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Rationale: Many lung transplant centers prescribe antifungal medications after transplantation to prevent invasive fungal infections (IFIs); however, the effectiveness of antifungal prophylaxis at reducing the risk of all-cause mortality or IFI has not been established. Objectives: We aimed to evaluate the effect of antifungal prophylaxis on all-cause mortality and IFI in lung transplant patients. Methods: Using administrative claims data, we identified adult patients who underwent lung transplantation between January 1, 2005, and December 31, 2018. Propensity score analysis using inverse probability treatment-weighting approach was used to balance the differences in baseline characteristics between those receiving antifungal prophylaxis and those not receiving antifungal prophylaxis. Cox proportional hazards regression was used to compare rates of all-cause mortality and IFI in both groups. Results: We identified 662 lung transplant recipients (LTRs) (387 received prophylaxis and 275 did not). All-cause mortality was significantly lower in those receiving antifungal prophylaxis compared with those not receiving antifungal prophylaxis (event rate per 100 person-years, 8.36 vs. 19.49; hazard ratio, 0.43; 95% confidence interval, 0.26-0.71; P  = 0.003). Patients receiving antifungal prophylaxis had a lower rate of IFI compared with those not receiving prophylaxis (event rate per 100 person-years, 14.94 vs. 22.37; hazard ratio, 0.68; 95% confidence interval, 0.44-1.05; P  = 0.079), but did not reach statistical significance. Conclusions: In this real-world analysis, antifungal prophylaxis in LTRs was associated with reduced all-cause mortality compared with those not receiving antifungal prophylaxis. Rates of IFI were also lower in those receiving prophylaxis, but this was not statistically significant in our primary analysis.

Background: No consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant., Objective: To review data regarding antifungal prophylaxis on the development of fungal infections., Study Selection/appraisal: We searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion., Methods: Of 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term < 6 months and long term ≥ 6 months)., Results: We found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03-17.98; I 2  = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06-13.80; I 2  = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04-0.13; I 2  = 87%) compared to systemic triazoles (0.07, CI: 0.03-0.11; I 2  = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05-0.17; I 2  = 89%; long term: 0.06, CI: 0.03-0.08; I 2  = 51%; P = .39)., Conclusions: We have insufficient evidence to support or exclude a benefit of antifungal prophylaxis., (© 2020 Wiley Periodicals LLC.)

Background: Antifungal prophylaxis strategies for lung transplant recipients vary without consensus or standard of care. Our current study aims to identify antifungal prophylaxis practices in the United States., Methods: From November 29, 2018, to February 15, 2019, we emailed surveys to medical directors of adult lung transplant centers. An alternate physician representative was approached if continued non-response after three survey attempts. Descriptive statistics were used to report findings., Results: Forty-four of 62 (71.0%) eligible centers responded. All Organ Procurement and Transplantation Networks were represented. Only four (9.1%) centers used pre-transplant prophylaxis for prevention of tracheobronchitis (3 of 4) and invasive fungal disease (4 of 4). Thirty-nine of forty (97.5%) centers used post-transplant prophylaxis: 36 (90.0%) universal and 3 (7.5%) pre-emptive/selective prophylaxis. Most centers used nebulized amphotericin with a systemic agent (26 of 36, 72.2%). Thirty-two of thirty-six (88.9%) centers continued universal prophylaxis beyond the hospital setting. Duration of prophylaxis ranged from the post-transplant hospitalization to lifelong with most centers (25 of 36, 69.4%) discontinuing prophylaxis 6 months or less post-transplant., Conclusion: Most United States' lung transplant centers utilize a universal prophylaxis with nebulized amphotericin and a systemic triazole for 6 months or less post-transplant. Very few centers use pre-transplant antifungal prophylaxis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lung transplant recipients are prone to invasive fungal infections prompting many transplant centers to use prolonged triazole antifungal prophylaxis. From a practical standpoint, it is unclear if lung transplant recipients are able to continue prolonged or lifelong prophylaxis without premature discontinuation from side effects, drug interactions, development of fungal disease, or medication cost. We examined the number of patients that are able to reach a prophylactic endpoint and understand the reasons for early termination., Methods: We conducted a retrospective chart review of all lung and heart-lung transplant patients at Mayo Clinic Rochester from May 1, 2002 to December 31, 2017. Type, duration, and reason for discontinuation of triazole prophylaxis were examined., Results: During the study period, 193 patients underwent lung or heart-lung transplantation. Itraconazole, voriconazole, and posaconazole were given to 180, 73, and 60 post-transplant patients, respectively. Providers switched itraconazole to another prophylactic antifungal medication for reasons other than prophylactic completion in 61.8% (126 out of 204) of exposure episodes; this was similar with voriconazole (68.8%, 53 out of 77, P = 0.41). Posaconazole was actively discontinued significantly less often (18.3%, 11 out of 60, P < 0.05). The most common reasons for discontinuing itraconazole were malabsorption (15.5% of exposure episodes) and concern for breakthrough fungal infection (10.2%). In comparison, the most common reason for voriconazole discontinuation was side effect or intolerance (54.5% of VR exposure episodes vs 9.8% of IT exposure episodes, P < 0.05)., Conclusions: Itraconazole and posaconazole appeared to have fewer side effects prompting discontinuation than voriconazole, but itraconazole was discontinued more often because of malabsorption and clinical suspicion of fungal infections., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Infection remains a significant source of morbidity and mortality after lung transplant, including fungal infection. Various antifungal prophylactic agents are administered for a variable duration after transplant with the goal of preventing invasive fungal infections. Alternatively, some programs target the use of antifungal agents only in those colonized with Aspergillus spp. Despite prophylaxis or preemptive therapy, a significant number of invasive fungal infections occur after lung transplant. Risk factors for fungal infections include single lung transplant, pretransplant Aspergillus colonization, environmental risks, structural lung disease such as cystic fibrosis, augmented immunosuppression, sinus disease, and use of indwelling airway stents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)