bWe investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 g/ml; P < 0.001) or rifabutin (median, 0.34 g/ml; P < 0.001) than those receiving itraconazole alone (median, 5.92 g/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.
Chronic pulmonary aspergillosis (CPA) is a slowly progressive pulmonary infectious disease secondary to local invasion by a species of Aspergillus, usually Aspergillus fumigatus (1, 2). Although the optimal therapeutic regimen and duration of treatment have not been established, long-term oral itraconazole is currently recommended as the primary treatment for CPA (3-5). CPA usually occurs in middle-aged and elderly patients, for whom the most common underlying disease is pulmonary tuberculosis (6, 7). In addition, there is increasing evidence that nontuberculous mycobacterial (NTM) lung disease is an important underlying condition associated with CPA (7-12), with some patients having CPA and coexisting NTM lung disease (12,13).Mycobacterium avium complex (MAC) is the most common etiology of NTM lung disease (14-16). Rifampin is recommended as part of a multidrug antibiotic regimen for the treatment of MAC lung disease (14-16). Rifampin is a potent inducer of hepatic cytochrome P450 enzymes, which in turn can accelerate the hepatic metabolism of antifungal agents. In this way, rifampin presents a practical challenge for choosing the appropriate antibiotics for treating CPA with coexisting NTM lung disease (17,18). Indeed, previous case reports have demonstrated that concurrent administration of rifampin with itraconazole can greatly reduce serum itraconazole concentrations (19)(20)(21)(22).Rifabutin has less severe drug-drug interactions than does rifampin and is used as a substitute for rifampin in the treatment of tuberculosis and NTM lung disease, especially for patients who are receiving medications that have unacceptable interactions with rifampin, such as antiretroviral agents (14, 23). Nevertheless, there are no published studies that evaluated the interaction between rifabutin and itraconazole. Thus, the objective of the present study was to investigate the effects of rifampin and rifabutin on serum itraconazole levels in patients with CPA and coexisting mycobacterial lung disease.This study was a single-institution retrospective review of 66 patients with CPA who were treated with oral itraconazole (Sporanox, Janssen Pharmaceutica) (200 mg twice daily) and for whom serum itraconazole concentrations were measured between January 2013 and June 2014. Peripheral venous sampling was performed prior to morning itraconazole administration to determine trough concentrations after at least 7 days of treatment.The serum concentrations of itraconazole and hydroxyl-itraconazole we...