Ups and downs in the experimental treatment of murine typhoid fever using gentamicin combined with caffeine.

Abstract

This study assessed whether combining the aminoglycoside gentamicin with caffeine enhances antimicrobial efficacy in a murine typhoid model. We infected murine peritoneal macrophages in vitro with Salmonella enterica serovar Typhimurium and treated them for 24 h with non-toxic concentrations of caffeine (0.05–5 µg/ml) plus gentamicin (10 µg/ml). Subsequently, Swiss mice were orally challenged with S. Typhimurium and received daily intraperitoneal doses of caffeine (0.05-5 mg/kg) plus gentamicin (10 mg/kg) for five days post-infection. Macrophages treated with 5 µg/ml caffeine plus 10 µg/ml gentamicin exhibited significantly higher viability and a marked reduction in intracellular bacterial load. Lower caffeine doses (0.05 and 0.5 µg/ml) failed to preserve cell viability due to uncontrolled bacterial proliferation. Mice receiving gentamicin – either alone or combined with 5 mg/kg caffeine – showed reduced hepatic bacterial burdens and milder histopathological damage. Notably, only the higher caffeine dose enhanced gentamicin’s efficacy; lower caffeine concentrations antagonized the antibiotic’s activity.