Study population
Inclusion criteria
Pediatric patients requiring antifungal prophylaxis after allogeneic
HSCT and bone marrow engraftment.
Patients with toxicity to azoles or amphotericin B requiring a change of
therapy.
Age between 2 months and 18 years.
Informed consent from parents or guardians for all patients and informed
assent for mature minors (over 12 years) following current regulations
(Declaration of Helsinki, Law 14/2007 of July 3 on Biomedical Research).
Exclusion criteria
Severe allergic reaction to micafungin.
Grade 4 toxicity attributable to previous use of micafungin.
Breakthrough IFI during previous use of micafungin.
No informed consent from the patient and/or legal guardian.
Protocol (Figure 1)
1. Micafungin was administered at a dose of 1 mg/kg/day as an antifungal
prophylaxis starting at the onset of the transplant conditioning regimen
and continuing as long as prolonged neutropenia is anticipated.
2. The alternating prophylaxis protocol was initiated after bone marrow
engraftment, that is, when patients present sustained neutrophil counts
≥500 according to the following guidelines:
- In patients weighing <33 kg: 3 mg/kg/dose on Mondays,
Wednesdays and Fridays, with a maximum dose of 100 mg.
-In patients weighing between 33 and 60 kg: 50 mg/dose on Mondays,
Wednesdays and Fridays.
-In patients weighing >60 kg: 100 mg/dose on Mondays,
Wednesdays and Fridays.
The doses were agreed upon with the hospital pharmacy based on existing
data in the literature and the available presentation of the drug. In
children weighing ≤33 kg, agreement was based on existing publications
in pediatrics that suggest maintaining a dose of 3 mg/kg/48 h to
minimize the risks of greater clearance and greater volume of
distribution described in patients with lower weight
(22-24). In patients with a higher weight
and older age, the doses were adjusted to those used in the Adult
Hematology Unit of the center and reported in studies, that is, an
alternating dose of 300 mg/weekly in adults
(26).
Administration is performed on Mondays, Wednesdays and Fridays on an
outpatient basis.
Drug administration schedule
Micafungin (diluted in 0.9% saline solution to a 1 mg/mL standardized
concentration in a horizontal laminar flow booth of the pharmacy
department to garantee its adequate sterility (27)) was administered as
an intravenous infusion for 1 hour, preferably using an infusion pump.
The medication was administered through a Port-a-Cath central line by
expert nurses in the department. The solution should be adequately
protected from light to prevent its degradation.
Alternating prophylaxis was maintained at least until 75 days after
transplantation and was suspended if the patient did not require
immunosuppressants and the CD4 count was >400.
In children with GVHD and/or CD4 ≤400, prophylaxis was maintained until
the resolution of GVHD, the withdrawal of immunosuppression and/or an
increase in the CD4 count.
Serum micafungin levels
Determinations of the valley levels of micafungin were performed in an
alternating schedule. Blood was collected into a 5-mL vacutainer tube
with heparin as an anticoagulant and was protected from light. The
samples were transported under refrigeration to the microbiology
laboratory. The plasma was frozen at -80ºC until analysis. The
concentration of micafungin in human plasma samples was determined by a
high-performance liquid chromatography (HPLC) technique with a linearity
coefficient >0.99 for the entire concentration range
studied, an accuracy of 85-115% and a precision (coefficient of
variation) <20% for the intraday and interday variability,
respectively, and a limit of quantification of 0.5 mg/L (28).