Trends in antimicrobial resistance amongst Salmonella Typhi in Bangladesh: a 24-year retrospective observational study (1999–2022)

Background Rising antimicrobial resistance (AMR) in Salmonella Typhi restricts typhoid treatment options, heightening concerns for pan-oral drug-resistant outbreaks. Bangladesh contemplates introducing typhoid conjugate vaccine (TCV) to address the typhoid burden and AMR. However, large-scale surveillance data on typhoid AMR in Bangladesh is scarce. Objective This study explores the AMR trends in Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. Methods Our typhoid fever surveillance included two pediatric hospitals and three private clinics in Dhaka, Bangladesh, spanning 1999 to 2022. Blood cultures were performed at physicians’ discretion; cases were confirmed by microbiological culture, serological, and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Results Our 24-year surveillance, encompassing 12,435 Salmonella Typhi cases, revealed declining trends in first-line drugs (amoxicillin, chloramphenicol, cotrimoxazole) and multidrug resistance (MDR; 38% to 17%, 1999–2022). Cotrimoxazole consumption dropped, 0.8 to 0.1 DDD/1000/day (1999–2020). Ciprofloxacin non-susceptibility persisted (>90%) with unchanged consumption (1.1-1.3 DDD/1000/day, 2002–2020). Low ceftriaxone resistance (<1%) was observed, with rising MIC (0.03 to 0.12 mg/L, 1999–2019). Azithromycin consumption increased (0.1 to 3.8 DDD/1000/day, 1999–2020), but resistance remained ≤4%. Conclusion Our study highlights declining MDR amongst Salmonella Typhi in Bangladesh, thus reintroducing first-line antimicrobials could work as an empirical treatment option for typhoid fever. Our analysis provides a baseline for monitoring the impact of future interventions, including the TCV, on typhoid burden and associated AMR. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work presented here was supported by Gavi, the Vaccine Alliance, through the World Health Organization-supported Invasive Bacterial Vaccine Preventable Diseases study (grant numbers 201588766, 201233523, 201022732, 200749550), by leveraging the Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP), by the Bill and Melinda Gates Foundation through SEAP (grant number INV-008335), and by the Child Health Research Foundation (CHRF). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Review Committee of Bangladesh Shishu Hospital and Institute (BSHI) gave ethical approval for all protocols of this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant study data are provided in the Supplementary Data S1 of the article.