In vitro pharmacological interaction of caffeine and first-line antibiotics is antagonistic against clinically important bacterial pathogens

Acta Biochim Pol. 2017;64(2):255-263. doi: 10.18388/abp.2016_1327. Epub 2016 Jun 14.


The in vitro antibacterial activity of pure caffeine powder and its interaction with first line antibiotic against bacterial isolates were investigated with the macrobroth dilution and the checkerboard assay methods. This study showed that caffeine and the antibiotics exhibited various degrees of antibacterial activities. While caffeine had MICs ranging between 67.19 and 268.75 µg/ml, chloramphenicol was characterized by MICs between 0.98 and 31.25 µg/ml, kanamycin - 15.63-62.5 µg/ml, nalidixic acid - 0.49-250 µg/ml, erythromycin - 0.49-62.5 µg/ml, tetracycline - 1.99-62.5 µg/ml and metronidazole - 15.63-31.25 µg/ml. Combining ½ MICs and MICs of caffeine with the antibiotics as well as direct combination of caffeine and the antibiotics resulted in significant reduction of antibiotics' effectiveness. The fractional inhibitory concentration index (FICI) for the combination of ½ MICs of caffeine with different antibiotics showed antagonistic interactions with the antibiotics except kanamycin which had additive and indifferent interactions with caffeine. The FICI of the MICs of caffeine combined with antibiotics showed a reduction in the number of antagonistic interactions as chloramphenicol, nalidixic acid and erythromycin showed some indifferent interactions while kanamycin was the only antibiotic that showed indifferent interaction against all the bacterial isolates. The direct combination of caffeine and the antibiotics resulted in significant antagonistic interactions higher than in the case when caffeine, at the ½ MICs and MICs, was combined with the antibiotics. Although caffeine demonstrated significant antibacterial activity against the selected bacterial isolates, its combination with the selected antibiotics resulted in significant antagonistic interactions. Caffeine should not be combined with antibiotics as this could result in serious therapeutic failure and, possibly, drug toxicity in vivo.

Keywords: antagonistic effects; antibacterial activity; antibiotics; bacterial isolates; caffeine.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / pathogenicity
  • Caffeine / chemistry
  • Caffeine / pharmacology*
  • Chloramphenicol / pharmacology
  • Drug Synergism*
  • Erythromycin / pharmacology
  • Humans
  • Kanamycin / pharmacology
  • Metronidazole / pharmacology
  • Microbial Sensitivity Tests
  • Nalidixic Acid / pharmacology
  • Tetracycline / pharmacology


  • Anti-Bacterial Agents
  • Metronidazole
  • Nalidixic Acid
  • Caffeine
  • Kanamycin
  • Erythromycin
  • Chloramphenicol
  • Tetracycline