Antibiotic-Associated Diarrhoea, Clostridium difficile, and Short-Chain Fatty Acids

Abstract

Background: It has been hypothesized that Clostridium difficile and decreased colonic production of short-chain fatty acids (SCFAs) cause the development of antibiotic-associated diarrhoea. We therefore wanted to investigate the effects of an intensive and uniform antibiotic therapy on faecal SCFAs concentrations, C. difficile, and extent of diarrhoea. Methods: Fifteen liver-transplanted patients who received oral bowel flora suppression therapy (6.3 g cefuroxime, 0.6 g tobramycin, and 0.5 g nystatin three times daily) were studied for 12 days before and 12 days after discontinuation of therapy. Results: Thirteen of the 15 patients (87%) developed diarrhoea. Colonic fermentation was negligible in all patients, judged by very low levels of faecal SCFAs (<10 mmol/l). Diarrhoea lessened as suppression therapy proceeded despite continuous low levels of SCFAs. Initial stool frequency of 4.1 ± 0.6 and viscosity of 2.5 ± 0.2 per day (on a scale of 1-3; mean ± SE) decreased to 2.2 ± 0.5 (p = 0.0009) and 1.6 ± 0.2 (p = 0.003) per day, respectively, just before cessation of suppression therapy. Both SCFAs and stool habits normalized within days after discontinuation of antibiotics. Only a few samples from 2 patients were culture-positive for C. difficile during therapy, whereas 9 of the 15 patients (60%) became culture-positive (6 cytotoxin-positive) after cessation of suppression therapy at a time when none had diarrhoea. Conclusions: Intensive treatment with antibiotics directed against the colonic flora resulted in diarrhoea in the vast majority of patients, but the diarrhoea was self-limiting despite continual antibiotic treatment and very low faecal concentrations of SCFAs. C. difficile was not associated with antibiotic-associated diarrhoea but was a common finding after treatment with antibiotics was stopped at the time when diarrhoea had ceased.

Key Words:

• Antibiotic-associated diarrhoea
• Clostridium difficile
• short-chain fatty acids
• volatile fatty acids