<p>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 <i>Salmonella enterica</i> serovar Typhimurium and treated them for 24&#xa0;h with non-toxic concentrations of caffeine (0.05–5&#xa0;µg/ml) plus gentamicin (10&#xa0;µg/ml). Subsequently, Swiss mice were orally challenged with <i>S.</i> Typhimurium and received daily intraperitoneal doses of caffeine (0.05-5&#xa0;mg/kg) plus gentamicin (10&#xa0;mg/kg) for five days post-infection. Macrophages treated with 5&#xa0;µg/ml caffeine plus 10&#xa0;µg/ml gentamicin exhibited significantly higher viability and a marked reduction in intracellular bacterial load. Lower caffeine doses (0.05 and 0.5&#xa0;µg/ml) failed to preserve cell viability due to uncontrolled bacterial proliferation. Mice receiving gentamicin – either alone or combined with 5&#xa0;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.</p>

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

  • Esther de Souza Silva,
  • Roseane Thays dos Santos Rocha,
  • Joyce Nayara Gomes da Silva,
  • Victor Vinicius Pereira Ribeiro,
  • Islana Silva Ponte,
  • Isabela Cristina Bandeira Fraga,
  • Camila Sant Ana de Oliveira,
  • Viviane Moreira Lima Galvão,
  • Alison Hideo Jolo Silva,
  • Valdemiro Amaro da Silva Junior,
  • José Vitor Lima-Filho

摘要

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.