Voriconazole in the Treatment of Invasive Aspergillosis in Kidney Transplant Recipients

Veroux, Massimiliano; Corona, Daniela; Gagliano, M.; Sorbello, Massimiliano; Macarone, M.; Cutuli, M.; Giuffrida, G; Morello, Gianluigi; Paratore, A.

doi:10.1016/j.transproceed.2007.05.012

Cited by 32 publications

(20 citation statements)

References 16 publications

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“…In 2 small retrospective studies of 4 and 8 patients with fungal infections, graft loss was observed in 25% to 30% of the patients. 10,16 We found that the graft prognosis was significantly poorer in the patients with IA compared to the controls. Graft loss was attributed to transplant glomerulopathy in all cases of IA, but no biopsies were performed in these patients.…”

Section: Discussionmentioning

confidence: 68%

“…3,4 However, the 12-week mortality rate was lower than that reported in other studies of patients receiving voriconazole (ie, 6% in our study compared to 19% in the recent study of Heylen et al 6 and 34.4% among SOT recipients. 7 Similarly, in the Veroux et al 10 study, none of 4 patients receiving voriconazole died within 13 months after IA. Improved diagnostic methods, including a galactomannan assay, 15 the use of quantitative Aspergillus PCR and the isolation of Aspergillus species, may also shorten the time to diagnosis and treatment initiation, thereby improving survival rates.…”

Section: Discussionmentioning

confidence: 89%

“…From 2003 to 2013, 16 patients developed IA in our cohort of 2000 KTR, which is consistent with previous results. 3,10 Thus, despite an increase in transplants among elderly and highly immunized patients, no IA breakthrough was observed. Although early IA was described in half of the IA cases in solid organ transplantation (SOT) 10 years ago, 3,11 our study, in accordance with other recent studies, 4,6 demonstrated that late IA (>6 months after transplantation) is more frequent in KTR, occurring in 69% of patients.…”

Section: Discussionmentioning

confidence: 99%

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Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study

Poirée

Snanoudj

Bougnoux

et al. 2016

Transplantation Direct

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BackgroundInvasive aspergillosis (IA) is a major cause of invasive fungal infection in kidney transplant recipients (KTR), and it has a high mortality rate. However, its impact on patients and graft survival has not been well defined in the current era of voriconazole first-line therapy.MethodsWe retrospectively collected all cases of KTR-associated IA occurring at Necker Enfants Malades Hospital, Paris, from 2003 to 2013. These cases were compared with a group of controls (1:3) who were matched by age, year of kidney transplantation, and sex. The characteristics of IA were also studied.ResultsSixteen patients developed IA after KTR. Most IA cases were limited to the lungs (81.3%), with mild respiratory symptoms in only 53% of the patients. The patients were administered voriconazole (n = 15, 94%) and/or posaconazole (n = 2, 13%). The 12-week and 1-year postinfection survival rates were 94% and 81%, respectively. Compared with the controls (n = 46), patients and death-censored graft survivals rates were significantly lower after IA (P = 0.017 and 0.001, respectively). In the patients with IA, the occurrences of cardiovascular diseases before transplantation (P < 0.0001), delayed graft function (P < 0.0001), and infectious complications (0.0018) were significantly more frequent.ConclusionsEven with voriconazole therapy, the prognosis of patients with IA after kidney transplantation is still poor. When the patients survive to IA, they have a high risk of graft loss.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study

Poirée

Snanoudj

Bougnoux

et al. 2016

Transplantation Direct

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“…Furthermore, use of voriconazole has yielded better results regarding responses, safety, and survival rates 20 and is highly effective in invasive aspergillosis in KT recipients. 21 The oral voriconazole formulation can be used safely without dosage adjustments in cases with renal impairment. However, intravenous voriconazole formulation contains excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin), which may accumulate in renal insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2014

Exp Clin Transplant

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Objectives: Fungal infections represent 5% of infections in renal transplant recipients. Candidiasis is the most frequent, followed by aspergillosis and cryptococcosis. Invasive aspergillosis is severe and has a poor prognosis, but recent series focused on outcomes are scarce in the literature. We analyzed invasive aspergillosis cases in a cohort of kidney transplant recipients and suggest that prognosis is improved with early diagnosis and treatment. Patients and Methods: A retrospective study was performed in all kidney transplant undertaken in our hospital from January 1979 to December 2012. The incidence and characteristics of invasive aspergillosis were collected from kidney transplant prospective registry and microbiology laboratory. Results: We found 7 invasive aspergillosis cases (6 probable invasive aspergillosis and 1 possible invasive aspergillosis, according to EORTC/IFICG criteria); cumulative incidence 0.78% (7/891). The median posttransplant time until the disease onset was 3.03 months (interquartile range, 2.4-3.2 months), with a mean age of 56 years at the time of diagnosis. Six patients were male. Four patients had previous pulmonary disease. Six patients had received induction therapy (5 anti-IL2R antibodies, 1 with antilymphocytic antibodies). Two patients had received extra immunosuppression (1 with thymoglobulin to treat an acute rejection and the other 1 had a lymphoproliferative disorder and was on chemotherapy). Six patients were on calcineurin inhibitors at the time of diagnosis. Aspergillus fumigatus was the specimen most commonly isolated (6 cases). Six patients had a bacterial coinfection and 1 had a cytomegalovirus coinfection. All patients were treated with antifungal agents; 3 of which received voriconazole. Four patients satisfactorily resolved the episode and 3 died. Conclusions: Invasive aspergillosis incidence is low in kidney transplant although potentially lethal. We observed an acceptable survival of patients analyzed, better than usually reported. A high index of suspicion is essential to get an early diagnosis and start treatment.

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“…24 Smaller observational studies and case reports have also demonstrated the efficacy of voriconazole for treatment of invasive aspergillosis in specific populations of immunocompromised patients. 41,42 The only literature to date that has investigated the role of voriconazole for treatment of invasive aspergillosis in patients without immunocompromise was a retrospective trial involving patients with chronic necrotizing pulmonary aspergillosis. 43 In that study, 58% of the patients had a response to voriconazole by the end of follow-up, after a median duration of treatment of 9 months.…”

Section: Aspergillosismentioning

confidence: 99%

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Kuo

Ensom

2009

CJHP

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Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective:To determine the utility of therapeutic drug monitoring for voriconazole. Methods:A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug-drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug-drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions:Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility. Méthodes : Un algorithme de prise de décision publié a été utilisé pour évaluer la documentation actuellement disponible sur le suivi thérapeutique pharmacologique du voriconazole. Résultats :Plusieurs méthodes analytiques peuvent servir à quantifier les concentrations sériques ou plasmatiques de voriconazole. Les raisons de recourir au suivi thérapeutique pharmacologique de ce médicament sont notamment la grande variabilité intra et interindividuelle attribuable aux propriétés du médicament, aux interactions médicament-médicament et aux affections. De plus, le voriconazole a un comportement pharmacocinétique non linéaire en raison d'une clairance hépatique saturable. Un autre facteur potentiellement en faveur du suivi thérapeutique pharmacologique du voriconazole est le polymorphisme génétique du CYP2C19 qui, chez les patients homozygotes ayant un faible métabolisme (environ 19 % des Asiatiques ...

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Voriconazole in the Treatment of Invasive Aspergillosis in Kidney Transplant Recipients

Cited by 32 publications

References 16 publications

Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study

Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study

Untitled

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

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