Table 3. Treatment of Opportunistic Infections in Children with and Exposed to HIV — Summary of Recommendations

• Ceftriaxone 50–100 mg/kg body weight per dose once daily, or 25–50 mg/kg body weight per dose twice daily IV or IM (max 4 g/day), or
• Cefotaxime 40–50 mg/kg body weight per dose 4 times daily, or 50–65 mg/kg body weight 3 times daily (max 8–10 g/day) IV

• Cefuroxime, 35–50 mg/kg body weight per dose 3 times daily (max 4–6 g/day) IV

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 infants younger than 4 months is not yet established. 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 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 infants younger than 4 months is not yet established. 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 the presence of deep-tissue foci and clinical response, in patients with candidemia, treat until 2 weeks after the 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

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.

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. 

Non-hospitalized Children at High Risk of Progression to Severe COVID-19

Aged ≥28 Days to <12 Years

• Remdesivir (Veklury)
  • ≥3 to <40 kg: Lyophilized powder only; IV loading dose: 5 mg/kg/dose on Day 1, followed by 2.5 mg/kg/dose once daily on Days 2 and 3
  • ≥40 kg: Injection solution or lyophilized powder; IV loading dose: 200 mg on Day 1, followed by 100 mg once daily on Days 2 and 3

Aged ≥12 Years and ≥40 kg

• Nirmatrelvir 300 mg and ritonavir 100 mg, administered together (Paxlovid), twice daily for 5 days

Hospitalized Children

• Remdesivir (Veklury)
  • ≥3 to <40 kg: Lyophilized powder only; IV loading dose: 5 mg/kg/dose on Day 1, followed by 2.5 mg/kg/dose once daily on Days 2 through
  • ≥40 kg: Injection solution or lyophilized powder; IV loading dose: 200 mg on Day 1, followed by 100 mg once daily on Days 2 through 5
• Dexamethasone 0.15 mg/kg (with a maximum dose of 6 mg), oral or IV, once daily for up to 10 days

Non-hospitalized Children at High Risk of Progression to Severe COVID-‍19

Aged ≥28 Days to <12 Years

• N/A

Aged ≥12 Years

• Remdesivir (Veklury)
  • ≥3 to <40 kg: Lyophilized powder only, IV: loading dose: 5 mg/kg/dose on Day 1, followed by 2.5 mg/kg/dose once daily on Days 2 and 3

Remdesivir is administered intravenously. When given to non-hospitalized patients, duration is for 3 days. When given to hospitalized patients, duration is generally 5 days or until hospital discharge, whichever is first, but may extend to up to 10 days based on clinical response. Remdesivir should be started within 7 days of symptom onset but could be considered if presenting with >7 days of symptoms in children with severe immunosuppression.

Ritonavir-boosted nirmatrelvir is an oral PI that may be administered with other ARVs, including those that contain ritonavir or cobicistat, without any interruption or modification to the usual ART. However, there is potential for significant drug–drug interactions with other medications, requiring dose or frequency adjustment or avoidance. Consult a drug interactions database, such as the University of Liverpool COVID-19 Drug–Drug Interaction website, for further guidance. Ritonavir-boosted nirmatrelvir should be started within 5 days of symptom onset. Renal and hepatic function should be evaluated prior to initiating ritonavir-boosted nirmatrelvir, and doses should be adjusted if needed.

Dexamethasone has potential for drug–drug interactions, including with NNRTIs. Providers should consult a drug interactions resource, such as the University of Liverpool COVID-19 Drug–Drug Interaction website, for further guidance. Alternative corticosteroids, such as hydrocortisone or methylprednisolone, may be considered if dexamethasone is not available or if alternative corticosteroids are being administered for another indication.

CNS Disease
Acute Therapy (Minimum 2-Week Induction Followed by Consolidation Therapy)

• Amphotericin B deoxycholate 1.0 mg/kg body weight (or liposomal amphotericin B 6 mg/kg body weight) IV once daily plus flucytosine 25 mg/kg body weight per dose by mouth given 4 times daily

Consolidation Therapy (Followed by Secondary Prophylaxis)

• Fluconazole 12 mg/kg body weight on day 1, then 10–12 mg/kg body weight (max 800 mg) once daily IV or by mouth for a minimum of 8 weeks

CNS Disease

Acute Therapy (Minimum 2-Week Induction Followed by Consolidation Therapy)

• If Flucytosine Not Tolerated or Unavailable—

   

  • A. Liposomal amphotericin B, 6 mg/kg body weight IV once daily, or Amphotericin B Lipid Complex, 5 mg/kg body weight IV once daily, or Amphotericin B deoxycholate, 1.0–1.5 mg/kg body weight IV once daily alone or B. in combination with high-dose fluconazole (12 mg/kg body weight on day 1 and then 10–‍12 mg/kg body weight [max 800 mg] IV). Note: Data-driven pediatric dosing guidelines are unavailable for fluconazole with use of such combination therapy. 

• If Amphotericin B-Based Therapy Not Tolerated—

   

  • Fluconazole, 12 mg/kg body weight on day 1 and then 10–‍12 mg/kg body weight (maximum 800 mg) IV or by mouth once daily plus flucytosine, 25 mg/kg body weight per dose by mouth given 4 times daily 

     

• Consolidation Therapy (Followed by Secondary Prophylaxis)
  • Itraconazole 5–10 mg/kg body weight by mouth given once daily, or 2.5–‍5 mg/kg body weight given twice daily (maximum 200 mg/dose) for a minimum of 8 weeks. A loading dose (2.5–5 mg/kg body weight per dose 3 times daily) is given for the first 3 days (maximum 200 mg/dose; 600 mg/day). See comment on itraconazole under Other Options/Issues.

Localized Disease, Including Isolated Pulmonary Disease (CNS Not Involved)^a

• Fluconazole 12 mg/kg body weight on day 1 and then 6–12 mg/kg body weight (maximum 600 mg) IV or by mouth once daily

Localized Disease Including Isolated Pulmonary Disease (CNS Not Involved)^a

• Amphotericin B, 0.7–1.0 mg/kg body weight, or
• Amphotericin liposomal 3–5 mg/kg body weight, or
• Amphotericin lipid complex, 5 mg/kg body weight IV once daily

Disseminated Disease (CNS Not Involved) or Severe, Pulmonary Disease^a

• Amphotericin B 0.7–1.0 mg/kg body weight, or 
• Liposomal amphotericin, 3–5 mg/kg body weight, or
• Amphotericin B lipid complex 5 mg/kg body weight IV once daily (± flucytosine)

Disseminated Disease (CNS Not Involved) or Severe, Pulmonary Disease^a

• Fluconazole, 12 mg/kg body weight on day 1 and then 6–12 mg/kg body weight (maximum 600 mg) IV or by mouth once daily

Effective ART

• Immune reconstitution might lead to parasitologic and clinical response

There is no consistently effective therapy for cryptosporidiosis in patients with HIV infection; optimized ART and a trial of nitazoxanide should be considered.

Nitazoxanide

• 1–3 years of age: Nitazoxanide (20 mg/mL oral solution) 100 mg orally twice daily with food
• 4–11 years of age: Nitazoxanide (20 mg/mL oral solution) 200 mg orally twice daily with food
• ≥12 years of age: Nitazoxanide tablet 500 mg orally twice daily with food

Treatment Duration

• 3–14 days

Supportive Care

• Hydration, correct electrolyte abnormalities, nutritional support

Antimotility agents (such as loperamide) should be used with caution in young children.

Symptomatic Congenital Infection with Neurologic Involvement

• Ganciclovir 6 mg/kg body weight per dose IV every 12 hours for 6 weeks, or
• Valganciclovir 16 mg/kg body weight per dose orally twice daily for 6 months

Data on valganciclovir dosing in young children for treatment of retinitis are unavailable, but consideration can be given to transitioning from IV ganciclovir to oral valganciclovir after improvement of retinitis is noted.

Intravitreal injections of ganciclovir, foscarnet, or cidofovir are used in adults for retinitis but are not practical for most children.

Combination ganciclovir and foscarnet is associated with substantial rates of adverse effects, and optimal treatment for neurologic disease in children is unknown, particularly if receiving optimized ART.

Chronic suppressive therapy (secondary prophylaxis) is recommended in adults and children following initial therapy of disseminated disease, retinitis, neurologic disease, or GI disease with relapse. 

Disseminated Disease and Retinitis

Induction Therapy

• Ganciclovir 5 mg/kg body weight per dose IV every 12 hours for 14–21 days (may be increased to 7.5 mg/kg body weight per dose IV twice daily)

Chronic Maintenance Therapy

• Ganciclovir 5 mg/kg body weight once daily for 5–7 days

Disseminated Disease and Retinitis

Induction Therapy

• Foscarnet, 60 mg/kg body weight per dose IV every 8 hours or 90 mg/kg body weight per dose IV every 12 hours x 14–21 days,

Chronic Maintenance Therapy

• Foscarnet 90–120 mg/kg body weight IV once daily

Alternative Therapy for Retinitis (Followed by Chronic Maintenance Therapy; See Cytomegalovirus row in Secondary Prophylaxis Table)

• Valganciclovir tablets 900 mg per dose orally twice daily for 14–21 days, followed by chronic suppressive therapy (see above). Note: This is an option in older children who can receive the adult dose (based on their BSA) and in patients with mild disease. 
• IV ganciclovir plus IV foscarnet (at above induction doses) may be considered as initial induction therapy in children with sight-threatening disease or for treatment following failure/relapse on monotherapy.
• Cidofovir is also used to treat CMV retinitis in adults intolerant to other therapies. Induction dosing in adults is 5 mg/kg body weight IV once weekly for 2 weeks, followed by chronic suppressive therapy (see Cytomegalovirus row in Secondary Prophylaxis Table); however, data on dosing in children are unavailable. Must be given with probenecid and IV hydration

Central Nervous System Disease

Induction Therapy

• Ganciclovir 5 mg/kg body weight per dose IV every 12 hours plus foscarnet 60 mg/kg body weight per dose IV every 8 hours (or 90 mg/kg body weight per dose IV every 12 hours) continued until symptomatic improvement

Chronic Maintenance Therapy

• See Cytomegalovirus row in Secondary Prophylaxis table.

• Tinidazole, 50 mg/kg by mouth, administered as 1 dose given with food (maximum 2 g).

Note: Based on data from children who are HIV-negative

• Nitazoxanide
  • 1–3 years: 100 mg by mouth every 12 hours with food for 3 days
  • 4–11 years: 200 mg by mouth every 12 hours with food for 3 days
  • ≥12 years: 500 mg by mouth every 12 hours with food for 3 days

Note: Based on data from children who are HIV-negative

Tinidazole is FDA-approved in the United States for children aged ≥3 years. It is available in tablets that can be crushed.

Metronidazole has a high frequency of gastrointestinal side effects. A pediatric suspension of metronidazole is not commercially available but can be compounded from tablets. Metronidazole is not FDA-approved for the treatment of giardiasis.

Supportive Care

• Hydration
• Correction of electrolyte abnormalities
• Nutritional support

Antimotility agents (e.g., loperamide) should be used with caution in young children.

Treatment of Only HBV Required (Child Does Not Require cART)

• IFN-α 3 million units/m² body surface area SQ 3 times a week for 1 week, followed by dose escalation to 6 million units/m² body surface area (max 10 million units/dose), to complete a 24-week course, or
• For children aged ≥12 years, adefovir 10 mg by mouth once daily for a minimum of 12 months (uncertain if risk of HIV resistance)

Treatment of Both HIV and HBV Required (Child Not Already Receiving 3TC or FTC)

• 3TC 4 mg/kg body weight (maximum 150 mg) per dose by mouth twice daily as part of a fully suppressive cART regimen
• For children aged ≥2 years, include TDF as part of cART regimen with 3TC or FTC. For children aged ≥12, TDF dose is 300 mg once daily. For children aged <12 year, and 8 mg/kg body weight per dose once daily (maximum dose 300 mg) 

Treatment of Both HIV and HBV Required (Child Already Receiving cART Containing 3TC or FTC, Suggesting 3TC/FTC Resistance)

• For children aged ≥2 years, include TDF as part of cART regimen with 3TC or FTC. For children aged ≥12 years, TDF dose is 300 mg once daily. For children aged <12 years, 8 mg/kg body weight per dose once daily (maximum dose 300 mg) 
• For children aged ≥12 years, add adefovir 10 mg by mouth once daily or entecavir 0.5 mg by mouth once daily in addition to cART regimen.
• For children aged <12 years, give 6-month course of IFN-α as above in addition to cART regimen.

• IFN-α 10 million units/m² body surface area SQ 3 times a week for 6 months (sometimes used for retreatment of failed lower-dose interferon therapy)
• Alternative for 3TC: FTC 6 mg/kg body weight (maximum 200 mg) once daily

Indications for Treatment Include

• Detectable serum HBV DNA, irrespective of HBeAg status, for >6 months; and
• Persistent (>6 months) elevation of serum transaminases (≥ twice the upper limit of normal); or
• Evidence of chronic hepatitis on liver biopsy

IFN-α is contraindicated in children with decompensated liver disease; significant cytopenias, severe renal, neuropsychiatric, or cardiac disorders; and autoimmune disease. 

Choice of HBV treatment options for HIV/HBV-co-infected children depends upon whether concurrent HIV treatment is warranted.

3TC and FTC have similar activity (and have cross-resistance) and should not be given together. FTC is not FDA-approved for treatment of HBV.

TDF is approved for use in treatment of HIV infection in children aged ≥2 years but it is not approved for treatment of HBV infection in children aged <12 years. It should only be used for HBV in HIV/HBV-infected children as part of a cART regimen.

Adefovir is approved for use in children aged ≥12 years. 

ETV is not approved for use in children younger than age 16 years, but is under study in HIV-uninfected children for treatment of chronic hepatitis B. Can be considered for older HIV-infected children who can receive adult dosage. It should only be used for HBV in HIV/HBV-infected children who also receive an HIV-suppressive cART regimen.

IRIS may be manifested by dramatic increase in transaminases as CD4 cell counts rise within the first 6 to 12 weeks of cART. It may be difficult to distinguish between drug-induced hepatotoxicity and other causes of hepatitis and IRIS.

In children receiving TDF and 3TC or FTC, clinical and laboratory exacerbations of hepatitis (flare) may occur if the drug is discontinued; thus, once anti-HIV/HBV therapy has begun, it should be continued unless contraindicated or until the child has been treated for >6 months after HBeAg seroconversion and can be closely monitored on discontinuation. 

If anti-HBV therapy is discontinued and a flare occurs, reinstitution of therapy is recommended because a flare can be life threatening.

Telbivudine has been approved for use in people aged ≥16 years with HBV; there are no data on safety or efficacy in children aged <16 years; a pharmacokinetic study is under way in HIV-uninfected children.

IFN-α Plus Ribavirin Combination Therapy 

• Pegylated IFN-α: Peg-IFN 2a 180 µg/1.73 m² body surface area subcutaneously once per week (maximum dose 180 µg) OR  Peg-IFN 2b 60 µg/m² body surface area once per week 

PLUS

• Ribavirin (oral) 7.5 mg/kg body weight twice daily (fixed dose by weight recommended):
  • 25–36 kg: 200 mg a.m. and p.m.
  • >36 to 49 kg: 200 mg a.m. and 400 mg p.m.
  • >49 to 61 kg: 400 mg a.m. and p.m.
  • >61 to 75 kg: 400 mg a.m. and 600 mg p.m. 
  • >75 kg: 600 mg a.m. and p.m.

Treatment Duration

• 48 weeks, regardless of HCV genotype 

Neonatal CNS or Disseminated Disease 

• Acyclovir 20 mg/kg body weight IV/dose every 8 hours for ≥21 days 

Neonatal Skin, Eye, or Mouth Disease 

• Acyclovir 20 mg/kg body weight IV/dose every 8 hours for 14 days

CNS or Disseminated Disease in Children Outside the Neonatal Period

• Acyclovir 10 mg/kg body weight (up to 15 mg/kg body weight/dose in children <12 years) IV every 8 hours for 21 days

For Neonatal CNS Disease—

• Repeat CSF HSV DNA PCR should be performed on days 19 to 21 of therapy. If the repeat CSF HSV DNA PCR is positive, continue IV acyclovir for an additional week, repeating the CSF HSV DNA PCR again near the end of extended treatment. Acyclovir should not be stopped until a repeat CSF HSV DNA PCR is negative. 

Moderate to Severe Symptomatic Gingivostomatitis

• Acyclovir 5–10 mg/kg body weight/dose IV every 8 hours. Patients can be switched to oral therapy after lesions have begun to regress and therapy continued until lesions have completely healed. 

Mild Symptomatic Gingivostomatitis

• Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth QID for 7–10 days

Recurrent Herpes Labialis

• Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth QID for 5 days

For First-Episode Genital Herpes (Adults and Adolescents)—

• Acyclovir 20 mg/kg body weight (maximim 400 mg/dose) dose by mouth TID for 7–10 days

• Valacyclovir is approved for immunocompetent adults and adolescents with first-episode mucocutaneous HSV at a dose of 1 g/dose by mouth BID for 7–10 days; also approved for recurrent herpes labialis in children ≥12 years using two, 2 g doses by mouth separated by 12 hours as single-day therapy.
• Recurrent genital HSV can be treated with valacyclovir 500 mg BID for 3 days or 1 g by mouth daily for 5 days. 
• Immunocompetent adults with recurrent herpes labialis can be treated with famciclovir, 1 g/dose by mouth BID for 1 day.
• Famciclovir is approved to treat primary genital HSV in immunocompetent adults at a dose of 250 mg/dose by mouth TID for 7–10 days.
• Recurrent genital HSV is treated with famciclovir 1 g/dose by mouth BID at a 12-hour interval for 2 doses.
• Famciclovir is approved for use in HIV-infected adults and adolescents with recurrent mucocutaneous HSV infection at a dose of 500 mg/dose by mouth BID for 7 days. 

• There is no pediatric preparation of valacyclovir (although crushed capsules can be used to make a suspension according to specific instructions provided in the U.S. FDA package insert) and data on dosing in children are limited. Valacyclovir can be used by adolescents able to receive adult dosing.
• Famciclovir is available in a sprinkle formulation with weight-adjusted dosing. Famciclovir can be used by adolescents able to receive adult dosing.

Recurrent Genital Herpes (Adults and Adolescents)

• Acyclovir 20 mg/kg body weight (maximum 400 mg/dose) dose by mouth TID for 5 days

Children with HSV Keratoconjunctivitis

• Often treated with topical trifluridine (1%) or granciclovir (0.15%) applied as 1–2 drops 5 times daily. Many experts add oral acyclovir to the topical therapy.

Children with ARN

• For children old enough to receive adult dose, acyclovir 10–15 mg/kg body weight/dose IV every 8 hours for 10–14 days, followed by oral valacyclovir 1 g/dose TID for 4–6 weeks
• As an alternative, oral acyclovir 20 mg/kg body weight/dose QID for 4–6 weeks after IV acyclovir for 10–14 days 

Alternative and Short-Course Therapy in Immunocompromised Adults with Recurrent Genital Herpes

• Acyclovir 800 mg per dose by mouth BID for 5 days
• Acyclovir 800 mg per dose by mouth TID for 2 days

Note: Consultation with an ophthalmologist experienced in managing herpes simplex infection involving the eye and its complications in children is strongly recommended when ocular disease is present. 

Acyclovir-Resistant HSV Infection

• Foscarnet 40 mg/kg body weight/dose given IV every 8 hours or 60 mg/kg body weight/dose IV every 12 hours should be administered slowly over the course of 2 hours (i.e., no faster than 1 mg/kg/minute). 

Acute Primary Pulmonary Histoplasmosis

• Itraconazole oral solution loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth twice daily for 12 months. Duration of 12 weeks is sufficient for HIV-infected children, with functional cellular immunity (CD4 percentage >20% or if aged ≥6, CD4 cell count >300 cells/mm³, provided monitoring confirms clinical improvement and decreased urine antigen concentrations. 

Acute Primary Pulmonary Histoplasmosis

• Fluconazole 3–6 mg/kg body weight (maximum 200 mg) by mouth once daily

Mild Disseminated Disease

• Itraconazole oral solution loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth twice daily for 12 months 

Mild Disseminated Disease

• Fluconazole 5–6 mg/kg body weight IV or by mouth (maximum 300 mg) per dose, twice daily (maximum 600 mg/day) for 12 months 

Moderately Severe to Severe Disseminated Disease

Acute Therapy (Minimum 2-Week Induction, Longer if Clinical Improvement is Delayed, Followed by Consolidation Therapy):

• Liposomal amphotericin B 3–5 mg/kg body weight, IV once daily (preferred)
• Amphotericin B deoxycholate 0.7–1 mg/kg body weight IV once daily (alternative)

Consolidation Therapy (Followed by Chronic Suppressive Therapy):

• Itraconazole oral solution initial loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth given twice daily for 12 months 

Moderately Severe to Severe Disseminated Disease

• If itraconazole not tolerated, amphotericin alone for 4–6 weeks can be used with monitoring that confirms decline in histoplasma urine and serum antigen levels.
• Liposomal amphotericin B 3–5 mg/kg body weight IV once daily (preferred) for 4–6 weeks
• Amphotericin B deoxycholate 0.7–1 mg/kg body weight IV once daily (alternative) for 4–6 weeks

Central Nervous System Infection

Acute Therapy (4–6 Weeks, Followed by Consolidation Therapy)

• Liposomal amphotericin B,5 mg/kg body weight IV once daily (AII)

Consolidation Therapy (Followed by Chronic Suppressive Therapy)

• Itraconazole oral solution initial loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth given twice daily for ≥12 months and until histoplasma antigen is no longer detected in cerebrospinal fluid

• Podofilox solution/gel (0.5%) applied topically BID for 3 consecutive days a week up to 4 weeks (patient applied). Withhold treatment for 4 days and repeat the cycle weekly up to 4 times (BIII) 
• Imiquimod cream (5%) applied topically at night and washed off in the morning for 3 non-consecutive nights a week for up to 16 weeks (patient applied) (BII)
• TCA or BCA (80%–90%) applied topically weekly for up to 3 to 6 weeks (provider applied) (BIII)
• Podophyllin resin (10%–25% suspension in tincture of benzoin) applied topically and washed off several hours later, repeated weekly for 3 to 6 weeks (provider applied) (CIII)
• Cryotherapy with liquid nitrogen or cryoprobe applied every 1–2 weeks (BIII)
• Surgical removal either by tangential excision, tangential shave excision, curettage, or electrosurgery

• Intralesional IFN-α is generally not recommended because of high cost, difficult administration, and potential for systemic side effects (CIII)
• Cidofovir topical gel (1%) is an experimental therapy studied in HIV-infected adults that is commercially available through compounding pharmacies and has very limited use in children; systemic absorption can occur (CIII).
• 5-FU/epinephrine gel implant should be offered in only severe recalcitrant cases because of inconvenient routes of administration, frequent office visits, and a high frequency of systemic adverse effects.

Pyrimethamine 1 mg/kg body weight (maximum 25 mg) plus folinic acid 5–15 mg by mouth once daily for 14 days

Second-Line Alternatives

• Ciprofloxacin 10–20 mg/kg body weight (maximum 500 mg) by mouth twice daily for 7 days
• Nitazoxanide (see doses below) for 3 consecutive days

Children Aged 1 Year–3 Years

• Nitazoxanide 100 mg by mouth every 12 hours

Children Aged 4 Years–11 years

• Nitazoxanide 200 mg by mouth every 12 hours

Adolescents Aged ≥12 Years and Adults

• Nitazoxanide 500 mg by mouth every 12 hours

Uncomplicated P. Falciparum or Unknown Malaria Species, from Chloroquine-Resistant Areas (All Malaria Areas Except Those Listed as Chloroquine Sensitive) or Unknown Region:

• Atovaquone-proguanil (pediatric tablets 62.5 mg/25 mg; adult tablets 250 mg/100 mg), dosed once daily: 
  • 5–8 kg; 2 pediatric tablets for 3 days; 
  • 9–10 kg; 3 pediatric tablets for 3 days; 
  • 11–20 kg; 4 pediatric tablets or 1 adult tablet for 3 days; 
  • 21–30 kg; 2 adult tablets for 3 days; 
  • 31–40 kg; 3 adult tablets for 3 days; 
  • >40 kg; 4 adult tablets for 3 days 

Uncomplicated P. Falciparum OR Unknown Malaria Species from Chloroquine-Sensitive Region (See Comments for Link to Resistance Map): 

• Chloroquine phosphate: 16.6 mg/kg body weight (10 mg/kg body weight chloroquine base) (maximum 1,000 mg) by mouth once, then 8.3 mg/kg body weight (maximum 500 mg) by mouth at 6, 24, and 48 hours (total dose = 41.6 mg/kg body weight chloroquine phosphate [maximum 2,500 mg] = 25 mg/kg body weight chloroquine base)

P. vivax, P. ovale, P. malariae, P. knowlesi (All Areas Except Papua New Guinea, Indonesia; See Comments)
Initial Therapy (Followed by Anti-Relapse Therapy for P. ovale and P. vivax):

• Chloroquine phosphate 16.6 mg/kg body weight (10 mg/kg body weight chloroquine base) (maximum 1,000 mg) by mouth once, then 8.3 mg/kg body weight (maximum 500 mg) by mouth at 6, 24, and 48 hours (total dose = 41.6 mg/kg body weight chloroquine phosphate [maximum 2,500 mg] = 25 mg/kg body weight chloroquine base) 

Anti-Relapse Therapy for P. ovale, P. vivax:

• Primaquine 0.5 mg base/kg body weight (max 30 mg base) by mouth once daily for 14 days

Uncomplicated P. falciparum or Unknown Malaria Species from Chloroquine-Resistant Areas (All Malaria Areas Except Those Listed as Chloroquine Sensitive) or Unknown Region:

• Mefloquine (250-mg tablets only): 15 mg/kg body weight (maximum 750 mg) by mouth once, then 10 mg/kg body weight (maximum 500 mg) by mouth given 12 hours later 
• Quinine sulfate 10 mg/kg body weight (maximum 650 mg) per dose by mouth every 8 hours for 3 to 7 days, plus Clindamycin 7 mg/kg body weight per dose by mouth every 8 hours for 7 days, or doxycycline: 2.2 mg/kg body weight per dose (maximum 100 mg) given by mouth every 12 hours, or tetracycline 6–12.5 mg/kg body weight per dose by mouth given every 6 hours (maximum dose: 500 mg per dose given 4 times daily) for 7 days.
• Artemether-lumefantrine: 1 tablet=20 mg Artemether and 120 mg lumefantrine, a 3-day treatment schedule for a total of 6 doses. The second dose follows the initial dose 8 hours later, then 1 dose twice daily for the next 2 days. 
  • 5 to <15 kg; 1 tablet per dose
  • 15 to <25 kg; 2 tablets per dose
  • 25 to <35 kg; 3 tablets per dose
  • >35 kg; 4 tablets per dose

For quinine-based regimens, doxycycline or tetracycline should be used only in children aged ≥8 years. An alternative for children aged ≥8 years is clindamycin 7 mg/kg body weight per dose by mouth given every 8 hours. Clindamycin should be used for children aged <8 years.

Before primaquine is given, G6PD status must be verified. Primaquine may be given in combination with chloroquine if the G6PD status is known and negative, otherwise give after chloroquine (when G6PD status is available)

For most updated prevention and treatment recommendations for specific region, refer to updated CDC treatment table available at http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf  

For sensitive and resistant malaria map: https://www.cdc.gov/malaria/travelers/country_table/a.html

High treatment failure rates due to chloroquine-resistant P. vivax have been documented in Papua New Guinea and Indonesia. Treatment should be selected from one of the three following options:

• Atovaquone-proguanil plus primaquine phosphate
• Quinine sulfate plus either doxycycline or tetracycline plus primaquine phosphate. This regimen cannot be used in children aged <8 years.
• Mefloquine plus primaquine phosphate

• Quinidine gluconate 10 mg/kg body weight IV loading dose over 1–2 hours, then 0.02 mg/kg body weight/minute infusion for ≥24 hours (Treatment duration: 7 days in Southeast Asia, Oceania, otherwise 3 days)
  
  PLUS One of the Following:
• Doxycycline 100 mg per dose by mouth every 12 hours for 7 days; for children <45 kg, use 2.2 mg/kg body weight per dose
  OR
• Clindamycin 7 mg/kg body weight per dose by mouth given every 8 hours for 7 days.
  OR
• Tetracycline 6–12.5 mg/kg body weight per dose every 6 hours (maximum dose 500 mg per dose given 4 times daily) for 7 days
• Artesunate 2.4 mg/kg body weight IV bolus at 0, 12, 24, and 48 hours
  
  PLUS One of the Following:
• Doxycycline (treatment dosing as above), or Atovaquone-proguanil (treatment dosing as above), or
• Mefloquine 15 mg/kg body weight (maximum 750 mg) by mouth once, then 10 mg/kg body weight (maximum 500 mg) by mouth once given 12 hours later, or
• Clindamycin (dosing as above)

Quinidine gluconate is a class 1a anti-arrhythmic agent not typically stocked in pediatric hospitals. When regional supplies are unavailable, the CDC Malaria hotline may be of assistance (see below). Do not give quinidine gluconate as an IV bolus. Quinidine gluconate IV should be administered in a monitored setting. Cardiac monitoring required. Adverse events including severe hypoglycemia, prolongation of the QT interval, ventricular arrhythmia, and hypotension can result from the use of this drug at treatment doses.

IND: IV artesunate is available from CDC. Contact the CDC Malaria Hotline at (770) 488-7788 from 8 a.m.–4:30 p.m. EST or (770) 488-7100 after hours, weekends, and holidays. Artesunate followed by one of the following: Atovaquone-proguanil (Malarone™), clindamycin, mefloquine, or (for children aged >8 years) doxycycline.

Quinidine gluconate: 10 mg = 6.25 mg quinidine base.

Doxycycline (or tetracycline) should be used in children aged ≥8 years. For patients unable to take oral medication, may give IV. For children <45 kg, give 2.2 mg/kg IV every 12 hours and then switch to oral doxycycline. For children >45 kg, use the same dosing as per adults. For IV use, avoid rapid administration.

For patients unable to take oral clindamycin, give 10 mg base/kg loading dose IV, followed by 5 mg base/kg IV every 8 hours. Switch to oral clindamycin (oral dose as above) as soon as a patient can take oral medication. For IV use, avoid rapid administration.

Drug Interactions:

• Avoid co-administration of quinidine with ritonavir.
• Use quinidine with caution with other protease inhibitors.

Effective ART Therapy

• Immune reconstitution may lead to microbiologic and clinical response. 

For Disseminated (Not Ocular) and Intestinal Infection Attributed to Microsporidia Other Than E. bieneusi or V. corneae—

• Albendazole 7.5 mg/kg body weight (maximum 400 mg/dose) by mouth twice daily (in addition to ART)

Treatment Duration

• Continue until sustained immune reconstitution (longer than 6 months at CDC immunologic category 1 or 2) after initiation of ART and resolution of signs and symptoms 

For E. bieneusi or V. corneae Infections—

• Fumagillin (where available) adult dose 20 mg by mouth 3 times daily, or
• TNP-470 (a synthetic analogue of fumagillin; where available) recommended for treatment of infections caused by E. bieneusi in HIV-infected adults (in addition to ART)

For Ocular Infection—

• Topical fumagillin bicyclohexylammonium (Fumidil B) 3 mg/mL in saline (fumagillin 70 µg/mL) eye drops: 2 drops every 2 hours for 4 days, then 2 drops QID (investigational use only in United States) plus, for microsporidial infection other than E. bieneusi and V. corneae, albendazole 7.5 mg/kg body weight (maximum 400 mg/dose) by mouth twice daily for management of systemic infection in systemic infection (in addition to ART) 

Treatment Duration

• Continue until sustained immune reconstitution (longer than 6 months at CDC immunologic category 1 or 2) after initiation of ART and resolution of signs and symptoms. 

• Supportive care (e.g., hydration, correction of electrolyte abnormalities, nutritional support)
• Fumagillin for systemic use is unavailable in the United States and data on dosing in children are unavailable. Consultation with an expert is recommended. 

Initial Treatment (≥2 Drugs)

• Clarithromycin 7.5–15 mg/kg body weight (maximum 500 mg/dose) orally twice daily plus ethambutol 15–25 mg/kg body weight (maximum 2.5 g/day) orally once daily followed by chronic suppressive therapy

For Severe Disease, Add—

• Rifabutin 10–20 mg/kg body weight (maximum 300 mg/day) orally once daily

If Intolerant to Clarithromycin—

• Azithromycin 10–12 mg/kg body weight (maximum 500 mg/day) orally once daily

If Rifabutin Cannot Be Administered and a Third Drug is Needed in Addition to a Macrolide and Ethambutol, or if a Fourth Drug is Needed in Addition to Rifabutin for Patients with More Severe Symptoms or Disseminated Disease—

• Ciprofloxacin 10–15 mg/kg orally twice daily (maximum 1.5 g/day), or
• Levofloxacin 500 mg orally once daily, or
• Amikacin 15–30 mg/kg body weight IV in 1 or 2 divided doses (maximum 1.5 g/day)

Intrathoracic Disease
Drug-Susceptible TB

• Intensive Phase (2 months)
  • Isoniazid, 10–15 mg/kg body weight (maximum 300 mg/day) by mouth once daily, plus
  • Rifampin 15–20 mg/kg body weight^a (maximum 600 mg/day) by mouth once daily, plus
  • Pyrazinamide 30–40 mg/kg body weight (maximum 2 g/day) by mouth once daily, plus
  • Ethambutol 15–25 mg/kg body weight (maximum 1 g/day) by mouth once daily
  • In children with minimal disease with fully drug-susceptible TB, some experts recommend a three-‍drug intensive phase regimen excluding ethambutol.
• Continuation Phase (4 Months) 
  • Isoniazid 10–15 mg/kg body weight (maximum 300 mg/day) by mouth once daily, plus 
  • Rifampin 15–20 mg/kg body weight^a (maximum 600 mg/day) by mouth once daily 

Extrathoracic Disease
Note: Depends on disease entity

• Lymph node TB—treat as minimal intrathoracic disease
• Bone or joint disease–consider extending continuation phase to 10 months (for total duration of therapy of 12 months).

TB Meningitis

• As an alternative to ethambutol, streptomycin 20–40 mg/kg body weight (maximum 1 g/day) IM once daily. During intensive phase, consider ethionamide, 15–20 mg/kg body weight by mouth (maximum 1 g/day), initially divided into two doses until well tolerated.
• Many experts recommend rifampin doses of 20–30 mg/kg daily for treatment of TB meningitis. See the AAP Red Book and WHO Operational Handbook on Tuberculosis for more information.
• Consider extending continuation phase to 10 months (for total duration of therapy of 12 months). 
• Discuss with an expert.

Drug-Resistant TB

• Therapy should be based on resistance pattern of child (or of source case where child’s isolate is not available); consult an expert. 

Alternative for Rifampin 

• Rifabutin 10–20 mg/kg body weight (maximum 300 mg/day) by mouth once daily (same dose if three times a week) 
• Discuss with an expert.

Alternative Continuation Phase with Three Times Weekly Dosing (4 Months)
If Good Adherence and Treatment Response

• Isoniazid 20–30 mg/kg body weight (maximum 900 mg/day) by mouth three times per week, plus
• Rifampin 15–20 mg/kg body weight (maximum 600 mg/day) three times per week
• In children with minimal disease with fully drug-susceptible TB, some experts recommend a continuation phase of 4 months (total duration of therapy of 6 months)

Treatment for TB disease should always be provided by DOT.

If ART-naive, start TB therapy immediately and initiate ART within 2–‍8 weeks. 

If already on ART, review regimen to minimize potential toxicities and drug interactions; start TB treatment immediately.

Potential drug toxicity and interactions should be reviewed at every visit. Drug interactions with ART should be considered for all rifamycin-containing alternatives.

Adjunctive Treatment

• Co-trimoxazole prophylaxis 
• Pyridoxine 1–2 mg/kg/ body weight/day (maximum 25–50 mg/day) with isoniazid or cycloserine/terizidone or, if malnourished. Pyridoxine supplementation is recommended for exclusively breastfed infants and for children and adolescents on meat- and milk-deficient diets; children with nutritional deficiencies, including all children with HIV; and pregnant adolescents and people.
• Corticosteroids (2 mg/kg body weight per day of prednisone [maximum, 60 mg/day] or its equivalent for 4–6 weeks followed by tapering) with TB meningitis; may be considered with pleural effusions, severe airway compression, or severe IRIS.

Second-Line Drug Doses

• Consult with an expert as dosing guidelines continue to evolve with emerging data.

^a Some experts recommend using a daily rifampin dose of 20–‍30 mg/kg/day for infants and toddlers.

If TMP-SMX-Intolerant or Clinical Treatment Failure After 5–7 Days of TMP-SMX Therapy
Pentamidine:

• 4 mg/kg body weight/dose IV/IM once daily is the first choice alternative regimen. Note: Pentamidine can be changed to atovaquone after 7–10 days IV therapy.

Atovaquone 
Daily Dosing: 

• Children aged 1–3 months and >24 months–12 years: 30-40 mg/kg body weight/dose by mouth once daily with food 
• Children aged 4–24 months: 45 mg/kg body weight/dose by mouth once daily with food
  Twice-Daily Dosing*:
• Children aged ≥13 years: 750 mg/dose by mouth twice daily

* Some experts use twice-daily dosing of atovaquone as alternative treatment for PCP in children aged <12 years:

• Children aged 1–3 months and >24 months to 12 years: 15–20 mg/kg body weight /dose by mouth twice daily with food 
• Children aged 4–24 months: 22.5 mg/kg body weight/dose by mouth twice daily with food.

After acute pneumonitis resolved in mild-moderate disease, IV TMP-SMX can be changed to oral. For oral administration, total daily dose of TMP-SMX can also be administered in 3 divided doses (every 8 hours).

Dapsone 2 mg/kg body weight by mouth once daily (maximum 100 mg/day) plus trimethoprim 5 mg/kg body weight by mouth every 8 hours has been used in adults but data in children are limited. 

Primaquine base 0.3 mg/kg body weight by mouth once daily (maximum 30 mg/day) plus clindamycin 10mg/kg body weight/dose IV or by mouth (maximum 600 mg given IV and 300–450 mg given orally) every 6 hours has been used in adults, but data in children are not available. 

Indications for Corticosteroids:

• PaO₂ <70 mm Hg at room air or alveolar-arterial oxygen gradient >35 mm Hg 

Prednisone Dose

• 1 mg/kg body weight/dose by mouth twice daily for 5 days, then 
• 0.5–1 mg/kg body weight/dose by mouth twice daily for 5 days, then 
• 0.5 mg/kg body weight by mouth once daily for days 11 to 21. 

Alternative Corticosteroid Regimens Include- 

• Adult dosage of prednisone: 40 mg/dose twice daily on days 1–5, 40 mg/dose once daily on days 6–10, 20 mg/dose once daily on days 11–21, and 
• Methylprednisolone IV 1 mg/kg/dose every 6 hours on days 1–7, 1 mg/kg/dose twice daily on days 8–9, 0.5 mg/kg/dose twice daily on days 10 and 11, and 1 mg/kg/dose once daily on days 12–16.

Chronic suppressive therapy (secondary prophylaxis) with TMP/SMX is recommended in children and adults following initial therapy (see Secondary Prophylaxis).

Congenital
Proven or Highly Probable Disease:

• Aqueous crystalline penicillin G 100,000–150,000 units/kg body weight per day, administered as 50,000 units/kg body weight per dose IV every 12 hours for the first 7 days of life, and then every 8 hours for 10 days 
• If diagnosed after 1 month of age, aqueous penicillin G 200,000–300,000 unit/kg body weight per day, administered as 50,000 units/kg body weight per dose IV every 4–6 hours (maximum 18–24 million units per day) for 10 days 

Possible Disease:

• Treatment options are influenced by several factors, including maternal treatment, titer, and response to therapy; and infant physical exam, titer, and test results. Scenarios that include variations of these factors are described and treatment recommendations are provided in detail on pages 36–37 of the Centers for Disease Control STD Treatment Guidelines, 2010. 

Acquired:
Early Stage (Primary, Secondary, Early Latent):

• Benzathine penicillin 50,000 units/kg body weight (maximum 2.4 million units) IM for 1 dose 

Late Latent:

• Benzathine penicillin 50,000 units/kg body weight (maximum 2.4 million units) IM once weekly for 3 doses 

Neurosyphilis (Including Ocular):

• Aqueous penicillin G 200,000–300,000 units/kg body weight per day administered as 50,000 units/kg body weight per dose IV every 4–6 hours (maximum 18–24 million units per day) for 10–14 days 

Congenital
Proven or Highly Probable Disease (Less Desirable if CNS Involvement):

• Procaine penicillin G 50,000 units/kg body weight IM once daily for 10 days 

Possible Disease:

• Treatment options are influenced by several factors, including maternal treatment, titer, and response to therapy; and infant physical exam, titer, and test results. Scenarios that include variations of these factors are described and treatment recommendations are provided in detail on pages 36–37 of the Centers for Disease Control STD Treatment Guidelines, 2010. 

Congenital Toxoplasmosis: 

• Pyrimethamine loading dose–2 mg/kg body weight by mouth once daily for 2 days, then 1 mg/kg body weight by mouth once daily for 2–6 months, then 1 mg/kg body weight by mouth 3 times weekly, plus 
• Leucovorin (folinic acid) 10 mg by mouth or IM with each dose of pyrimethamine, plus
• Sulfadiazine 50 mg/kg body weight by mouth twice daily

Treatment Duration:

• 12 months 

Acquired Toxoplasmosis
Acute Induction Therapy (Followed by Chronic Suppressive Therapy):

• Pyrimethamine: loading dose—2 mg/kg body weight (maximum 50 mg) by mouth once daily for 3 days, then 1 mg/kg body weight (maximum 25 mg) by mouth once daily, plus 
• Sulfadiazine 25–50 mg/kg body weight (maximum 1–1.5 g/dose) by mouth per dose 4 times daily, plus
• Leucovorin 10–25 mg by mouth once daily, followed by chronic suppressive therapy

Treatment Duration (Followed by Chronic Suppressive Therapy): 

• ≥6 weeks (longer duration if clinical or radiologic disease is extensive or response in incomplete at 6 weeks) 

For Sulfonamide-Intolerant Patients:

• Clindamycin 5–7.5 mg/kg body weight (maximum 600 mg/dose) by mouth or IV per dose given 4 times a day can be substituted for sulfadiazine combined with pyrimethamine and leucovorin 

Congenital Toxoplasmosis:

• For infants born to mothers with symptomatic Toxoplasma infection during pregnancy, empiric therapy of the newborn should be strongly considered irrespective of the mother’s treatment during pregnancy. 

Acquired Toxoplasmosis:

• Pyrimethamine use requires CBC monitoring at least weekly while on daily dosing and at least monthly while on less than daily dosing. 
• TMP-SMX—TMP 5 mg/kg body weight plus SMX 25 mg/kg body weight per dose IV or by mouth given twice daily has been used as an alternative to pyrimethamine-sulfadiazine in adults, but has not been studied in children. 
• Atovaquone (for adults, 1.5 g by mouth twice daily—double the prophylaxis dose) in regimens combined with pyrimethamine/leucovorin, with sulfadiazine alone, or as a single agent in patients intolerant to both pyrimethamine and sulfadiazine, has been used in adults, but these regimens have not been studied in children. 
• Azithromycin (for adults, 900–1,200 mg/day, corresponding to 20 mg/kg/day in children) has also been used in adults combined with pyrimethamine-sulfadiazine, but has not been studied in children.
• Corticosteroids (e.g., prednisone, dexamethasone) have been used in children with CNS disease when CSF protein is very elevated (>1,000 mg/dL) or there are focal lesions with significant mass effects, with discontinuation as soon as clinically feasible. 
• Anticonvulsants should be administered to patients with a history of seizures and continued through the acute treatment; but should not be used prophylactically. 

Varicella
Children with No or Moderate Immune Suppression (CDC Immunologic Categories 1 and 2) and Mild Varicella Disease:

• Acyclovir 20 mg/kg body weight/dose by mouth (maximum 800 mg/dose) four times a day for 7–10 days and until no new lesions for 48 hours

Children with Severe Immune Suppression or Severe Varicella Disease (see text):

• Acyclovir 10 mg/kg body weight or 500 mg/m²/dose IV every 8 hours for 7–10 days and until no new lesions for 48 hours

Zoster 
Children with Uncomplicated Zoster and No or Moderate Immune Suppression:

• Acyclovir 20 mg/kg body weight/dose (maximum 800 mg/dose) by mouth four times a day for 7–10 days.

Children with Severe Immunosuppression (CDC Immunologic Category 3), Trigeminal or Sacral Nerve Involvement, Extensive Multidermatomal, or Disseminated Zoster:

• Acyclovir 10 mg/kg body weight/dose or 500 mg/m² IV every 8 hours until cutaneous lesions and visceral disease are clearly resolving, then can switch to oral acyclovir to complete a 10–14-day course

Children with Progressive Outer Retinal Necrosis:

• Acyclovir (10 mg/kg or 500 mg/m² every 8 hours) or ganciclovir 5 mg/kg body weight/dose IV every 12 hours, plus
• Foscarnet 90 mg/kg body weight/dose IV every 12 hours, plus
• Ganciclovir 2 mg/0.05 mL intravitreal injection twice weekly and/or foscarnet 1.2 mg/0.05 mL intravitreal injection twice weekly

Children with Acute Retinal Necrosis:

• Acyclovir 10–15 mg/kg body weight/dose IV every 8 hours daily for 10–14 days, followed by oral valacyclovir 1 g/dose three times a day for 4–6 weeks (for children old enough to receive adult dose).
• Alternative to oral valacyclovir is oral acyclovir 20 mg/kg body weight/dose four times a day for 4–6 weeks

Patients Unresponsive to Acyclovir:

• Foscarnet (40–60 mg/kg body weight/dose IV every 8 hours) for 7-10 days or until no new lesions have appeared for 48 hours

Key: AAP = American Academy of Pediatrics; ART = antiretroviral therapy; BCA = bicholoracetic acid; BID = twice daily; BSA = body surface area; cART = combination antiretroviral therapy; CNS = central nervous system; CrCl = (estimated) creatinine clearance; CSF = cerebrospinal fluid; DOT = directly observed therapy; HBV = hepatitis B virus; HCV = hepatitis C virus; HSV = herpes simplex virus; ICP = intracranial pressure; IFN = interferon; IFN-α = interferon alpha; IGRA = interferon-gamma release assay; IM = intramuscular; IRIS = immune reconstitution inflammatory syndrome; IV = intravenous; LIP = lymphocytic interstitial pneumonia; PCP = pneumocystis pneumonia; PCR = polymerase chain reaction; PK = pharmacokinetic; QID = four times daily; SQ = subcutaneous; TB = tuberculosis; TCA = trichloroacetic acid; TE = toxoplasmic encephalitis; TID = three times daily; TMP-SMX = trimethoprim-sulfamethoxazole; WHO = World Health Organization