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

Cornu, Marjorie; Bruno, Bénédicte; Loridant, Séverine; Navarin, Pauline; François, Nadine; Lanternier, Fanny; Amzallag-Bellenger, Élisa; Dubos, François; Mazingue, Françoise; Sendid, Boualem

doi:10.1186/s40360-018-0273-7

Cited by 24 publications

(19 citation statements)

References 18 publications

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“…All patients but one showed a complete regression of the infection. No adverse events were recorded, except in patient 3, who complained of nausea and vomiting during the first 2 months after ISA initiation (16). No suspension of drug treatment was necessary, and in no case was the scheduled chemotherapy suspended because of ISA interactions.…”

Section: Discussionmentioning

confidence: 94%

“…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%

“…The pharmacokinetic profile of ISA was investigated in three pediatric cases reported by Barg et al (15), Cornu et al (16), and Pomorska et al (17).…”

Section: Discussionmentioning

confidence: 99%

“…The major advantages of ISA in this particular setting of patients are the extended antifungal spectrum of activity, good tolerability and limited drug-to-drug interactions, the possibility to shift from the intravenous to the oral route, and the once-daily frequency of administration. Moreover, it has been reported that an ISA capsule has been opened and its contents dissolved in an acidic beverage or administered via a gastrojejunum tube, in the case of patients with swallowing difficulties (16,24). This could facilitate treatment compliance even in the youngest patients and could be helpful in the setting of a prophylaxis strategy.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetic profile of ISA was investigated in three pediatric cases reported by Barg et al (15), Cornu et al (16), and Pomorska et al (17).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Thus, it may more readily be combined in critically ill patients. Apart from posaconazole, isavuconazole may be another potent option as partner in combination therapy with lipid formulations of amphotericin B in future …”

Section: Combinations Between Antifungalsmentioning

confidence: 99%

Antifungal combinations in Mucorales: A microbiological perspective

Schwarz

Cornely

Dannaoui

2019

Mycoses

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Summary Mucormycosis mostly affects immunocompromised patients and is associated with a high morbidity and mortality despite currently available treatments. In that context, combination therapy might be the key to a better outcome for these patients. Purpose of this review is to summarise and to discuss the current combination data obtained in vitro, in vivo in animal models of mucormycosis, and in patients. In vitro combination studies showed that most of the interactions between antifungal drugs were indifferent, even though that some synergistic interactions were achieved for the combination of echinocandins with either azoles or amphotericin B. Importantly, antagonism was never observed. Animal models of mucormycosis focused on infections caused by Rhizopus arrhizus, neglecting most other species responsible for human disease. In these experimental animal models, no strong interactions have been demonstrated, although a certain degree of synergism has been reported in some instances. Combinations of antifungals with non‐antifungal drugs have also been largely explored in vitro and in animal models and yielded interesting results. In patients with ketoacidosis and rhino‐orbito‐cerebral infection, combination of polyene with caspofungin was effective. In contrast, despite promising experimental data, adjunctive therapy with the iron chelator deferasirox was unfavourable and was associated with a higher mortality than monotherapy with liposomal amphotericin B. More combinations have to be tested in vitro and a much larger panel of Mucorales species has to be tested in vivo to give a valuable statement if antifungal combination therapy could be an effective treatment strategy in patients with mucormycosis.

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