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

Holly O Espiritu,David M Aanensen,Karis D Boehme,Jeremiah Chilam,Silvia Argimón,Janice B Borlasa,Charmian M Hufano,Alfred S Villamin,Victoria Cohen,Polle Krystle V Macaranas ,John Stelling,Agnettah M Olorosa ,Khalil Abudahab,Lara Fides T Hernandez ,Manuel C Jamoralín ,June M Gayeta ,Janziel C Palarca,Marietta L Lagrada ,Benjamin Jeffrey,Melissa Ana Masim ,Matthew T G Holden,Sonia Sia ,Celia C Carlos,Marilyn T Limas

doi:10.1038/s41467-020-16322-5

Abstract

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.

Highlights

Antimicrobial resistance (AMR) is an increasingly serious threat to global public health and the economy that requires concerted action across countries, government sectors and non-government organizations[1]
National networks of laboratory-based surveillance are a key pillar within the Global Action Plan to combat AMR, with the reference laboratory playing a central role in the dissemination of surveillance data to local, national and international stakeholders
By complementing laboratory data with Whole-genome sequencing (WGS) and linking the operational units of laboratory and genomic surveillance, we revealed a diversity of genetic lineages, AMR mechanisms and vehicles underlying the expansion of carbapenem resistance phenotypes (Figs. 1a and 3)

Summary

Introduction

Antimicrobial resistance (AMR) is an increasingly serious threat to global public health and the economy that requires concerted action across countries, government sectors and non-government organizations[1]. WGS is routinely used for infectious disease epidemiology in several high-income countries around the world, where it has improved outbreak investigations and epidemiological surveillance[10,11] and enhanced our knowledge of the spread of antimicrobial-resistant strains and their resistance mechanisms[12,13]. Implementation of WGS within existing national surveillance systems in low- and middle-income countries (LMICs) has the potential to enhance local prevention and control of resistant infections in a sustainable and equitable manner. We provide exemplars from the retrospective sequencing survey that highlight how the granular view of strain-gene-vehicle in carbapenem-resistant populations at the local, national and global operational scales can be leveraged for surveillance of AMR and public health

Methods

Results

Conclusion