SEARCHCOHORTpediatrics, critical care

cohort·pediatrics, critical care, infectious disease, clinical trial, pediatric ophthalmology·PMC10051811

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

Pharmaceuticals · 10 authors, 4 centres

AI SUMMARY

FIDELITY 100%

POPULATION53 critically ill neonates and infants with proven or probable systemic candidiasis, including 3 with Candida meningitis

INTERVENTIONIntravenous micafungin at doses ranging from 8 to 15 mg/kg/day for at least 14 days

COMPARISON

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This pooled analysis of 53 neonates and infants with invasive candidiasis evaluated pharmacokinetics of high-dose micafungin (8–15 mg/kg/day).

Full summary

907 CHARS

This pooled analysis combined pharmacokinetic data from 53 neonates and infants with systemic candidiasis, including 3 patients with fungal meningitis and hydrocephalus, treated with intravenous micafungin at 8–15 mg/kg/day. Plasma and CSF concentrations were measured by HPLC. Mean micafungin clearance was higher in neonates before 28 days of life (0.036 L/h/kg) compared to infants after 120 days (0.028 L/h/kg), while half-life was shorter in younger patients (13.5 h vs 14.4 h). CSF measurements in 3 patients demonstrated micafungin crosses the blood–brain barrier at therapeutic concentrations. Microbiological success was 83.3% (95% CI: 51.2–97.9), and all infants clinically recovered. Five patients (9.4%) died, none drug-related. Overall TEAEs occurred in 64.2% of patients, but only 5.7% were drug-related and non-serious (transient hypertransaminasaemia or increased gamma-glutamyltransferase).

PICO

PPOPULATION

53 critically ill neonates and infants with proven or probable systemic candidiasis, including 3 with Candida meningitis

IINTERVENTION

Intravenous micafungin at doses ranging from 8 to 15 mg/kg/day for at least 14 days

OOUTCOME

Plasma and CSF micafungin concentrations, pharmacokinetic parameters (AUC0–24, clearance, half-life), microbiological success, clinical recovery, and treatment-emergent adverse events

STUDY TYPE

cohort

SPECIALTY

pediatrics

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10051811

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

Pharmaceuticals

READ THE FULL PAPER

ABSTRACT

Background : Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods : Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine ® ) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC 0–24 , plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions : The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood–brain barrier reaching therapeutic levels in CSF.

CITATION EXPORT

Domenico Umberto De Rose, Iliana Bersani, Maria Paola Ronchetti et al.. Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies. Pharmaceuticals. (2023). https://doi.org/10.3390/ph16030472

AUTHORS

10 · 4 CENTRES

Domenico Umberto De Rose, Iliana Bersani, Maria Paola Ronchetti, Fiammetta Piersigilli, Sara Cairoli, Andrea Dotta, Amit Desai, Laura Lynn Kovanda, Bianca Maria Goffredo, Cinzia Auriti

1Neonatal Intensive Care Unit, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; [email protected] (I.B.); [email protected] (M.P.R.); [email protected] (A.D.); [email protected] (C.A.)
2Section of Neonatology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
3Biochemistry Laboratory, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; [email protected] (S.C.); [email protected] (B.M.G.)
4Astellas Pharma Global Development Inc., Northbrook, IL 60062, USA; [email protected] (A.D.); [email protected] (L.L.K.)

EDITOR / REVIEWER

Danilo Marimpietri, Guendalina Zuccari