Impact of reducing colistin use on colistin resistance in Escherichia coli isolated from humans and poultry in Indonesia (COINCIDE): A protocol for a multisectoral, transdisciplinary One Health study

Introduction: 

Colistin is a last-resort antimicrobial used to treat infections caused by multidrug-resistant Gram-negative bacteria in humans. In Indonesia, widespread detection of colistin use and resistance in commensal Escherichia coli from poultry, particularly broilers, led to a national ban on its use in livestock effective since July 1st, 2020. However, the impact of this policy intervention on colistin resistance in both humans and livestock has not yet been evaluated. The COINCIDE study aims to investigate the ban's effect on colistin resistance, compliance, and transmission dynamics of resistance between humans and poultry. 

Methods and analysis: 

COINCIDE will: (i) assess phenotypic and genotypic colistin resistance in E. coli from humans and poultry; (ii) estimate transmission of colistin resistant E. coli between humans and animals; (iii) explore colistin and antimicrobial use (AMU) at the community level; (iv) identify social and cultural factors driving AMU; and (v) strengthen multisectoral One Health collaboration. Post-ban sampling will be conducted in three districts of Central Java Province (Klaten, Karanganyar, and Sukoharjo), where pre-ban samples were already available. We will recruit participants from primary healthcare centers (PHC) (n = 683), poultry farmers (n = 120), and visit a total of 60 small-scale layer farms. Broiler isolates (n = 2865) from Indonesia's routine antimicrobial resistance (AMR) surveillance (2018–2023) will also be included. In terms of sample collection, post-ban samples will include rectal swabs from patients visiting PHC and farmers and boot swabs from small-scale layer farms. Colistin resistance will be screened using CHROMagar COL-APSE agar medium and confirmed by broth microdilution. Results of long-read whole-genome sequencing will identify resistance mechanisms and transmission pathways. A qualitative ethnography work will include participant observation and informal conversations during field visits, alongside in-depth interviews with healthcare professionals and stakeholders. “Drug bag” method interviews will assess antimicrobial use, access, and drivers at the community level. Simulated patient visits to pharmacies and local shops (warung or toko obat), and interviews with agrovet outlets and poultry shops will be conducted to evaluate compliance with antimicrobial sales regulations.

Conclusion: 

By integrating microbiological, epidemiological, policy, and social science data, findings from the COINCIDE study will provide a strong scientific basis to inform AMR policies in Indonesia, with potential significance to inform other countries across Southeast Asia.