Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Candida Infections

Last Updated: January 31, 2019; Last Reviewed: January 31, 2019

Panel's Recommendations for Candida Infections

Panel's Recommendations

I. What is the preferred antifungal treatment for oropharyngeal candidiasis (OPC) in children with HIV infection?
  • Uncomplicated OPC infection can be effectively treated with topical therapy using clotrimazole troches or nystatin suspension for 7 to 14 days (strong, moderate).
  • Oral fluconazole for 7 to 14 days is recommended for moderate or severe OPC disease (strong, high).
  • For fluconazole-refractory OPC, itraconazole oral solution is recommended, although itraconazole is less well tolerated than fluconazole (strong, moderate).
  • Chronic suppressive therapy is usually unnecessary; if it is required, fluconazole 3 times weekly is recommended (strong, high).
II. What is the preferred antifungal treatment for esophageal candidiasis in children with HIV infection?
  • Systemic therapy is always required for esophageal disease (strong, moderate).
  • Oral fluconazole is recommended for 14 to 21 days, but amphotericin B or an echinocandin (caspofungin, micafungin, anidulafungin) can be used in patients who cannot tolerate oral therapy (strong, moderate).
  • For refractory esophageal disease, oral therapy can include itraconazole solution or voriconazole for 14 to 21 days (strong, low).
  • Suppressive therapy with fluconazole 3 times weekly is recommended for recurrent infection (strong, moderate).
III. What is the preferred antifungal treatment for invasive candidiasis in children with HIV infection?
  • In moderately severe to severely ill children with invasive candidiasis, an echinocandin is recommended. In less severely ill children who have not had previous azole therapy, fluconazole is recommended (strong, moderate).
  • Alternatively, an initial course of amphotericin B therapy can be administered for invasive candidiasis with careful transition to fluconazole therapy to complete the treatment course (strong, moderate).
  • Amphotericin B lipid formulations have a role in children who are intolerant of conventional amphotericin B (deoxycholate) or who are at high risk of nephrotoxicity because of preexisting renal disease or use of other nephrotoxic drugs (weak, moderate).
  • Children with candidemia should be treated for ≥14 days after documented clearance of Candida from the last positive blood culture and resolution of neutropenia and of clinical signs and symptoms of candidemia (strong, low).
  • Central venous catheters should be removed when feasible in children with candidemia (strong, moderate).

Rating System

Strength of Recommendation: Strong; Weak

Quality of Evidence: High; Moderate; Low; or Very Low

Dosing Recommendations for Prevention and Treatment of Candidiasis
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
Not routinely recommended N/A
N/A
Secondary Prophylaxis
Not routinely recommended but can be considered for frequent severe recurrences.

Fluconazole:
  • Fluconazole 3–6 mg/kg body weight daily (maximum 200 mg) by mouth, or itraconazole oral solution, 2.5 mg/kg body weight/dose twice daily
N/A Secondary Prophylaxis Indicated:
  • Frequent or severe recurrences
Criteria for Discontinuing Secondary Prophylaxis:
  • When CD4 count or percentage has risen to CDC immunologic Category 2 or 1
Criteria for Restarting Secondary Prophylaxis:
  • Frequent severe recurrences
Treatment
Oropharyngeal:
  • Fluconazole 6–12 mg/kg body weight (maximum 400 mg/dose) by mouth once daily
  • Clotrimazole troches, 10-mg troche by mouth 4–5 times daily
  • Nystatin suspension 4–6 mL by mouth 4 times daily, or 1–2, 200,000-unit flavored pastilles by mouth 4–5 times daily
Treatment Duration:
  • 7 to 14 days
Oropharyngeal (Fluconazole-Refractory):
  • Itraconazole oral solution 2.5 mg/kg body weight/dose by mouth twice daily (maximum 200–400 mg/day)
Itraconazole oral solution should not be used interchangeably with itraconazole capsules. Itraconazole capsules are generally ineffective for treatment of esophageal disease.

Central venous catheters should be removed, when feasible, in children with HIV with fungemia.

In uncomplicated catheter-associated C. albicans candidemia, an initial course of amphotericin B followed by fluconazole to complete treatment can be used (use invasive disease dosing).

Voriconazole has been used to treat esophageal candidiasis in a small number of immunocompromised children without HIV.

Voriconazole Dosing in Pediatric Patients:
  • Voriconazole 9 mg/kg body weight/dose every 12 hours IV loading for day 1, followed by voriconazole 8 mg/kg body weight/dose IV every 12 hours.
  • Conversion to oral voriconazole should be at 9 mg/kg body weight/dose orally every 12 hours.
  • Children aged ≥12 years and weighing at least 40 kg can use adult dosing (load voriconazole 6 mg/kg body weight/dose every 12 hours IV on day 1, followed by 4 mg/kg body weight/dose every 12 hours IV. Conversion to oral therapy at 200 mg every 12 hours by mouth).
Anidulafungin in Children Aged 2–17 Years:
  • Loading dose of 3 mg/kg body weight/once daily followed by 1.5 mg/kg body weight/once daily (100 mg/day maximum).
Fluconazole Dosing Considerations:
  • If a neonate’s creatinine level is >1.2 mg/dL for >3 consecutive doses, the dosing interval for fluconazole 12 mg/kg body weight may be prolonged to one dose every 48 hours until the serum creatinine level is <1.2 mg/dL.
  • Aged ≥18 Years: 400 mg/dose once daily (6 mg/kg body weight once daily).
Esophageal Disease:
  • Fluconazole 6–12 mg/kg body weight by mouth once daily (maximum dose: 600 mg)
  • Itraconazole oral solution, 2.5 mg/kg body weight/dose by mouth twice daily
Treatment Duration:
  • Minimum of 3 weeks and for at least 2 weeks following the resolution of symptoms
Esophageal Disease::
  • Amphotericin B (deoxycholate) 0.3–0.7 g/kg body weight IV once daily
Echinocandins
Anidulafungin:
  • Aged 2–17 Years: Loading dose of 3 mg/kg body weight/daily and then maintenance at 1.5 mg/kg body weight/dose daily IV
  • Aged ≥18 Years: 200-mg loading dose, then 100 mg/dose daily IV
Caspofungin:
  • Infants Aged <3 Months: 25 mg/m2 BSA/dose daily IV
  • Aged 3 Months–17 Years: 70 mg/m2/day IV loading dose followed by 50 mg/m2/day IV (maximum 70 mg). Note: Dosing of caspofungin for children should be based on body surface area.
  • Aged ≥18 Years: 70-mg loading dose IV, then 50 mg/dose daily IV
Micafungin:
  • Note: In the United States, optimal dosing for children is not yet established, and there is no pediatric indication yet. Studies indicate linear PK; age and clearance are inversely related (see recommended doses below).
  • Neonates: Up to 10–12 mg/kg body weight/dose daily IV may be required to achieve therapeutic concentrations.
  • Infants <15 kg body weight, 5–7 mg/kg body weight/dose daily IV
  • Children ≤40 kg body weight and aged 2–8 years, 3–4 mg/kg body weight/dose daily IV
  • Children ≤40 kg body weight and aged 9–17 years, 2–3 mg/kg body weight/dose daily IV
  • Children >40 kg body weight, 100 mg/dose daily IV
IV Fluconazole:
  • Children: 6–12 mg/kg body weight/dose daily for infants and children of all ages (maximum dose: 600 mg daily).
Invasive Disease
Critically ill
Echinocandin Recommended
Anidulafungin:
  • Aged 2–17 Years: Load with 3 mg/kg body weight/daily dose IV and then maintenance dose at 1.5 mg/kg body weight once daily
  • Aged ≥18 Years: 200-mg loading dose, then 100 mg once daily
Caspofungin:
  • Infants Aged <3 Months: 25 mg/m2 BSA/dose once daily IV
  • Aged 3 months–17 years, 70 mg/m2 BSA/day loading dose followed by 50 mg/m2 once daily (maximum 70 mg). Note: Dosing of caspofungin in children should be based on body surface area.
  • Aged ≥18 Years: 70-mg loading dose, then 50 mg once daily
Micafungin:
  • Note: In the United States, optimal dosing for children is not yet established, and there is no pediatric indication yet. Studies indicate linear PK; age and clearance are inversely related (see recommended doses below).
  • Neonates: Up to 10–12 mg/kg body weight/dose daily IV may be required to achieve therapeutic concentrations.
  • Infants <15 kg body weight: 5–7 mg/kg/day
  • Children ≤40 kg body weight and aged 2–8 years: 3–4 mg/kg body weight/dose daily IV
  • Children ≤40 kg body weight and aged 9–17 years: 2–3 mg/kg body weight/dose daily
  • Children >40 kg body weight: 100 mg/dose daily IV
Treatment Duration:
  • Based on presence of deep-tissue foci and clinical response; in patients with candidemia, treat until 2 weeks after last positive blood culture.
Not critically ill
Fluconazole Recommended:
  • 12 mg/kg body weight/dose daily IV (maximum dose: 600 mg) for infants and children of all ages
  • Avoid fluconazole for C. krusei and C. glabrata, avoid echinocandin for C. parapsilosis.
Treatment Duration:
  • Based on presence of deep-tissue foci and clinical response; in patients with candidemia, treat until 2 weeks after last positive blood culture.
Invasive Disease:
  • Fluconazole 12 mg/kg body weight IV once daily (maximum 600 mg/day) for minimum 2 weeks after last positive blood culture (if uncomplicated candidemia)
  • Lipid formulations of amphotericin B, 5 mg/kg body weight IV once daily
  • Amphotericin B deoxycholate, 1 mg/kg body weight IV once daily
Key to Abbreviations: BSA = body surface area; CD4 = CD4 T lymphocyte; CDC = Centers for Disease Control and Prevention; IV = intravenous; PK = pharmacokinetic

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