Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999–2021

Abstract

Background

Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh.

Methods

From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines.

Results

Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin.

Conclusions

Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

Author summary

Typhoid and paratyphoid fever, caused by Salmonella Typhi and Paratyphi A respectively, are common in areas lacking safe water and optimum infrastructure. With increasing multidrug resistance in Salmonella Typhi, newer antimicrobials like ceftriaxone and azithromycin are frequently prescribed for the empirical treatment of both typhoid and paratyphoid fever. This is because Salmonella Paratyphi A is less prevalent in most endemic countries, and typhoid and paratyphoid fever are often symptomatically indistinguishable. In this study, we conducted comprehensive surveillance of Salmonella Paratyphi A in Bangladesh over a period of 23 years and identified 2,725 blood culture-confirmed paratyphoid cases. Our findings indicate that Salmonella Paratyphi A remained susceptible to most of the older generation of antibiotics as over 97% of the isolates continue to be susceptible to ampicillin, chloramphenicol and cotrimoxazole, and no isolate detected was resistant to all three drugs. Although 99% of the isolates exhibited reduced fluoroquinolone susceptibility, 99% and 100% were sensitive to azithromycin and ceftriaxone. These findings are important and can guide evidence-based policy decisions for the empirical treatment of paratyphoid fever. While newer antimicrobials such as azithromycin and ceftriaxone remain effective, successful implementation of typhoid conjugate vaccines and rapid diagnostics may re-enable the use of older generation antibiotics for empirical treatment of enteric fever without compromising the treatment efficacy. This approach can contribute to the antimicrobial stewardship efforts by preserving critically important antimicrobials such as ceftriaxone and azithromycin for the treatment of numerous other multidrug-resistant bacterial infections.