Treatment of Neonatal Aspergillosis
Liposomal amphotericin B is the first-line treatment for neonates with invasive aspergillosis, as voriconazole—the standard first-line agent in older children—is not recommended for use in neonates. 1
Primary Treatment Recommendation
Liposomal amphotericin B (L-AmB) is the drug of choice for neonates with aspergillosis (AIII recommendation), based on the ESCMID-ECMM 2019 guidelines that specifically exclude voriconazole use in this age group 1
Voriconazole, while the standard first-line agent for children ≥2 years with invasive aspergillosis (AIIt), is not approved and not recommended for neonates due to lack of safety and pharmacokinetic data in this population 1
Dosing and Administration
Liposomal amphotericin B dosing: The standard dose for invasive fungal infections in neonates is typically 3-5 mg/kg/day intravenously, though specific neonatal dosing requires individualization based on renal function and clinical response 2, 3
Duration of therapy: Treatment should continue until clinical resolution, radiological improvement, and immune recovery; typically several weeks to months depending on disease severity and extent 1, 3
Alternative and Salvage Options
Caspofungin or other echinocandins may be considered as salvage therapy if amphotericin B fails or is not tolerated, though data in neonates are extremely limited 1, 2
Voriconazole has been used successfully in case reports of extremely low birth weight infants with primary cutaneous aspergillosis refractory to amphotericin B, but this represents off-label use with significant pharmacokinetic uncertainty 4
Combination therapy (amphotericin B plus echinocandin) is not routinely recommended in neonates due to lack of evidence, though it may be considered in refractory cases 1, 5
Critical Management Principles
Prompt initiation of antifungal therapy is essential, as invasive aspergillosis carries high mortality in neonates 1, 3
Source control: Remove or replace central venous catheters if present, as they are major risk factors for invasive fungal infections 3
Environmental assessment: Investigate for environmental sources of Aspergillus exposure, particularly construction or renovation near the neonatal intensive care unit 6
Supportive care: Address underlying prematurity-related conditions and minimize further immunosuppression when possible 1, 3
Important Caveats
Primary cutaneous aspergillosis in neonates (often associated with adhesive tape trauma or IV sites) may have better prognosis than disseminated disease and may respond to shorter courses of amphotericin B therapy 6
Therapeutic drug monitoring is not routinely available for amphotericin B formulations, unlike voriconazole, making clinical and laboratory monitoring of efficacy and toxicity essential 2
Renal function and electrolytes must be monitored closely during amphotericin B therapy, as nephrotoxicity is the primary dose-limiting toxicity even with liposomal formulations 2, 3
Galactomannan testing has limited utility in neonates due to high false-positive rates from bifidobacteria in the neonatal gut microbiome 1