title: Breakthrough Candida infections in patients receiving voriconazole.
abstract: OBJECTIVE
  To describe 2 instances of breakthrough Candida infection in 2 patients on treatment doses of voriconazole.
  
  
  METHODS
  A 27-year-old woman with systemic lupus erythematosus was receiving high-dose voriconazole (400 mg twice daily) for central nervous system lesions of unknown origin and developed oral thrush. The patient was receiving concomitant therapy with phenytoin 400 mg/day. The voriconazole dose was increased to 400 mg 3 times daily, and the thrush resolved. A 50-year-old man with HIV infection was receiving enfuvirtide, lamivudine, tenofovir, and efavirenz 600 mg/day, as well as prophylactic trimethoprim/sulfamethoxazole and azithromycin. He was started on voriconazole 200 mg twice daily for pulmonary aspergillosis and developed esophageal candidiasis. The voriconazole dose was increased to 350 mg twice daily, and the thrush eventually resolved.
  
  
  CONCLUSIONS
  Both reactions were probable according to the Naranjo probability scale. Significant drug interactions may have played a role in the development of breakthrough infections in these patients, specifically with phenytoin and efavirenz. Voriconazole is metabolized primarily by CYP2C19, as well as CYP2C9 and CYP3A4. Voriconazole is also known to inhibit these enzymes, and the manufacturer reports an extensive list of drugs that interact with voriconazole.
  
  
  CONCLUSIONS
  Although requiring systematic evaluation, there may be a role for voriconazole serum concentration monitoring to ensure therapeutic efficacy when significant drug interactions are suspected.
authors.affiliation: Pharmacy Department, Northwestern Memorial Hospital, Chicago, IL, USA. lgerzens@nmh.org
authors.forename: Lana
authors.initials: L
authors.lastname: Gerzenshtein
authors.forename: Shilpa M
authors.initials: SM
authors.lastname: Patel
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Postelnick
authors.forename: John P
authors.initials: JP
authors.lastname: Flaherty
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents; D000927:Anticonvulsants / Q000009:adverse effects; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects; D011743:Pyrimidines / Q000627:therapeutic use*; D017211:Treatment Failure; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D019380:Anti-HIV Agents; D000927:Anticonvulsants; D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D010672:Phenytoin; D065819:Voriconazole