title: Intravenous itraconazole against experimental neutropenic Candida parapsilosis infection: efficacy after suppression of bacterial translocation.
abstract: A variety of studies indicate that itraconazole possesses greater intrinsic activity compared to the other azole derivatives against Candida parapsilosis. Efficacy has never been tested in an experimental setting. To this end, C. parapsilosis was used for challenge of 117 rats rendered neutropenic after a course of cyclophosphamide. Rats were assigned to receive intravenous treatment with saline (group A); itraconazole q12h (group B); fluconazole q12h (group C); single dose of ceftriaxone and saline (group D); single dose of ceftriaxone and itraconazole q12h (group E); and single dose of ceftriaxone and fluconazole q12h (group F). Survival was recorded, and yeast outgrowth of liver, spleen, lung, and kidney was measured after sacrifice at serial time intervals. Growth of the test isolate in tissues was significantly lower in group B than in groups A and C after 72 h. However, outgrowth of enterobacteria was found in tissues of groups A, B, and C, implying a phenomenon of bacterial translocation from the gut. When this phenomenon was suppressed with single doses of ceftriaxone, a striking survival benefit of itraconazole-treated animals was found (p = 0.022, group E vs. group F). The present results suggest than in deep infections by C. parapsilosis intravenously administered intraconazole may eradicate the offending agent and provide survival benefit when chemotherapy-induced bacterial translocation from the gut is suppressed. Further clinical evidence is required to support these findings.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Dionyssia-Pinelopi
authors.initials: DP
authors.lastname: Carrer
authors.forename: George
authors.initials: G
authors.lastname: Samonis
authors.forename: Dionyssia-Irini
authors.initials: DI
authors.lastname: Droggiti
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018988:Bacterial Translocation / Q000187:drug effects*; D002175:Candida / Q000187:drug effects* / Q000472:pathogenicity; D002177:Candidiasis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D017964:Itraconazole / Q000494:pharmacology* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D009503:Neutropenia / Q000382:microbiology; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole