Antibiotic-associated diarrhoea, Clostridium difficile, and short-chain fatty acids.
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.
Hove
H
H
Dept. of Medicine A, Rigshospitalet, University of Copenhagen, Denmark.
Tvede
M
M
Mortensen
P B
PB
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002444:Cefuroxime / Q000008:administration & dosage / Q000009:adverse effects; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology; D005232:Fatty Acids, Volatile / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009761:Nystatin / Q000008:administration & dosage / Q000009:adverse effects; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005232:Fatty Acids, Volatile; D009761:Nystatin; D002444:Cefuroxime; D014031:Tobramycin