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. However, lack of long-term temporal surveillance data on AMR in countries with high burden like Bangladesh is scarce. Our study explores the AMR trends of Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. Methodology/Principal findings: The typhoid fever surveillance from 1999 to 2022 included two pediatric hospitals and three private clinics in Dhaka, Bangladesh. Blood cultures were performed at treating physicians' discretion; cases were confirmed by microbiological serological, and biochemical tests. Antibiotic susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Over the 24 years of surveillance, we recorded 12,435 culture-confirmed typhoid cases and observed declining resistance to first-line drugs (amoxicillin, chloramphenicol, and cotrimoxazole); multidrug resistance (MDR) decreased from 38% in 1999 to 17% in 2022. Cotrimoxazole consumption dropped from 0.8 to 0.1 Daily defined doses (DDD)/1000/day (1999–2020). Ciprofloxacin non-susceptibility persisted at >90% with unchanged consumption (1.1–1.3 DDD/1000/day, 2002–2020). Low ceftriaxone resistance (<1%) was observed, with slightly 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; first-line antimicrobials could be reintroduced as empirical treatment options for typhoid fever if MDR rates further drops below 5%. The analysis also provides baseline data for monitoring the impact of future interventions like typhoid conjugate vaccines on typhoid burden and associated AMR. Author summary: Our study addresses the pressing issue of antimicrobial resistance (AMR) in Salmonella Typhi, which severely limits treatment options for typhoid fever. Globally, it also raises concerns for a potential pan-oral drug-resistant outbreak. We conducted typhoid fever surveillance, spanning 24 years (1999–2022) across two pediatric hospitals and three private clinics in Dhaka, the capital city of Bangladesh. Our aim was to understand how the AMR landscape of Salmonella Typhi has changed over the years and its correlation with antibiotic consumption. Our findings reveal a notable decline in resistance to first-line drugs including cotrimoxazole, whose decreasing consumption showed a statistically significant correlation with reduced resistance. Ciprofloxacin non-susceptibility persisted at >90%. Ceftriaxone resistance remained low, but there was an upward trend in its minimum inhibitory concentration (MIC). Azithromycin resistance is emerging and currently at <4% but is expected to increase due to the observed 38-fold rise in azithromycin consumption. Taken together, our results establish a baseline to assess the impact of interventions like typhoid conjugate vaccines on typhoid and associated AMR in Bangladesh. Our work also suggests that decreasing resistance to the first line of drugs in Salmonella Typhi may allow for the re-introduction of first line of antimicrobials as empirical treatment options for typhoid fever. [ABSTRACT FROM AUTHOR]