From the Guidelines
For pediatric candidiasis not responding to initial treatment, switching to itraconazole or low-dose intravenous amphotericin B is recommended, as up to 80% of patients with fluconazole-refractory infections will respond to itraconazole solution 1.
Treatment Options
- For esophageal disease, itraconazole cyclodextrin oral solution (pediatric dosage: 2.5 mg/kg/dose administered twice a day or 5.0 mg/kg/dose administered once daily for a minimum of 14--21 days) is as efficacious as fluconazole 1.
- Low-dose intravenous amphotericin B (0.3 mg/kg/day for a minimum of 7 days) is also effective and can be used in patients with otherwise refractory disease 1.
Considerations
- Voriconazole has been used in a limited number of children without HIV infection to treat invasive fungal infections, but data are insufficient to recommend its use for esophageal or disseminated candidiasis 1.
- Caspofungin, an echinocandin inhibitor, is effective in adults, but experience is limited in children, and a definitive pediatric dose has not been defined 1.
Recent Guidelines
- The 2009 update by the Infectious Diseases Society of America recommends fluconazole or an echinocandin as initial therapy for most adult patients, with consideration of the patient's severity of illness and recent azole exposure 1.
- For children, the same therapeutic approach is advised, with attention to differences in dosing regimens 1.
Key Points
- Addressing underlying factors is crucial, including managing immunosuppression, discontinuing unnecessary antibiotics, improving glycemic control in diabetic patients, and ensuring good hygiene practices.
- Resistance develops when Candida species alter drug targets or increase efflux pumps to remove antifungals from fungal cells, making medication switching necessary when initial treatments fail.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Treatment of Pediatric Candidiasis
- The treatment of pediatric candidiasis not responding to initial candidiasis treatment is a complex issue, and several studies have investigated this topic 2, 3, 4, 5, 6.
- According to the Infectious Diseases Society of America, early effective antifungal therapy is the key to improved outcomes in pediatric patients with candidemia 2.
- Echinocandins and liposomal amphotericin B (L-AmB) are recommended as first-line agents in the treatment of invasive candidiasis (IC) and candidemia in both immunocompetent and immunocompromised pediatric patients 3.
- Fluconazole or an echinocandin is preferred initial therapy for non-neutropenic candidemia, depending on disease severity and other characteristics 2.
- The guidelines recommend treatment with an echinocandin or lipid formulation of amphotericin B for most patients with neutropenic candidemia, although fluconazole is identified as an alternative for less critically ill patients without recent azole exposure 2.
Antifungal Agents in Neonates
- Four classes of antifungal agents are commonly used in the treatment of fungal infections in pediatric patients: polyene macrolides, fluorinated pyrimidines, triazoles, and echinocandins 4.
- Pharmacokinetic data suggest dosing differences in children versus adult patients with some antifungals, but not all agents have been fully evaluated 4.
- Fluconazole has been used in neonates with invasive candidiasis at dosages of 6 mg/kg/day, and for antifungal prophylaxis in high-risk neonates 4.
- Caspofungin requires higher doses in children relative to adults, and dosing is best accomplished based on body surface area 4.
Updates in Pharmacologic Prophylaxis and Treatment
- Recent studies have validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU, but it remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear 5.
- Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants < 4 months of age 5.
- Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older 5.
- Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population 5.