Journal of Antimicrobial Agents

Background: Typhoidal infections pose significant public health concern on a global scale. Chloramphenicol and co-trimoxazole (trimethoprimsulfamethoxazole) are both antibiotics used to treat typhoidal infections, often with co-trimoxazole considered a suitable alternative to chloramphenicol due to the potential serious side effects associated with chloramphenicol. But due to increasing reports over two decades on typhoidal infectious antibiotic resistance to these antibiotics, there necessitates exploration of alternative treatment strategies. This study investigated the in vitro antibacterial potency and synergistic effect of chloramphenicol and co-trimoxazole combination against Salmonella typhi (ATCC 334538).

Method: The antibacterial activity of chloramphenicol and co-trimoxazole, both alone and in combination at ratios of 1:1, 2:1, 4:1, 8:1, and 1:8 respectively, were assessed against S. typhi. Minimum Inhibitory Concentrations (MICs) were determined for each drug and in combination and were compared with their standard MICs according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The Fractional Inhibitory Concentration Index (FICI) was calculated to characterize the interaction as synergistic (FICI ≤ 0.5), additive (0.54). Clinical breakpoints were determined according to CLSI guidelines.

Results: The Salmonella typhi exhibited resistance to chloramphenicol and co-trimoxazole when used alone, with MICs of 64 μg/mL and 16 μg/ mL, respectively. The combination of chloramphenicol and co-trimoxazole however significantly reduced the MICs, ranging from 2-16 μg/mL for chloramphenicol and 4-8 μg/mL for co-trimoxazole. Synergistic activity was observed with combination ratios of 4:1 and 8:1. Additive effects were seen with ratios of 1:1 and 2:1. A ratio of 1:8 demonstrated indifference. No antagonistic activity was detected.

Conclusion: These in vitro findings suggest that combining chloramphenicol and co-trimoxazole may be a relevant strategy for treating typhoidal infections, as synergistic combinations effectively lowered the MICs of both drugs against S. typhi. Further research, including in vivo studies and clinical trials, is warranted to evaluate the clinical efficacy and safety of this drug combination.