Advances in the Treatment of Mycoses in Pediatric Patients
Abstract
:1. Introduction
- (a)
- Prophylaxis of premature neonates against invasive candidiasis;
- (b)
- management of candidemia and meningoencephalitis in neonates; and
- (c)
- prophylaxis, empiric therapy, and targeted antifungal therapy in children with primary or secondary immunodeficiencies.
2. Prophylaxis of Preterm Babies against Candidiasis
3. Management of Invasive Candidiasis in Neonates
4. Prophylaxis, Empiric Therapy, and Targeted Antifungal Therapy in Children with Primary or Secondary Immunodeficiencies
4.1. Prophylaxis
4.2. Empiric Therapy
4.3. Targeted Therapy
5. Conclusions
Funding
Conflicts of Interest
References
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Drug | Route | Dosage | Indications for Use | References |
---|---|---|---|---|
AMB formulations | ||||
DAMB | IV | • 1 mg/kg/d | • Treatment of IFIs in NICU | [3,4,5] |
• CNS and disseminated cryptococcal disease (combined with 5FC) | [6,7] | |||
LAMB | IV | • 2.5–7 or 3–5 mg/kg/d | • Treatment of IC in neonates | [3,4] |
• No dosage established | • Treatment of HCME in neonates | [8,9] | ||
• 1–3 mg/kg/d | • Empiric fever-driven therapy in hemato-oncological patients at high risk for invasive fungal disease with neutropenia and refractory or new fever of at least 4 days, despite broad-spectrum antibacterial therapy | [10,11] | ||
• 3 mg/kg/d | • Empiric treatment in patients with refractory or new fever episode in the PICU, despite broad-spectrum empirical antibacterial therapy, who are at high risk for Candida infection with moderate-to-severe disease, hemodynamic instability, recent azole exposure, or at high risk for C. glabrata or C. krusei infections | [4,12] | ||
• 3–5 mg/kg/d | • First-line treatment of IFIs (IA, IC) in pediatrics | [3,4,10] | ||
• ≥5 mg/kg | • First-line treatment of mucormycosis | [13,14] | ||
• 5 mg/kg/d | • Candida meningitis and endocarditis (combined with 5FC) | [15] | ||
• 5 mg/kg/d | • Second-line treatment of CNS and disseminated cryptococcal disease (AMB-intolerant patients) | [6,7] | ||
ABLC | IV | • No dosage established | • Treatment of IC in neonates | [16] |
• 5 mg/kg/d | • Treatment of IFIs (IA, IC) in pediatrics | [13] | ||
• 5 mg/kg/d | • Treatment for: Blastomycosis, coccidioidomycosis, histoplasmosis, endemic mycoses | [13,14] | ||
• 5 mg/kg/d | • Second-line treatment of CNS and disseminated cryptococcal disease (AMB-intolerant patients) | [6,7] | ||
Azoles | ||||
FLC | IV, PO | • 3, 4, or 6 mg/kg twice weekly | • Prophylaxis against IC in <1000 gr preterm neonates in NICUs with incidence of IC >10% | [4,17] |
IV | • 25 mg/kg loading dose, followed by 12 mg/kg/d | • Treatment of IC in neonates (according to local epidemiology) | [3,4] | |
PO | • 6–12 mg/kg/d | • Antifungal prophylaxis in high-risk, immunocompromised pediatric patients (not active against molds) | [18,19,20,21,22,23,24] | |
• 6-12 mg/kg/d | • Anti-Candida prophylaxis in patients with primary immunodeficiencies at high risk for IFIs or presenting as chronic fungal infections | [25,26,27,28] | ||
IV, PO | • 10–12 mg/kg/d | • Maintenance treatment of CNS and disseminated cryptococcal disease | [6,7] | |
• 6–12 mg/kg | • Treatment of Cryptococcal pneumonia | [6,7] | ||
• 12 mg/kg/d | • Treatment of IC provided that: It is caused by fluconazole-susceptible organisms, the patient is in stable condition, and has not received prior azole therapy | [3,10,12] | ||
ITC | PO | • 200 mg b.i.d. | • Antifungal prophylaxis in high-risk, immunocompromised pediatric patients (anti-mold activity) | [29,30] |
• 200 mg b.i.d. | • Anti-Aspergillus prophylaxis in patients with primary immunodeficiencies at high risk for IFIs or presenting as chronic fungal infections | [25,26,27,28] | ||
VRC | IV PO | • 8 mg/kg b.i.d. • 9 mg/kg b.i.d. | • Antifungal prophylaxis in pediatric patients with allogeneic HSCT (anti-mold activity) | [10,31] |
IV, PO | • Same as above | • Anti-Aspergillus prophylaxis in patients with primary immunodeficiencies at high risk for IFIs or presenting as chronic fungal infections | [25,26,27,28] | |
IV | • Children 2-11 years: loading 9 mg/kg/dose x 2, followed by maintenance 8 mg/kg/dose x2, with pos 9 mg/kg/dose x2 Children <2 years: higher voriconazole dosages or doses given every 8 h | • First-line therapy for IA | [10,32] | |
IV | • Same as above | • Treatment for: Scedosporiosis, fusariosis (cases of intolerance of or refractoriness to conventional antifungal therapy) | [10,33,34] | |
PSC | PO (susp.) | • 600 mg/d, (given in 3 doses) | • Antifungal prophylaxis for hematological/oncological patients with acute myeloid leukemia, myelodysplastic syndromes, GVHD or in patients undergoing HSCT, in whom a long neutropenic period due to chemotherapy is expected | [12,13,35] |
• 600 mg/d, (given in 3 doses) | • Antifungal prophylaxis in primary immunodeficiencies (including CGD) | [36,37] | ||
• 800 mg/d in 2–4 divided doses | • Treatment for: Scedosporiosis, fusariosis | [10] | ||
• Second line treatment for mucormycosis | [10] | |||
PO (tabl.) | • Children ≥13 years old: 300 mg/d, q.d. Children <13 years: dose not established | • Antifungal prophylaxis in HSCT pediatric patients | [38] | |
• Antifungal prophylaxis in primary immunodeficiencies (including CGD) | [39] | |||
• Treatment for: Scedosporiosis, fusariosis • Second-line treatment for mucormycosis | [10] | |||
ISA | IV | • No dosage established | • PK is being studied in age group 1–18 years | [ClinicalTrials. gov NCT03241550] |
PO | • No dosage established | • PK is being studied in age group 6–18 years | ||
Echinocandins | ||||
MFG | IV | • 4–10 mg/kg/d | • Second-line treatment of IC in neonates | [40,41,42,43] |
• 7–10 mg/kg/d | • Second-line treatment of HCME in neonates | [44,45,46] | ||
Lock Therapy | • Shunt lock therapy in shunt-associated Candida CNS infections (combined with systemic treatment) | [47] | ||
IV | • 2 mg/kg/d | • Antifungal prophylaxis in allogeneic HSCT pediatric patients | [48,49] | |
• 3 mg/kg/d (median dose) | • Alternative treatment choice in pediatric patients with FN | [50] | ||
• 2–4 mg/kg | • Targeted therapy of IC | [3,10] | ||
CAS | IV | • 25 mg/m2, q.d. | • Treatment of IC in neonates and infants <3 months (limited data) | [51,52,53] |
• 50 mg/m2/d | • Antifungal prophylaxis in HSCT pediatric patients | [54,55,56] | ||
• 70 mg/m2/d loading dose, followed by 50 mg/m2/d | • Empiric fever-driven therapy in hemato-oncological patients at high risk for invasive fungal disease with neutropenia and refractory or new fever of at least 4 days, despite broad-spectrum antibacterial therapy | [10,11] | ||
• Same as above | • Second-line therapy of IA • Primary targeted therapy of IC (in Europe) | [3,10] | ||
AFG | IV | • 3 mg/kg loading dose, followed by 1.5 mg/kg/d | • Not yet licensed for patients <18 years | [3,4,10] |
Others | ||||
Nystatin | PO | • 100,000 u (1 mL) | • Second-line choice for antifungal prophylaxis in neonates, in cases of: Fluconazole shortages or resistance | [4] |
Probiotics | PO | • No dosage established | • Prevention of Candida colonization in neonates (unclear efficacy) | [57,58,59,60,61] |
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Iosifidis, E.; Papachristou, S.; Roilides, E. Advances in the Treatment of Mycoses in Pediatric Patients. J. Fungi 2018, 4, 115. https://doi.org/10.3390/jof4040115
Iosifidis E, Papachristou S, Roilides E. Advances in the Treatment of Mycoses in Pediatric Patients. Journal of Fungi. 2018; 4(4):115. https://doi.org/10.3390/jof4040115
Chicago/Turabian StyleIosifidis, Elias, Savvas Papachristou, and Emmanuel Roilides. 2018. "Advances in the Treatment of Mycoses in Pediatric Patients" Journal of Fungi 4, no. 4: 115. https://doi.org/10.3390/jof4040115