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: April 2, 2014; Last Reviewed: November 6, 2013

Panel's Recommendations for Candida Infections

Panel's Recommendations

  • Uncomplicated oropharyngeal candidiasis (OPC) infection can be effectively treated with topical therapy using clotrimazole troches or nystatin suspension (AII). 
  • Oral fluconazole is recommended for moderate or severe OPC disease (AI*).
  • For fluconazole-refractory OPC, itraconazole oral solution is recommended, although it is less well tolerated than fluconazole (AI).
  • If OPC initially is treated topically, failure or relapse should be treated with oral fluconazole or itraconazole oral solution (AI*).
  • Systemic therapy is essential for esophageal disease (AI*).
  • Oral or intravenous fluconazole, amphotericin B, or an echinocandin (caspofungin, micafungin, anidulafungin), administered for 14 to 21 days, is highly effective for treatment of Candida esophagitis (AI*).
  • For fluconazole-refractory esophageal disease, oral therapy can include itraconazole solution or voriconazole (AIII). 
  • Central venous catheters should always be removed when feasible in HIV-infected children with candidemia (AII).
  • In severely ill children with candidemia, an echinocandin is recommended. In less severely ill children who have not had previous azole therapy, fluconazole is an alternative therapy (AI*). 
  • For patients infected with Candida glabrata or Candida krusei, an echinocandin is recommended (AII*).
  • For patients infected with Candida parapsilosis, fluconazole or amphotericin B is recommended (AII*).
  • Alternatively, an initial course of amphotericin B therapy can be administered for invasive candidiasis and then carefully followed by completion of a course of fluconazole therapy (BIII).
  • Data are insufficient to support routine use of combination antifungal therapy in children with invasive candidiasis (BIII).
  • The potential for drug interactions, particularly with antiretroviral drugs such as protease inhibitors, should be carefully evaluated before initiation of antifungal therapy (AIII).
  • Amphotericin B lipid formulations have a role in children who are intolerant of conventional amphotericin B (deoxycholate) or are at high risk of nephrotoxicity because of preexisting renal disease or use of other nephrotoxic drugs (BII).
  • Children with candidemia should be treated for at least 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 (AII*).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

Dosing Recommendations for Prevention and Treatment of Candidiasis
Preventive Regimen 
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, 3–6 mg/kg body weight daily (maximum 200 mg), 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 (max 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-U 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 HIV-infected children 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 HIV-uninfected immunocompromised children. 

Voriconazole Dosing in Pediatric Patients
  • 9 mg/kg body weight/dose every 12 hours IV loading for day 1, followed by 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 40kg can use adult dosing (load 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 200mg 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).
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

Treatment Duration:
  • Patients with esophageal candidiasis should be treated for a minimum of 3 weeks and for at least 2 weeks following resolution of symptoms.
    • Aged ≥18 years, 400 mg/dose once daily (6 mg/kg body weight once daily).
Treatment Duration:
  • Patients with esophageal candidiasis should be treated for a minimum of 3 weeks and for at least 2 weeks following resolution of symptoms.
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
  • Caspofungin
    • Infants aged <3 months, 25 mg/m2 body surface area/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 based on surface area is recommended for children for caspofungin.
    • 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 bodyweight/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
  • Caspofungin
  • 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.
Not Critically Ill
Fluconazole Recommended
  • 12 mg/kg body weight/dose daily IV(max 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: CD4 = CD4 T lymphocyte; CDC = Centers for Disease Control and Prevention; IV = intravenous; PK = pharmacokinetic

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