title: Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with chronic granulomatous disease successfully treated with long-term oral posaconazole and surgery.
abstract: We describe a patient with chronic granulomatous disease and proven Aspergillus fumigatus osteomyelitis of the midfoot, while receiving itraconazole-prophylaxis. The isolate proved resistant to itraconazole as well as voriconazole, and showed reduced susceptibility to posaconazole. Although molecular analysis demonstrated the presence of a 53 base pair tandem repeat in the promoter region for cyp51A, i.e., the gene coding for the target enzyme of the azole antifungals, there were no mutations in the cyp51A gene. Since transformation of the promoter region into wild-type strains did not result in an azole resistant phenotype, a yet unknown mutation was suspected. The patient was treated with extensive surgery and two weeks of caspofungin therapy, followed by one year of posaconazole therapy. He made a complete recovery and did not experience any side effects. Long-term posaconazole proved to be a safe and effective treatment for multi-azole resistant A. fumigatus osteomyelitis in this immunocompromised patient.
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Amsterdam. C.J.Hodiamont@amc.uva.nl
authors.forename: Caspar J
authors.initials: CJ
authors.lastname: Hodiamont
authors.forename: Koert M
authors.initials: KM
authors.lastname: Dolman
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: Ten Berge
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001228:Aspergillosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000382:microbiology / Q000601:surgery; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001393:Azoles / Q000494:pharmacology / Q000627:therapeutic use; D025141:Drug Resistance, Fungal; D005529:Foot Bones / Q000000981:diagnostic imaging; D006105:Granulomatous Disease, Chronic / Q000150:complications*; D006801:Humans; D008297:Male; D010019:Osteomyelitis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000382:microbiology / Q000601:surgery; D011859:Radiography; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D014230:Triazoles; C101425:posaconazole