We report a 60-year-old immunocompetent patient with chronic biliary isosporiasis who failed to respond to orally administered cotrimoxazole prophylaxis and orally administered treatment with nitazoxanide, a 5-nitrothiazole benzamide compound. Severe malabsorption was regarded as responsible for the subtherapeutic levels of nitazoxanide in plasma and bile, resulting in treatment failure. Intravenously administered cotrimoxazole stopped the shedding of Isospora belli oocysts in bile within 5 days, excluding initially suspected resistance to cotrimoxazole. Patients with malabsorption and cholangitis due to Coccidia such as Isospora belli and Cryptosporidium spp. or due to protozoa that cause microsporidiasis seem to be predisposed to fail to respond to otherwise effective treatment.