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.

Coccidioidomycosis

Last Updated: November 6, 2013; Last Reviewed: November 6, 2013

Panel's Recommendations for Coccidioidomycosis
Panel's Recommendations
  • Routine use of antifungal medications for primary prophylaxis of coccidioidal infections in children is not recommended (BIII).
  • Diffuse pulmonary or disseminated infection (not involving the central nervous system) should be treated initially with amphotericin B (AII*). After completion of amphotericin B, treatment with fluconazole or itraconazole should begin (BIII). Alternatively, some experts initiate therapy with amphotericin B combined with a triazole, such as fluconazole, in patients with disseminated disease and continue the triazole after amphotericin B is stopped (BIII)
  • There is no evidence that lipid preparations of amphotericin are more effective than amphotericin B deoxycholate for the treatment of coccidioidomycosis. Lipid preparations are often preferred because they are better tolerated and associated with less nephrotoxicity than amphotericin B deoxycholate (AII*).
  • For patients with mild disease (e.g., focal pneumonia), monotherapy with fluconazole or itraconazole is appropriate (BII*).
  • Itraconazole is preferred for treatment of skeletal infections (AII*).
  • Because absorption of itraconazole varies from patient to patient, serum concentrations should be measured to ensure effective, non-toxic levels of drug, monitor drug levels following changes in dosage, and assess compliance (BIII).
  • Amphotericin B preparations are not the drugs of choice for treating coccidioidal meningitis; fluconazole is the preferred drug for treating coccidioidal meningitis (AII*)
  • Lifelong antifungal suppression (secondary prophylaxis) with either fluconazole or itraconazole is recommended for treating HIV-infected children after disseminated, diffuse pulmonary, and/or meningeal coccidioidomycosis (AII*), even if immune reconstitution is achieved with combination antiretroviral therapy (cART). Lifelong secondary prophylaxis should be considered for children with mild disease and CD4 T lymphocyte cell count <250 cells/mm3 or <15%, even if immune reconstitution is achieved with cART (BIII).
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 Coccidioidomycosis
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
N/A
N/A
Primary prophylaxis not routinely indicated in children.
Secondary Prophylaxis
Fluconazole 6 mg/kg body weight (maximum 400 mg) by mouth once daily Itraconazole 2–5 mg/kg body weight (maximum 200 mg) by mouth per dose twice daily  Lifelong secondary prophylaxis with fluconazole for patients with meningitis or disseminated disease in the immunocompromised patient is recommended. Secondary prophylaxis should be considered after treatment of milder disease if CD4 count remains <250 cells/mm3 or CD4 percentage <15%.
Treatment Severe Illness with Respiratory Compromise due to Diffuse Pulmonary or Disseminated Non-Meningitic Disease: 
  • Amphotericin B deoxycholate 0.5–1.0 mg/kg body weight IV once daily, until clinical improvement. 
  • A lipid amphotericin B preparation can be substituted at a dose of 5 mg/kg body weight IV once daily (dosage of the lipid preparation can be increased to as much as 10 mg/kg body weight IV once daily for life-threatening infection). 
  • After the patient is stabilized, therapy with an azole (fluconazole or itraconazole) can be substituted and continued to complete a 1-year course of antifungal therapy.
Severe Illness with Respiratory Compromise Due to Diffuse Pulmonary or Disseminated Non-Meningitic Disease (If Unable to Use Amphotericin):
  • Fluconazole 12mg/kg body weight (maximum 800 mg) per dose IV or by mouth once daily
  • Treatment is continued for total of 1 year, followed by secondary prophylaxis.

Surgical debridement of bone, joint, and/or excision of cavitary lung lesions may be helpful.

Itraconazole is the preferred azole for treatment of bone infections.

Some experts initiate an azole during amphotericin B therapy; others defer initiation of the azole until after amphotericin B is stopped. 

For treatment failure, can consider voriconazole, caspofungin, or posaconazole (or combinations). However, experience is limited and definitive pediatric dosages have not been determined.

Options should be discussed with an expert in the treatment of coccidioidomycosis.

Chronic suppressive therapy (secondary prophylaxis) with fluconazole or itraconazole is routinely recommended following initial induction therapy for disseminated disease and is continued lifelong for meningeal disease.

Therapy with amphotericin results In a more rapid clinical response in severe, non-meningeal disease.

Meningeal Infection:
  • Fluconazole 12 mg/kg body weight (maximum 800 mg) IV or by mouth once daily followed by secondary lifelong prophylaxis.
Meningeal Infection (Unresponsive to Fluconazole):
  • IV amphotericin B plus intrathecal amphotericin B followed by secondary prophylaxis. Note: Expert consultation recommended.
Mild-to-Moderate Non-Meningeal Infection (e.g., Focal Pneumonia):
  • Fluconazole 6–12 mg/kg body weight (maximum 400 mg) per dose IV or by mouth once daily.
Mild-to-Moderate Non-Meningeal Infection (e.g., Focal Pneumonia):
  • Itraconazole 2–5 mg/kg body weight per dose (maximum dose 200 mg) per dose IV or by mouth 3 times daily for 3 days, then 2–5 mg/kg body weight (maximum dose 200 mg) by mouth per dose twice daily thereafter. 
  • Duration of treatment determined by rate of clinical response.
Key to Acronyms: CD4 = CD4 T lymphocyte; IV = intravenous

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