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

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.