

@#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. This first genomic survey of N. gonorrhoeae isolates collected by ARSP will be used to contextualize prospective surveillance. It highlights the importance of genomic surveillance in the Western Pacific and other endemic regions for understanding the spread of drug-resistant gonorrhoea worldwide.

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

@#Pseudomonas aeruginosa is an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized. We sequenced the whole genomes of 176 P. aeruginosaisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-?-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population of P. aeruginosain the Philippines was diverse, with clonal expansions of XDR genomes belonging to multi-locus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, including blaVIM-2, with differences in gene composition and synteny to other P. aeruginosaclass 1 integrons described before. We produced the first comprehensive genomic survey of P. aeruginosain the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.