Practice variation in <i>Aspergillus</i> prophylaxis and treatment among lung transplant centers: a national survey

He, Songjie; Makhzoumi, Zaineb; Singer, Jonathan P.; Chin‐Hong, Peter; Arron, Sarah T.

doi:10.1111/tid.12337

Cited by 30 publications

(36 citation statements)

References 24 publications

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“…In worldwide surveys conducted among lung transplant centers, only 31% to 36% of centers perform preemptive therapy — a strategy of providing antifungal therapy only on detection of fungal infection by surveillance cultures or fungal antigen detection in clinical specimens. 17–19 Studies have shown that detection of Aspergillus spp on surveillance cultures during the first 3 months after lung transplantation is a good marker for initiation of preemptive therapy. 20 This preemptive strategy is based on the principle of providing antifungal drugs only to the population at highest risk of invasive fungal disease.…”

Section: Preventionmentioning

confidence: 99%

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Fungal Infections After Lung Transplantation

Kennedy

Razonable

2017

Clinics in Chest Medicine

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Section: Preventionmentioning

confidence: 99%

“…17–19 There is wide variation, however, in this practice — that is, whether this is given to all lung transplant recipients (universal approach) or only to selected patients (targeted approach) is subject to debate. Likewise, there is no consensus on the choice of antifungal agent, route of administration, and duration of prophylaxis.…”

Section: Preventionmentioning

confidence: 99%

Fungal Infections After Lung Transplantation

Kennedy

Razonable

2017

Clinics in Chest Medicine

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“…Nevertheless, 2 recent surveys noted that some centers are using posaconazole (as monotherapy or in combination with inhaled lipid amphotericin B), both within and after the first 6 months posttransplantation, in patients intolerant to voriconazole. 6,9,40,75 Limited data are available to evaluate the prophylactic use of echinocandins in lung transplant recipients, although 2 recent surveys note its use as first-line prophylaxis in some centers, as monotherapy or in combination with intravenous lipid amphotericin B. 6,9 A prospective study evaluated the pharmacokinetics and pharmacodynamics of intravenous micafungin in this patient population.…”

Section: Future Directionsmentioning

confidence: 99%

“…use preemptive or targeted (to high risk) therapy, usually based on preoperative (for CF patients) or postoperative colonization with Aspergillus spp. 6,9 Therapeutic drug monitoring of itraconazole and voriconazole is currently used in 26% of adult and 86% of adult and pediatric centers, respectively. 9,60 In pediatric lung transplant centers, the most commonly used regimens are monotherapy with either voriconazole or inhaled amphotericin, with alternative antifungals generally reserved for patients who are intolerant, or who experience toxicity or positive surveillance cultures.…”

Section: Efficacy Of Antifungal Prophylaxis Regimensmentioning

confidence: 99%

“…5 Lung transplant recipients are at exceptionally high risk for developing fungal infections, with a reported cumulative incidence of IFIs of 8.6% in the first year after lung or heart-lung transplantation, despite the use of prophylactic regimens at most institutions. 3,6 The most common cause of infection is Aspergillus spp, with an incidence as high as 40.5 cases per 1 000 patient-years. 7 Recent analysis of surveillance data confirms the predominance of Aspergillus spp.…”

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confidence: 99%

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Antifungal Prophylaxis in Lung Transplant Recipients

Patel

Eschenauer²,

Stuckey³

et al. 2016

Transplantation

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Invasive fungal infection remains a serious postoperative complication in lung transplant recipients and is associated with significant morbidity and mortality. Although most lung transplant centers use antifungal prophylaxis, consensus on the strategy, choice of antifungal agent(s), route of administration, and duration of prophylaxis have not been established. This review provides an overview of the epidemiology and risk factors for common fungal infections seen in lung transplant recipients, evaluates the clinical efficacy and toxicity of the various antifungal agents used to prevent infection, and offers recommendations and opportunities for future research. Currently available data evaluating the efficacy of antifungal prophylaxis strategies is limited by a lack of prospective, randomized clinical trial data and variability in patient populations, prophylactic and immunosuppressive strategies, dosing, durations of use of antifungal agents, and definitions of invasive infection. There is controversy regarding significant risk factors for invasive fungal infection, which has limited the development and validation of targeted prophylactic strategies. Inhaled formulations of amphotericin B remain the most widely studied option for universal prophylaxis and have been shown to be effective in reducing the incidence of invasive Aspergillosis as compared with no prophylaxis. Concern over early postoperative extrapulmonary infection may suggest a benefit of initial prophylaxis with a systemic azole. Long-term use of systemic antifungals is not optimal due to emerging evidence of long-term toxicities. Multicenter, randomized trials are needed to ascertain the optimal prophylactic strategy in lung transplant recipients. New agents and delivery mechanisms may offer additional opportunities for comparative research.

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Voriconazole and the Risk of Keratinocyte Carcinomas Among Lung Transplant Recipients in the United States

et al. 2020

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IMPORTANCEThe antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). OBJECTIVE To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019.EXPOSURES Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. MAIN OUTCOMES AND MEASURESPrimary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. RESULTS Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). CONCLUSIONS AND RELEVANCEIn this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

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Practice variation in Aspergillus prophylaxis and treatment among lung transplant centers: a national survey

Cited by 30 publications

References 24 publications

Fungal Infections After Lung Transplantation

Fungal Infections After Lung Transplantation

Antifungal Prophylaxis in Lung Transplant Recipients

Voriconazole and the Risk of Keratinocyte Carcinomas Among Lung Transplant Recipients in the United States

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