What is the diagnosis and treatment for Candidiasis in infants (neonates)?

From the Guidelines

For the diagnosis and treatment of Candidiasis in infants (neonates), I strongly recommend using AmB deoxycholate, 1 mg/kg daily, or fluconazole, 12 mg/kg intravenous or oral daily, as the primary treatment options, with a strong emphasis on removing or replacing central venous catheters (CVCs) to prevent prolonged infection and neurodevelopmental impairment. The diagnosis of Candidiasis in neonates can be challenging due to nonspecific symptoms, and it is essential to consider the risk factors, such as prematurity and low birth weight, when evaluating these patients 1. The treatment options for neonatal candidiasis include:

• AmB deoxycholate, 1 mg/kg daily, which is recommended for neonates with disseminated candidiasis 1
• Fluconazole, 12 mg/kg intravenous or oral daily, which is a reasonable alternative in patients who have not been on fluconazole prophylaxis 1
• Lipid formulation AmB, 3–5 mg/kg daily, which can be used with caution, particularly in the presence of urinary tract involvement 1
• Echinocandins, which should be used with caution and generally limited to salvage therapy or situations where resistance or toxicity preclude the use of AmB deoxycholate or fluconazole 1 It is also crucial to perform a lumbar puncture and a dilated retinal examination in neonates with cultures positive for Candida species from blood and/or urine, as well as computed tomographic or ultrasound imaging of the genitourinary tract, liver, and spleen if blood cultures are persistently positive for Candida species 1. In addition to these diagnostic and treatment measures, removing or replacing CVCs is strongly recommended to prevent prolonged infection and neurodevelopmental impairment 1. Prophylaxis with fluconazole, 3–6 mg/kg twice weekly, may be considered in nurseries with high rates of invasive candidiasis, particularly in neonates with birth weights <1000 g 1. Overall, the management of Candidiasis in neonates requires a comprehensive approach that includes prompt diagnosis, effective treatment, and preventive measures to minimize the risk of complications and improve outcomes.

From the FDA Drug Label

Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available Oropharyngeal candidiasis: The recommended dosage of fluconazole tablets for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse Esophageal candidiasis: For the treatment of esophageal candidiasis, the recommended dosage of fluconazole tablets in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms. Systemic Candida infections: For the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children

The diagnosis of candidiasis in infants (neonates) is not explicitly stated in the provided drug labels. The treatment for candidiasis in infants (neonates) with fluconazole is as follows:

• Oropharyngeal candidiasis: 6 mg/kg on the first day, followed by 3 mg/kg once daily for at least 2 weeks
• Esophageal candidiasis: 6 mg/kg on the first day, followed by 3 mg/kg once daily for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms
• Systemic Candida infections: daily doses of 6 to 12 mg/kg/day Note that experience with fluconazole in neonates is limited, and the dosage should be administered every 72 hours in the first two weeks of life, and once daily after that 2.

From the Research

Diagnosis of Candidiasis in Infants (Neonates)

• Candidiasis in neonates is a common infection that occurs often during the first few months after birth 3
• The diagnosis of candidiasis in neonates is crucial to prevent further dissemination and potential fatal outcomes 4
• Infection with Candida species is associated with significant morbidity and mortality in infants, and early diagnosis is critical for improved outcomes 5

Treatment of Candidiasis in Infants (Neonates)

• Treatment modalities for oral candidosis in neonates include non-absorbable drugs such as nystatin and miconazole, and systemically active agents such as clotrimazole, ketoconazole, itraconazole, and fluconazole 3
• Echinocandins and liposomal amphotericin B (L-AmB) are the first-line agents in the treatment of invasive candidiasis/candidemia in pediatric and neonatal patients 4
• Fluconazole, amphotericin B deoxycholate, and micafungin are appropriate antifungal agents for the treatment of Candida infections in neonates 5
• Prophylactic antifungal therapy, such as fluconazole, has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants 6

Antifungal Pharmacotherapy for Neonatal Candidiasis

• New antifungals have been developed in the past decade, and some clinical experience has been reported to guide the treatment of infants with serious Candida infections 7
• The choice of antifungal agent depends on the severity of the infection, the patient's underlying conditions, and the potential risk of dissemination 3, 4
• Empiric antifungal therapy may lower mortality and improve outcomes in high-risk neonates 6