Genomic surveillance of methicillin-resistant Staphylococcus aureus in the Philippines, 2013–2014
MRSA surveillance in the Philippines
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.
Lee AS, de Lencastre H, Garau J, Kluytmans J, Malhotra-Kumar S, Peschel A, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers. 2018;4:18033.
Kang GS, Jung YH, Kim HS, Lee YS, Park C, Lee KJ, et al. Prevalence of Major Methicillin-Resistant Staphylococcus aureus Clones in Korea Between 2001 and 2008. Ann Lab Med. 2016;36(6):536-41.
Song JH, Hsueh PR, Chung DR, Ko KS, Kang CI, Peck KR, et al. Spread of methicillin-resistant Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study. J Antimicrob Chemother. 2011;66(5):1061-9.
Chuang YY, Huang YC. Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Asia. Lancet Infect Dis. 2013;13(8):698-708.
Ko KS, Lee JY, Suh JY, Oh WS, Peck KR, Lee NY, et al. Distribution of major genotypes among methicillin-resistant Staphylococcus aureus clones in Asian countries. J Clin Microbiol. 2005;43(1):421-6.
Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, et al. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic. Genome Res. 2013;23(4):653-64.
Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest. 2014;124(7):2836-40.
Antimicrobial Resistance Surveillance Reference Laboratory, Research Institute for Tropical Medicine, Department of Health. ARSP 2014 Annual Report Data Summary. 2015. Contract No.: 05/08/2019.
World Health Organization. Global antimicrobial resistance surveillance system (GLASS) report: early implementation 2016-2017. 2017.
Clinical and Laboratory Standards Institute. M100-S26 Performance Standards for Antimicrobial Susceptibility Testing. 26th Edition. 2016.
Argimon S, Masim MA, Gayeta JM, Lagrada ML, Macaranas PK, Cohen V, et al. See and Sequence: Integrating Whole-Genome Sequencing Within the National Antimicrobial Resistance Surveillance Program in the Philippines. BioRxiv. 2019.
Page AJ, De Silva N, Hunt M, Quail MA, Parkhill J, Harris SR, et al. Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data. Microb Genom. 2016;2(8):e000083.
Hunt M, Mather AE, Sanchez-Buso L, Page AJ, Parkhill J, Keane JA, et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microb Genom. 2017;3(10):e000131.
Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018;3:124.
Bartels MD, Petersen A, Worning P, Nielsen JB, Larner-Svensson H, Johansen HK, et al. Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2014;52(12):4305-8.
Inouye M, Dashnow H, Raven LA, Schultz MB, Pope BJ, Tomita T, et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 2014;6(11):90.
Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA, Bentley SD, et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res. 2015;43(3):e15.
Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T, Keane JA, et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom. 2016;2(4):e000056.
Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30(9):1312-3.
Price MN, Dehal PS, Arkin AP. FastTree 2--approximately maximum-likelihood trees for large alignments. PLoS One. 2010;5(3):e9490.
Harkins CP, Pichon B, Doumith M, Parkhill J, Westh H, Tomasz A, et al. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol. 2017;18(1):130.
Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, et al. How clonal is Staphylococcus aureus? J Bacteriol. 2003;185(11):3307-16.
Nahmias A, Sakurai N, Blumberg R, Doe Ge A, Sulzer C. The Staphylococcus "80/81 complex: epidemiological and laboratory observations. J Infect Dis. 1961;109:211-22.
Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G, et al. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet. 2005;365(9466):1256-8.
McAdam PR, Templeton KE, Edwards GF, Holden MT, Feil EJ, Aanensen DM, et al. Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci U S A. 2012;109(23):9107-12.
Aanensen DM, Feil EJ, Holden MT, Dordel J, Yeats CA, Fedosejev A, et al. Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe. MBio. 2016;7(3).
Arias CA, Reyes J, Carvajal LP, Rincon S, Diaz L, Panesso D, et al. A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries. Antimicrob Agents Chemother. 2017;61(10).
McCarthy AJ, Breathnach AS, Lindsay JA. Detection of mobile-genetic-element variation between colonizing and infecting hospital-associated methicillin-resistant Staphylococcus aureus isolates. J Clin Microbiol. 2012;50(3):1073-5.
Reuter S, Torok ME, Holden MT, Reynolds R, Raven KE, Blane B, et al. Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland. Genome Res. 2016;26(2):263-70.
Gordon NC, Price JR, Cole K, Everitt R, Morgan M, Finney J, et al. Prediction of Staphylococcus aureus antimicrobial resistance by whole-genome sequencing. J Clin Microbiol. 2014;52(4):1182-91.
Coll F, Harrison EM, Toleman MS, Reuter S, Raven KE, Blane B, et al. Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community. Sci Transl Med. 2017;9(413).