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Systemic antifungal agents used in the treatment of neonatal invasive candidiasis

Systemic antifungal agents used in the treatment of neonatal invasive candidiasis
Drug Clinical uses Dosing Monitoring
First-line agents
Amphotericin B deoxycholate (conventional)
  • First-line agent for initial therapy of neonatal invasive Candida infections in most cases
 1 mg/kg IV every 24 hours
  • Serum electrolytes (including potassium and magnesium) daily or every other day initially; if stable, can space to once or twice weekly
  • Serum Cr daily or every other day initially; if stable, can space to once or twice weekly
  • CBC, twice a week initially; if stable, can space to once a week
  • ALT and AST once after starting treatment; if normal, continue to check once a week
Fluconazole
  • Alternative first-line option for treatment of invasive Candida infections if the isolate is susceptible*
  • Preferred agent for fungal prophylaxis in high-risk neonates

For treatment: 25 mg/kg IV on day 1, followed by 12 mg/kg per dose IV once dailyΔ

For prophylaxis: 6 mg/kg IV or orally twice weekly
  • LFTs twice a week initially; if normal, can space to once a week
  • Monitoring is not necessary for neonates receiving prophylactic fluconazole
Second-line agents
Flucytosine
  • Sometimes used in combination with amphotericin B in neonates with refractory CNS infection
  • Should not be used as monotherapy since resistance can rapidly emerge
  • There is no IV formulation so this agent can only be used in neonates tolerating enteral medications
 25 mg/kg per dose orally every 6 hours
  • Peak and trough serum drug levels
  • CBC every other day initially; if stable, can space to once or twice a week
Lipid complex or liposomal amphotericin B
  • Conventional amphotericin B (deoxycholate) is generally preferred over these formulations in most neonates
  • These agents are reserved for patients who develop intolerant infusion-related reactions or AKI during conventional amphotericin B administration
  • Should not be used in patients with Candida kidney infections
 3 to 5 mg/kg per dose IV once daily
  • Same as for conventional amphotericin B
Micafungin
  • An option for treating invasive Candida infections when neither amphotericin nor fluconazole can be used (eg, due to antifungal resistance and/or drug toxicity)
  • Not appropriate for treating infections involving the eye, CNS, or urinary tract since it has relatively poor penetration at these sites
  • An option for add-on therapy in patients with persistent/refractory infection despite treatment with amphotericin B (uncommon)
 10 mg/kg per dose IV once daily
  • Not necessary in most cases
Caspofungin
  • An option for treating invasive Candida infections when neither amphotericin nor fluconazole can be used (eg, due to antifungal resistance and/or drug toxicity), though data on safety and efficacy are very limited
  • Not appropriate for treating infections involving the eye, CNS, or urinary tract since it has relatively poor penetration at these sites
  • An option for add-on therapy in patients with persistent/refractory infection despite treatment with amphotericin B (uncommon)
 25 mg/m2 per dose IV once daily
  • Not necessary in most cases
This table summarizes guidance for dosing and monitoring of antifungal agents that are used in the treatment of invasive candidiasis in neonates. Infants who are diagnosed with Candida infection involving the bloodstream, urinary tract, CNS, or other site of invasive infection should undergo a thorough evaluation to determine the extent of disease. Antifungal therapy (usually amphotericin B) should be started as soon as possible once Candida has been identified in the blood culture or other specimen. The Candida species and its susceptibility to antifungal agents should be determined, which will guide further management. Consultation with a pediatric infectious disease specialist is appropriate in most cases. For further details, refer to UpToDate topics on Candida infections in neonates.

AKI: acute kidney injury; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CBC: complete blood count; CNS: central nervous system; Cr: creatinine; ELBW: extremely low birth weight; IV: intravenous; LFTs: liver function tests.

* Fluconazole should not be used as the agent for initial treatment of neonatal invasive candidiasis before the isolate's susceptibilities are known due to the potential for fluconazole-resistant Candida species. This is especially important if the neonate previously received fluconazole prophylaxis.

¶ Targeted antifungal prophylaxis is reserved for ELBW infants who are at highest risk of invasive Candida infection. This includes ELBW infants cared for in NICUs with a high baseline rate of systemic fungal infection (ie, >10%) and/or those who require antibiotic therapy for >48 hours (eg, for a confirmed bacterial infection or necrotizing enterocolitis).

Δ IV therapy is preferred over oral therapy for most invasive infections with the exception of simple cystitis, which can be treated with oral fluconazole if the neonate is clinically stable and tolerating feeds. Note that the dosing for fluconazole provided in the table above is for treatment of invasive candidiasis. Fluconazole may also be used to treat superficial mucocutaneous Candida infections (eg, oral thrush that does not respond to topical therapy). Lower dosing is used for treatment of oral thrush (3 to 6 mg/kg per dose given orally once daily for 7 to 14 days).
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