Induction of colitis in hamsters by topical application of antibiotics

Abstract

Syrian hamsters are exquisitely sensitive to clindamycin; as little as 1 mg/kg of clindamycin given systemically causes a fatal colitis. Clindamycin and erythromycin were applied topically daily to the shaved backs of Syrian hamsters in a hydroalcoholic vehicle. A daily dose of 0.1 mg of clindamycin was lethal to more than half the hamsters and 1 mg to all the animals. The antibiotic-associated toxin from Clostridium difficile was present in their cecal material. Based on body surface areas and estimated usual volumes applied, the lethal dose in hamsters is not dissimilar to that given humans for acne. Oral tetracycline therapy protected the animals from clindamycin toxicity, but the animals died three days after stopping tetracycline if topical clindamycin applications were continued.

Clostridium difficile: clinical disease and diagnosis

“…However, viruses have never been propagated from patients with the disease. It has since become apparent, through studies involving animal models and the toxicity of fecal filtrates for cultured mammalian cells, that the major etiology of antibiotic-associated diarrhea and pseudomembranous colitis is C. difficile (17,20,64,74,80,84,131,140,195,206,222).…”

Clostridial typhlitis associated with topical antibiotic therapy in a Syrian hamster

“…Clindamycin applied topically to human skin is absorbed, 48,49 and many human cases of C. difficile pseudomembranous colitis after therapy with topical clindamycin have been reported. 50,51 Feingold et al 52 studied the effects of topically applied clindamycin in hamsters by shaving a dorsal area and bonding a nylon mesh around the treated area to prevent oral ingestion. Clindamycin treatment resulted in deaths within three to seven days, and clostridium toxin was recovered from caecal contents.…”

Topically Administered Clindamycin in the Treatment of Acne Vulgaris and Other Dermatologic Disorders

“…'8 However, traces of clindamycin hydrochloride can be detected in urine, indicating that some absorption does occur.1g, 32 Simple diarrhea has been rarely noted following use of topical ~l i n d a m y c i n .~' In an exquisitely sensitive animal model, a daily topical dose of as little as 0.1 mg may cause PMC. 33 One case of PMC has been reported following topical clindamycin t h e r a~y . 3~ This reaction must be exceedingly uncommon in view of the vast numbers of patients who receive topical clindamycin with no difficulty.…”