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Background: Disseminated fungal infection is a major cause of morbidity and mortality in children undergoing HCT. Prophylaxis with amphotericin B can be limited by renal toxicity. Oral triazoles can be limited by poor absorption, large interindividual pharmacokinetic (PK) variability, and hepatic toxicity, leading to interruptions in therapy and breakthrough infections. Micafungin has potential advantages, due to its better safety profile, specifically in terms of hepatic and renal toxicity, and lack of drug-drug interactions with common medications used in the HCT setting.
Both animal and adult human data suggest that alternate day dosing schedule can be effective. In a PK study in pediatric HCT patients, we have previously shown detectable and protective Micafungin levels at 48 hours after the dose (Mehta et al, 2010). Here we report our clinical experience of use of alternate day micafungin (3 mg/kg) in high risk pediatric patients undergoing HCT.
Methods: A total of 33 infants and children with various hematological and immune deficiency disorders undergoing HCT were reviewed retrospectively. The median age was 5 years (range 0.5-20). None of the patients had a history of prior fungal infection.
Results: Results are described in Table 1. Eleven patients were started on alternate day Micafungin after sustaining liver dysfunction from voriconazole, liver graft vs. host disease (GVHD), disseminated viral infection and/or veno-occlusive disease. Three patients developed liver dysfunction while on alternate day micafungin from similar causes. In all these patients, continuation of micafungin did not worsen liver dysfunction, which in fact improved in most patients over time. Two patients developed breakthrough fungal infection during alternate day micafungin prophylaxis. One patient had been on micafungin for 8 weeks and another for 14 weeks at the time of developing breakthrough candida line infection and esophagitis respectively. Of note, both these patients had refractory liver and gastrointestinal GVHD and were significantly immunocompromised from multiple immune suppressive therapies for their GVHD.
Conclusion: We conclude that, alternate day micafungin prophylaxis is safe and well tolerated; specifically even in patients with baseline liver dysfunction, without additional liver toxicity. This provides a simple prophylaxis regimen that can be administered for prolonged duration to patients undergoing HCT even on an outpatient basis.
