Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients

Barg, Assaf Arie; Malkiel, Sarah; Bartuv, Maya; Greenberg, Gahl; Toren, Amos; Keller, Nathan

doi:10.1002/pbc.27281

Cited by 30 publications

(25 citation statements)

References 23 publications

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“…Altogether, pharmacokinetics studies obtained from these patients suggest that a lower dosage of ISAV is not appropriate for the management of paediatric patients. Indeed, higher drug clearance rate and shorter half-life of ISAV in children as compared with adults may explain lower trough levels obtained in these three cases [2]. The final dosage for two paediatric cases was 200 mg/day, the 7-year-old girl received a higher dose increased to 2 × 200 mg/day.…”

Section: Discussionmentioning

confidence: 92%

“…Recently, the use of ISAV in three young children, between 4.5 and 7 years of age having developed mucormycosis, has been reported [2,3]. For two of them, the initial dose of ISAV was lower than that in adult, 80 and 100 mg/ day, respectively.…”

Section: Discussionmentioning

confidence: 95%

“…The use of isavuconazole is approved for the management of invasive aspergillosis and mucormycosis, only in adults, as no paediatric pharmacology studies have been reported to date [1]. Very few paediatric cases have been published concerning the use of isavuconazole [2,3]. Amphotericin B and posaconazole are the only antifungal molecules recommended in mucormycosis in patients with haematological malignancies [4].…”

Section: Introductionmentioning

confidence: 99%

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Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report

Cornu

Bruno

Loridant

et al. 2018

BMC Pharmacol Toxicol

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BackgroundThe use of isavuconazole is approved for the management of invasive aspergillosis and mucormycosis, only in adults, as no paediatric pharmacology studies have been reported to date. Very few paediatric cases have been published concerning the use of isavuconazole. Amphotericin B is the only antifungal agent recommended in paediatric mucormycosis, but adverse effects and especially nephrotoxicity, even with the liposomal formulation, could be problematic. In this context, the use of other antifungal molecules active on Mucorales becomes needful.Case presentationWe describe a case of mucormycosis with rapid onset dissemination in a 3-year-old girl recently diagnosed with acute lymphocytic leukaemia. She was successfully treated with isavuconazole alone and then in combination with liposomal amphotericin B. Isavuconazole therapy was guided by therapeutic drug monitoring.ConclusionsThis case offers new perspectives on the potential use of isavuconazole in children with mucormycosis, as an alternative or adjunct to liposomal amphotericin B.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report

Cornu

Bruno

Loridant

et al. 2018

BMC Pharmacol Toxicol

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“…Four papers described 6 pediatric cases successfully treated with ISA for proven mucormycosis (14)(15)(16)(17). In the studies described in the literature, as summarized in Table 5, ISA was used as a rescue treatment in 4/6 patients, and in two-thirds of the cases, ISA was used as part of combination therapy; most patients also underwent surgical debridement.…”

Section: Discussionmentioning

confidence: 99%

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation

Decembrino

Perruccio

Zecca

et al. 2020

Antimicrob Agents Chemother

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We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

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“…The triazole drug isavuconazole has activity against Mucorales moulds, and a recent single‐arm, open‐label trial in adults showed that isavuconazole had similar all‐cause mortality to LAmB (Marty et al ., ). The safety and efficacy of isavuconazole in paediatric patients have not been established, but isavuconazole has been used successfully to treat mucormycosis in children (Barg et al ., ). A clinical trial is ongoing to determine the optimal delivery of isavuconazole in paediatric patients (ClinicalTrials.gov: NCT 03241550).…”

Section: Treatment Of Ifdmentioning

confidence: 97%

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

Otto

Green

2020

Br J Haematol

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Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.

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Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients

Cited by 30 publications

References 23 publications

Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report

Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

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