title: Epidemiology of invasive fungal infections in lung transplant recipients on long-term azole antifungal prophylaxis.
abstract: Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single-center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15-15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58-4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Pearlie P
authors.initials: PP
authors.lastname: Chong
authors.forename: Cassie C
authors.initials: CC
authors.lastname: Kennedy
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hathcock
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kremers
authors.forename: Raymund R
authors.initials: RR
authors.lastname: Razonable
mesh_terms: D000328:Adult; D019072:Antibiotic Prophylaxis / Q000009:adverse effects*; D000935:Antifungal Agents / Q000009:adverse effects*; D001393:Azoles / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008171:Lung Diseases / Q000150:complications / Q000601:surgery*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D066027:Transplant Recipients; D014481:United States / Q000453:epidemiology
chemical_list: D000935:Antifungal Agents; D001393:Azoles
keywords: antifungal prophylaxis; azole resistance; fungal infections; itraconazole; lung transplantation; therapeutic drug monitoring