title: Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS.
abstract: Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.
authors.affiliation: Department of Medicine and Microbiology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Loeb
authors.forename: C
authors.initials: C
authors.lastname: Walach
authors.forename: J
authors.initials: J
authors.lastname: Phillips
authors.forename: I
authors.initials: I
authors.lastname: Fong
authors.forename: I
authors.initials: I
authors.lastname: Salit
authors.forename: A
authors.initials: A
authors.lastname: Rachlis
authors.forename: S
authors.initials: S
authors.lastname: Walmsley
mesh_terms: D000097:Acetonitriles / Q000009:adverse effects / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000818:Animals; D003049:Coccidiostats / Q000009:adverse effects / Q000627:therapeutic use*; D003457:Cryptosporidiosis / Q000188:drug therapy*; D003710:Demography; D003967:Diarrhea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000097:Acetonitriles; D003049:Coccidiostats; D014227:Triazines; C080736:letrazuril