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Toxoplasmosis

• Toxoplasma gondii (treatment)

• 1. Lymphadenopathic toxoplasmosis

• Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.

• 2. Ocular disease

• 2.1 Adults

• Preferred regimen: Pyrimethamine 100 mg PO for 1 day as a loading dose, then 25 to 50 mg/day AND Sulfadiazine 1 g PO qid AND folinic acid (Leucovorin 5-25 mg PO with each dose of Pyrimethamine

• 2.2 Pediatric

• Preferred regimen: Pyrimethamine 2 mg/kg PO first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg PO bid AND folinic acid (Leucovorin 7.5 mg/day PO ) for 4 to 6 weeks followed by reevaluation of the patient's condition
• Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
• Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.

• 3. Maternal and fetal infection

• 3.1 First and early second trimesters

• Preferred regimen: Spiramycin is recommended

• 3.2 Late second and third trimesters

• Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.

• 3.3 Infant

• Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine, Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.

• 4. Toxoplasma gondii Encephalitis in AIDS

• 4.1 Treatment for acute infection

• 4.1.1 Patients with weight <60 kg
• Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 50 mg PO qd AND Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO qd,
• 4.1.2 Patients with weight ≥60 kg

• Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 75 mg PO once daily AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO once daily. Leucovorin dose can be increased to 50 mg daily or BID.
• Alternative regimen (1): Pyrimethamine AND Leucovorin AND Clindamycin 600 mg IV/ PO q6h
• Alternative regimen (2): TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO BID
• Alternative regimen (3): Atovaquone 1500 mg PO bid AND Pyrimethamine AND Leucovorin
• Alternative regimen (4): Atovaquone1500 mg PO bid AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
• Alternative regimen (5): Atovaquone 1500 mg PO bid
• Alternative regimen (6): Pyrimethamine AND Leucovorin AND Azithromycin 900–1200 mg PO daily
• Note: Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

• 4.2 Chronic maintenance therapy

• Preferred regimen: Pyrimethamine 25–50 mg PO qd AND sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
• Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO qd
• Alternative regimen (2): TMP-SMX DS 1 tablet bid
• Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
• Alternative regimen (4): Atovaquone 750–1500 mg PO bid
• Alternative regimen (5): Sulfadiazine 2000–4000 mg PO bid/qid
• Alternative regimen (6): Atovaquone 750–1500 mg PO bid Pyrimethamine and Leucovorin doses are the same as for preferred therapy
• Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.

• Toxoplasma gondii (prophylaxis)

• 1. Prophylaxis to prevent first episode of encephalitis in AIDS

• 1.1 Indications

• Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
• Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.

• 1.2 Prophylactic therapy

• Preferred regimen: TMP-SMX 1 DS PO daily
• Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
• Alternative regimen (2): TMP-SMX 1 SS PO qd
• Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg AND Leucovorin 25 mg) PO weekly
• Alternative regimen (4): Dapsone 200 mg AND Pyrimethamine 75 mg AND Leucovorin 25 mg PO weekly
• Alternative regimen (5): Atovaquone 1500 mg PO qd
• Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg AND Leucovorin 10 mg PO qd

varicella zoster

• 1. Varicella zoster

• 1.1 Non Immunocompromised person

• Preferred regimen (1): Acyclovir 500 mg PO five times daily for 7-10 days
• Preferred regimen (2):Famciclovir 500 mg PO tid daily for 7 days
• Preferred regimen (3):Valacyclovir 1 g PO tid daily for 7 days
• Preferred regimen (4): Brivudin125 mg PO qd daily for 7 days

• 1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications

• Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
• Preferred regimen (2):Foscarnet 40 mg/ kg IV q8h until lesions are healed

• Note (1): Brivudin is not available in USA and has not been approved by FDA
• Note (2): Foscarnet is not approve by FDA

• Treatment of VZV complications

• HZ ophthalmicus
• Treatment includes the following
• (1) Famciclovir or Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with IV Acyclovir given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences

(2) pain medications,

(3) cool to tepid wet compresses (if tolerated);

(4) antibiotic ophthalmic ointment administered bid (e.g.Bacitracin-Polymyxin), to protect the ocular surface;

(5) topical steroids (e.g., 0.125%–1% Prednisolone 2–6 times daily) prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis;

(6) no topical antivirals, because they are ineffective;

(7) mydriatic/cycloplegia as needed for iritis (e.g., 5% Homatropine bid

(8) ocular pressure–lowering drugs given as needed for glaucoma (e.g., Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning). Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit. The dosage is commonly 20 mg of Prednisone administered (together with an oral antiviral agent) PO tid for 4 days,bid for 6 days, and then once daily every morning for 4 day

• VZV retinitis
• Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks

Treatment of Varicella Infections

Primary Varicella Infection (Chickenpox) Uncomplicated Cases Preferred Therapy: Valacyclovir 1 g PO TID (AII), or Famciclovir 500 mg PO TID (AII)

Alternative Therapy: Acyclovir 800 mg PO 5 times daily (BII)

Duration: 5–7 days

Severe or Complicated Cases: Acyclovir 10–15 mg/kg IV q8h for 7–10 days (AIII) May switch to oral famciclovir, valacyclovir, or acyclovir after defervescence if no evidence of visceral involvement is evident (BIII)

Herpes Zoster (Shingles) Acute Localized Dermatomal Preferred Therapy: Valacyclovir 1000 mg PO TID (AII), or Famciclovir 500 mg PO TID (AII)

Alternative Therapy: Acyclovir 800 mg PO 5 times daily (BII)

Duration: 7–10 days, longer duration should be considered if lesions resolve slowly

Extensive Cutaneous Lesion or Visceral Involvement Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident (AII) Switch to oral therapy (valacyclovir 1 g TID, famciclovir 500 mg TID, or acyclovir 800 mg PO 5 times daily)—to complete a 10–14 day course, when formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving (BIII)

PORN Involvement of an experienced ophthalmologist is strongly recommended (AIII) Ganciclovir 5 mg/kg and/or foscarnet 90 mg/kg IV q12h plus ganciclovir 2 mg/0.05mL and/or foscarnet 1.2 mg/0.05mL intravitreal twice weekly (AIII) Optimize ART regimen (AIII) Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with ophthalmologist.

Note: ganciclovir ocular implants are no longer commercially available ARN Acyclovir 10-15 mg/kg IV q8h for 10–14 days, followed by valacyclovir 1 g PO TID for 6 weeks PLUS ganciclovir 2 mg/0.05mL intravitreal twice weekly X 1-2 doses (AIII) Involvement of an experienced ophthalmologist is strongly recommended (AIII) Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with ophthalmologist.

Influenza

• Influenza virus Return to Top

• 1. Adults

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg bid
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid
• Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
• Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs

• 2. Children

• 2.1 < 1 yr

• Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose bid

• 2.2 > 1 yr

• 2.2.1 ≤ 15 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 30 mg bid

• 2.2.2 > 15 to 23 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 45 mg bid

• 2.2.3 > 23 to 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 60 mg bid

• 2.2.4 > 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 75 mg bid
• Note: Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid may be considered for children > 7 yrs old

• Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis
• Oral Oseltamivir
• Creatinine clearance 61 to 90 mL/min-75 mg twice a day
• Creatinine clearance 31 to 60 mL/min-30 mg twice a day
• Creatinine clearance 10 to 30 mL/min-30 mg once daily
• ESRD Patients on Hemodialysis
• Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
• ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange

• Intravenous Peramivir (single dose)
• Creatinine clearance >50 mL/min-600mg
• Creatinine clearance 30 to 49 mL/min-200mg
• Creatinine clearance 10 to 29 mL/min-100mg
• ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance

Children- < 1 yr: 3 mg/kg/dose twice daily > 1 yr: dose depends on weight. ≤ 15 kg: 30 mg twice a day > 15 to 23 kg: 45 mg twice a day > 23 to 40 kg: 60 mg twice a day > 40 kg: 75 mg twice a day.

Zanamivir (Relenza®) Adults 10 mg (two 5-mg inhalations) twice daily

For children > 7 yrs old. 10 mg (two 5-mg inhalations) twice daily

Peramivir (Rapivab®) Adults 600 mg IV for 15-30 minutes (single dose)