Antibiotic-associated colitis: an in vitro investigation of the effects of antibiotics on intestinal motility.

1 Nine antibiotic compounds in common use were studied to determine their ability to affect intestinal motility in vitro, in the guinea-pig ileum and rabbit colon. 2 Ampicillin, doxycycline, mecillinam and metronidazole were without effect over a concentration range which included typical serum levels found when these drugs are used therapeutically. 3 Clindamycin, gentamicin, kanamycin, pivmecillinam and trimethoprim were all found to inhibit evoked and reflex responses of the guinea-pig ileum but only clindamycin and trimethoprim also affected evoked responses of the rabbit colon. 4 Kanamycin and gentamicin appeared to have a predominantly pre-junctional action, pivmecillinam and trimethoprim a predominantly post-junctional action. Clindamycin had a pre-junctional action at low concentrations and long exposure times, and a post-junctional action at high concentrations and short exposure times. 5 The concentration of each antibiotic required to inhibit the peristaltic reflex of the guinea-pig ileum was less than that required to inhibit its responses to electrical stimulation or exogenous acetylcholine or histamine but greater than the serum levels associated with their respective use in therapeutic doses. 6 A sequence of events whereby antibiotic-induced alterations in gastro-intestinal motility could lead to the development of pseudomembranous colitis is proposed.