What is the recommended treatment and dosage for trimethoprim/sulfamethoxazole (Smz-tmp)?

Trimethoprim-Sulfamethoxazole (TMP-SMX): Treatment and Dosing Recommendations

Primary Indication: PCP Prophylaxis in HIV

For HIV-infected adults and adolescents with CD4+ counts <200 cells/μL, TMP-SMX one double-strength tablet (800mg SMX/160mg TMP) daily is the preferred prophylactic regimen against Pneumocystis pneumonia. 1, 2

Prophylaxis Initiation Criteria

• CD4+ count <200 cells/μL (strongest indication) 1, 2
• History of oropharyngeal candidiasis (regardless of CD4 count) 1, 2
• CD4+ percentage <14% 1, 2
• History of AIDS-defining illness 1, 2
• Consider prophylaxis at CD4+ 200-250 cells/μL when frequent monitoring is not feasible 1

Dosing Regimens for PCP Prophylaxis

Preferred regimen:

• One double-strength tablet (800mg SMX/160mg TMP) once daily 1, 2, 3

Alternative effective regimens:

• One single-strength tablet (400mg SMX/80mg TMP) once daily (better tolerated, equally effective) 1, 2
• One double-strength tablet three times weekly 1, 2

Additional Protective Benefits

• Provides cross-protection against toxoplasmosis at the double-strength daily dose 1, 2
• Reduces common respiratory bacterial infections 1, 2

Treatment of Active PCP

For documented Pneumocystis pneumonia, administer TMP 15-20 mg/kg/day with SMX 75-100 mg/kg/day divided into 3-4 doses every 6 hours for 21 days. 1, 3, 4

Treatment Dosing by Weight (Upper Limit)

• 18-35 lbs (8-16 kg): 1 tablet every 6 hours 3, 4
• 53 lbs (24 kg): 1½ tablets every 6 hours 3, 4
• 70 lbs (32 kg): 2 tablets or 1 double-strength tablet every 6 hours 3, 4
• 88 lbs (40 kg): 2½ tablets every 6 hours 3, 4
• 106 lbs (48 kg): 3 tablets or 1½ double-strength tablets every 6 hours 3, 4

For lower limit dosing (75 mg/kg SMX and 15 mg/kg TMP per 24 hours), administer 75% of the above doses. 3, 4

Route and Duration

• Administer intravenously initially, infused over 1 hour 1
• Switch to oral therapy once acute pneumonitis resolves in patients without malabsorption or diarrhea 1
• Total treatment duration: 21 days 1, 3, 4

Urinary Tract Infections

For uncomplicated UTIs, administer one double-strength tablet every 12 hours for 10-14 days. 3, 4

Pediatric UTI Dosing (≥2 months old)

• 40 mg/kg SMX and 8 mg/kg TMP per 24 hours divided every 12 hours for 10 days 3, 4
• 22-44 lbs (10-20 kg): 1 tablet every 12 hours 3, 4
• 66 lbs (30 kg): 1½ tablets every 12 hours 3, 4
• 88 lbs (40 kg): 2 tablets or 1 double-strength tablet every 12 hours 3, 4

Note: TMP-SMX is no longer recommended as first-line empiric therapy for uncomplicated cystitis due to rising resistance rates; reserve for cases with known susceptibility. 1

Other Indications

Acute Exacerbations of Chronic Bronchitis

• One double-strength tablet every 12 hours for 14 days 3, 4

Shigellosis

• Same dosing as UTI but for only 5 days 3, 4

Traveler's Diarrhea

• One double-strength tablet every 12 hours for 5 days 3, 4

Renal Dose Adjustment

Adjust dosing based on creatinine clearance to prevent toxicity: 3, 4

• CrCl >30 mL/min: Standard dosing
• CrCl 15-30 mL/min: Reduce dose by 50%
• CrCl <15 mL/min: Do not use

Managing Adverse Reactions

For non-life-threatening reactions (mild rash, fever), continue TMP-SMX if clinically feasible rather than switching agents. 1, 2

Desensitization Protocol

• After reaction resolution, reinstitute TMP-SMX with gradual dose escalation 1, 2
• Up to 70% of patients tolerate reinstitution after desensitization 1, 2
• Consider reduced dose or frequency during reintroduction 1

Absolute Contraindications

• Urticarial rash or Stevens-Johnson syndrome: Permanently discontinue; do not rechallenge 1
• Age <2 months: Contraindicated 3, 4

Common Adverse Effects in HIV Patients

• Rash (including erythema multiforme) 1
• Hematologic abnormalities (neutropenia, thrombocytopenia, anemia) 1
• Hepatitis and renal disorders (interstitial nephritis) 1
• Approximately 15% of HIV-infected children experience substantial adverse reactions (lower than adults) 1

Alternative Agents When TMP-SMX Cannot Be Used

If TMP-SMX is not tolerated for PCP prophylaxis, use dapsone 100mg daily as the preferred alternative. 1

Other alternatives include: 1

• Dapsone plus pyrimethamine plus leucovorin (also protects against toxoplasmosis)
• Aerosolized pentamidine via Respirgard II nebulizer
• Atovaquone (expensive but effective)

For PCP treatment failure or intolerance, switch to pentamidine 4 mg/kg/day IV over 60-90 minutes. 1