Antibiotic-associated diarrhoea, Clostridium difficile, and short-chain fatty acids

Scand J Gastroenterol. 1996 Jul;31(7):688-93. doi: 10.3109/00365529609009151.

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.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Cefuroxime / administration & dosage
  • Cefuroxime / adverse effects
  • Cephalosporins / administration & dosage
  • Cephalosporins / adverse effects
  • Clostridioides difficile / isolation & purification*
  • Colon / metabolism
  • Colon / microbiology
  • Diarrhea / chemically induced*
  • Diarrhea / metabolism
  • Diarrhea / microbiology
  • Fatty Acids, Volatile / biosynthesis*
  • Female
  • Humans
  • Liver Transplantation
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nystatin / administration & dosage
  • Nystatin / adverse effects
  • Tobramycin / administration & dosage
  • Tobramycin / adverse effects

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Fatty Acids, Volatile
  • Nystatin
  • Cefuroxime
  • Tobramycin