Preemptive treatment with voriconazole in lung transplant recipients

Neoh, Chin Fen; Snell, Gregory I; Levvey, Bronwyn; Kotsimbos, Tom; Morrissey, C. Orla; Slavin, Monica A; Stewart, Kay; Kong, David Chee Ming

doi:10.1111/tid.12071

Cited by 36 publications

(31 citation statements)

References 47 publications

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“…8 It is noted that retrospective cohort studies have supported the use of voriconazole [9][10][11] ; however, no head-to-head trials have been published comparing the efficacy of azole antifungals in this setting. 8 It is noted that retrospective cohort studies have supported the use of voriconazole [9][10][11] ; however, no head-to-head trials have been published comparing the efficacy of azole antifungals in this setting.…”

Section: Introductionmentioning

confidence: 99%

Low dose posaconazole delayed release tablets for fungal prophylaxis in lung transplant recipients

Kozuch

Feist

Yung

et al. 2018

Clinical Transplantation

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In November 2013, posaconazole delayed release (DR) tablets were approved by the FDA with the labeled dose of 300 mg daily for fungal prophylaxis. There are no studies demonstrating the appropriate dose in lung transplant recipients (LTR). We performed a 2-center retrospective cohort study of LTR taking posaconazole DR tablets for prophylaxis between January 2014 and January 2017. Mean serum trough concentrations and percentage of measurements ≥0.7 mcg/mL were compared by daily dose. Forty-nine subjects with 156 steady state serum posaconazole concentrations were included. There was a significant difference in percentage of first measured concentration ≥0.7 mcg/mL by initial daily dose (P = .04). The mean serum posaconazole concentration by dose was 0.9 (±0.42) mcg/mL for 100 mg daily, 1.66 (±0.91) mcg/mL for 200 mg daily, 2.39 (±1.49) mcg/mL for 300 mg daily, and 1.75 (±0.21) mcg/mL for 400 mg daily (P < .001). Mean concentrations were at goal in 63.3%, 96.9%, 94.9%, and 100% of subjects taking 100 mg, 200 mg, 300 mg, and 400 mg daily respectively (P = .04). Our results suggest that doses less than 300 mg daily of posaconazole DR tablets may be adequate to achieve target serum concentrations in LTR. Larger studies are needed to confirm these findings.

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Section: Introductionmentioning

confidence: 99%

Low dose posaconazole delayed release tablets for fungal prophylaxis in lung transplant recipients

Kozuch

Feist

Yung

et al. 2018

Clinical Transplantation

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“…4 Several studies have shown a decreased incidence of fungal infections with antifungal prophylaxis. 5–7 A worldwide survey analyzing the current antifungal prophylactic strategies showed that most transplant centers already use prophylactic antimycotic drugs, with azoles being the preferred agents. 8 …”

Section: Introductionmentioning

confidence: 99%

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Stelzer

Weber²,

Ihle

et al. 2017

Therapeutic Drug Monitoring

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Background:This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intrapatient variability for each azole was determined.Methods:From July 2012 to July 2015, 806 APL of ITR, VOR, posaconazole liquid (POS-Liq), and posaconazole tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation Program. Therapeutic APL were defined as follows: ITR, ≥700 ng/mL; VOR, 1000–5500 ng/mL; and POS, ≥700 ng/mL (prophylaxis) and ≥1000 ng/mL (therapy).Results:VOR and POS-Tab reached the highest number of therapeutic APL, whereas POS-Liq showed the lowest percentage (therapy: ITR 50%, VOR 70%, POS-Liq 38%, and POS-Tab 82%; prophylaxis: ITR 62%, VOR 85%, POS-Liq 49%, and POS-Tab 76%). Risk factors for subtherapeutic APL of all azoles were the azole dose (ITR, P < 0.001; VOR, P = 0.002; POS-Liq, P = 0.006) and age over 60 years (ITR, P = 0.003; VOR, P = 0.002; POS-Liq, P = 0.039; POS-Tab, P < 0.001). Cystic fibrosis was a significant risk factor for subtherapeutic APL for VOR and POS-Tab (VOR, P = 0.002; POS-Tab, P = 0.005). Double lung transplantation (LTx) was significantly associated with less therapeutic APL for VOR and POS-Liq (VOR, P = 0.030; POS-Liq, P < 0.001). Concomitant therapy with 80 mg pantoprazole led to significantly fewer therapeutic POS APL as compared to 40 mg (POS-Liq, P = 0.015; POS-Tab, P < 0.001). VOR displayed the greatest intrapatient variability (46%), whereas POS-Tab showed the lowest (32%).Conclusions:Our study showed that VOR and POS-Tab achieve the highest percentage of therapeutic APL in patients with LTx; POS-Tab showed the lowest intrapatient variability. APL are significantly influenced by azole dose, age, cystic fibrosis, type of LTx, and comedication with proton-pump inhibitors. Considering the high number of subtherapeutic APL, therapeutic drug monitoring should be integrated in the post-LTx management.

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“…Most are retrospective 7,20,22,32-45 and noncomparative. 22,33,34,36,38,39,[42][43][44][45][46][47][48] Of comparative trials, 7,20,[31][32][33]35,37,40,41,45,49,50 all used a nonrandomized, sequential design, with the exception of Drew et al 51 Although the majority of studies evaluated inhaled formulations of amphotericin B alone, 7,22,31,35,47,51 in combination with, 20,40,43 or as compared with other antifungals, 22,36,37,40,51 universal or targeted 20,50 prophylaxis with oral administration of fluconazole, 20,36,40,49 itraconazole, 20,33,34,…”

Section: Efficacy Of Antifungal Prophylaxis Regimensmentioning

confidence: 99%

“…Key published studies evaluating the efficacy of antifungal prophylaxis in lung transplant recipients are summarized in Table 2. 7,15,20,22,31,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]51 Although inhaled formulations of amphotericin B remain the most widely studied agent for antifungal prophylaxis, their optimal dosages, formulations, and durations of therapy remain unknown. [52][53][54] In pharmacokinetic studies performed in lung transplant recipients, inhaled deoxycholate amphotericin B achieves high concentrations in the lower airways of transplanted lungs, but concentrations at the bronchial anastomosis and in native lungs (in the case of single-lung transplant) are lower.…”

Section: Efficacy Of Antifungal Prophylaxis Regimensmentioning

confidence: 99%

“…17,18,20,21 A preemptive approach, defined as the institution of therapy when colonization with Aspergillus is noted, assumes that colonization is the only significant risk factor for infection. 15,40,42,46 A recent meta-analysis pooled the available data regarding the efficacy of antifungal prophylaxis to prevent the development of IA. Overall, there was no significant difference in the rate of IA when pooling three studies that compared universal and no-prophylaxis strategies: 19 of 235 patients (8.1 %) and 28 of 196 patients (14.3 %) developed IA in the universal and no-prophylaxis arms, respectively (relative risk, 0.36; 95% CI, 0.05-2.62).…”

Section: Efficacy Of Antifungal Prophylaxis Regimensmentioning

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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Preemptive treatment with voriconazole in lung transplant recipients

Abstract: Voriconazole preemptive treatment resulted in low incidence of IFI and IFI-related mortality.

Cited by 36 publications

References 47 publications

Low dose posaconazole delayed release tablets for fungal prophylaxis in lung transplant recipients

Low dose posaconazole delayed release tablets for fungal prophylaxis in lung transplant recipients

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

Antifungal Prophylaxis in Lung Transplant Recipients

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