Bacterial Genomics for National Antimicrobial Resistance Surveillance in Cambodia

Author:

Yek Christina12ORCID,Lon Chanthap1,Chea Sophana1ORCID,Lay Sreyngim1,Oum Meng Heng1,Tang Gechlang1,Lon Chansothea1,Pacheco Andrea R1,Drobish Ian3,Stuehser Reagan1,Ly Sokna1,Sath Ratanak1,Srouen Malin4,Bin Chamrouen5,Chak Chanthou6,Seang Sosorphea6,Srey Viso7,Chhor Bunna7,Nhem Somary8,Chiek Sivhour9,Dork Rina9,Dekker John P10,Seng Heng11,Krang Sidonn11,Ly Sovann11,Manning Jessica E12

Affiliation:

1. International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases , Phnom Penh , Cambodia

2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases , Rockville, Maryland , USA

3. Critical Care Medicine Department, National Institutes of Health Clinical Center , Bethesda, Maryland , USA

4. Department of Laboratory Medicine, Preah Kossomak Hospital , Phnom Penh , Cambodia

5. Department of Laboratory Medicine, Siem Reap Hospital , Siem Reap , Cambodia

6. Department of Laboratory Medicine, Takeo Provincial Hospital , Takeo , Cambodia

7. Department of Laboratory Medicine, National Pediatric Hospital , Phnom Penh , Cambodia

8. Department of Laboratory Medicine, Kampong Cham Provincial Hospital , Kampong Cham , Cambodia

9. Department of Laboratory Medicine, Battambang Provincial Referral Hospital , Battambang , Cambodia

10. Bacterial Pathogenesis and Antimicrobial Resistance Unit, National Institute of Allergy and Infectious Diseases , Bethesda, Maryland , USA

11. Communicable Disease Control Department, Ministry of Health , Phnom Penh , Cambodia

Abstract

Abstract Background Antimicrobial resistance (AMR) surveillance in low- and middle-income countries (LMICs) often relies on poorly resourced laboratory processes. Centralized sequencing was combined with cloud-based, open-source bioinformatics solutions for national AMR surveillance in Cambodia. Methods Blood cultures growing gram-negative bacteria were collected at 6 Cambodian hospitals (January 2021 to October 2022). Isolates were obtained from pure plate growth and shotgun DNA sequencing performed in country. Using public nucleotide and protein databases, reads were aligned for pathogen identification and AMR gene characterization. Multilocus sequence typing was performed on whole-genome assemblies and haplotype clusters compared against published genomes. Results Genes associated with acquired resistance to fluoroquinolones were identified in 59%, trimethoprim/sulfamethoxazole in 45%, and aminoglycosides in 52% of 715 isolates. Extended-spectrum β-lactamase encoding genes were identified in 34% isolates, most commonly blaCTX-M-15, blaCTX-M-27, and blaCTX-M-55 in Escherichia coli sequence types 131 and 1193. Carbapenemase genes were identified in 12% isolates, most commonly blaOXA-23, blaNDM-1, blaOXA-58, and blaOXA-66 in Acinetobacter species. Phylogenetic analysis revealed clonal strains of Acinetobacter baumannii, representing suspected nosocomial outbreaks, and genetic clusters of quinolone-resistant typhoidal Salmonella and extended-spectrum β-lactamase E. coli cases suggesting community transmission. Conclusions With accessible sequencing platforms and bioinformatics solutions, bacterial genomics can supplement AMR surveillance in LMICs.

Funder

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bill and Melinda Gates Foundation

Publisher

Oxford University Press (OUP)

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