What is the appropriate dosing regimen of Bactrim (trimethoprim‑sulfamethoxazole) for adults and children, including adjustments for renal impairment and for Pneumocystis jirovecii pneumonia prophylaxis?

Bactrim (Trimethoprim-Sulfamethoxazole) Dosing Guidelines

For most adult infections, administer 1–2 double-strength tablets (160–320 mg TMP/800–1600 mg SMX) orally every 12 hours; for children over 2 months, use 8–12 mg/kg/day of the trimethoprim component divided every 12 hours, with dose adjustments required when creatinine clearance falls below 30 mL/min. 1

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Standard Adult Dosing

Common Infections

• Urinary tract infections and shigellosis: 1 double-strength tablet every 12 hours for 10–14 days (UTI) or 5 days (shigellosis). 1
• Acute exacerbations of chronic bronchitis: 1 double-strength tablet every 12 hours for 14 days. 1
• Traveler's diarrhea: 1 double-strength tablet every 12 hours for 5 days. 1

MRSA Skin and Soft Tissue Infections

• Purulent cellulitis: 1–2 double-strength tablets orally twice daily for 7–10 days. 2, 3
• Use the higher end of dosing (2 double-strength tablets twice daily) for more severe MRSA infections. 3
• Important caveat: TMP-SMX has excellent activity against CA-MRSA but poorly defined activity against β-hemolytic streptococci, so consider adding coverage for streptococci in nonpurulent cellulitis. 2

Severe/Complicated Infections

• Complicated skin and soft tissue infections: 1–2 double-strength tablets orally or IV equivalent every 12 hours. 2
• MRSA osteomyelitis: Trimethoprim 3.5–4.0 mg/kg per dose every 8–12 hours, typically combined with rifampin for >6 weeks. 3
• MRSA CNS infections (meningitis, brain abscess): Trimethoprim 5 mg/kg per dose every 8–12 hours. 3

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Pediatric Dosing (Children >2 Months)

Standard Infections

• Mild-to-moderate infections (UTI, skin infections): Trimethoprim 8–10 mg/kg/day divided every 12 hours for 7–10 days. 3, 4
• Serious infections (severe MRSA): Trimethoprim 10–12 mg/kg/day divided every 12 hours. 3
• Life-threatening infections: Trimethoprim 15–20 mg/kg/day divided every 6–8 hours (four times daily). 3

Weight-Based Tablet Dosing

For achieving 8 mg/kg trimethoprim per dose every 12 hours: 1

• 10 kg (22 lbs): ½ single-strength tablet
• 20 kg (44 lbs): 1 single-strength tablet
• 30 kg (66 lbs): 1½ single-strength tablets
• 40 kg (88 lbs): 2 single-strength tablets or 1 double-strength tablet

Liquid Formulation

• Suspension concentration: 40 mg trimethoprim per 5 mL. 3
• Use liquid formulation for accurate dosing in children weighing <16 kg. 3
• For a 31 kg child requiring 10 mg/kg/day: total daily dose ≈310 mg TMP, divided into two doses of 155 mg each (approximately 19.4 mL per dose). 3

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Pneumocystis jirovecii Pneumonia (PCP)

Treatment Dosing

• Adults and children: Trimethoprim 15–20 mg/kg/day (sulfamethoxazole 75–100 mg/kg/day) divided every 6 hours for 14–21 days. 1, 3
• Upper limit weight-based dosing: 1
  • 16 kg (35 lbs): 1 tablet every 6 hours
  • 24 kg (53 lbs): 1½ tablets every 6 hours
  • 32 kg (70 lbs): 2 tablets or 1 double-strength tablet every 6 hours
  • 40 kg (88 lbs): 2½ tablets every 6 hours
  • 64 kg (141 lbs): 4 tablets or 2 double-strength tablets every 6 hours
• Transition to oral therapy is appropriate once acute pneumonitis resolves, provided no malabsorption or diarrhea. 3

Prophylaxis Dosing

Adults:

• Standard regimen: 1 double-strength tablet daily. 1
• Alternative regimen: 1 double-strength tablet three times weekly on consecutive days (e.g., Monday-Tuesday-Wednesday). 2, 5

Pediatric (HIV-exposed/infected):

• 150 mg/m²/day trimethoprim with 750 mg/m²/day sulfamethoxazole divided twice daily, given 3 consecutive days per week (maximum 320 mg TMP/1600 mg SMX daily). 3, 1
• Body surface area dosing: 1
  • 0.26 m²: ½ tablet every 12 hours
  • 0.53 m²: 1 tablet every 12 hours
  • 1.06 m²: 2 tablets every 12 hours

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Renal Impairment Dose Adjustments

Prophylaxis Dosing

• CrCl 15–30 mL/min: Reduce dose by 50% (half the usual regimen). 2, 1
• CrCl <15 mL/min: Reduce dose by 50% or use alternative agent. 2
• Hemodialysis patients: 500 mg three times weekly after dialysis for prophylaxis. 5

Treatment Dosing

• CrCl >30 mL/min: Use standard dosing. 1
• CrCl 15–30 mL/min: Use half the usual regimen. 1
• CrCl <15 mL/min: Use is not recommended per FDA label, though clinical guidelines support reduced dosing. 1

For PCP treatment with renal impairment:

• CrCl 10–30 mL/min: Trimethoprim 5 mg/kg every 12 hours (instead of every 6–8 hours). 2, 3
• CrCl <10 mL/min: Trimethoprim 5 mg/kg every 24 hours. 2, 3

Critical point: Failure to adjust dosing for CrCl <30 mL/min markedly increases the risk of adverse effects, particularly hematologic toxicity. 3 Both TMP and SMX accumulate when creatinine clearance falls below 30 mL/min, and metabolites (especially N4-acetyl-SMX) accumulate proportionally to serum creatinine. 6

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Monitoring Requirements

Baseline and Ongoing Monitoring

• Obtain complete blood count with differential and platelet count at treatment initiation and monthly during prolonged therapy to detect neutropenia, thrombocytopenia, and anemia. 3, 4
• Monitor renal function (creatinine clearance and electrolytes) regularly during high-dose therapy to detect drug accumulation and toxicity. 3
• Serum TMP levels should be monitored in patients with severe renal failure; target peak levels are 5–10 μg/mL. 6

Hydration

• Ensure at least 1.5 L of fluid intake daily to prevent crystalluria, especially during high-dose therapy. 2, 3

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Safety Considerations and Contraindications

Absolute Contraindications

• Infants <2 months of age: Not recommended. 1
• Pregnancy at term (third trimester): Avoid use (pregnancy category C/D). 2, 5
• G6PD deficiency: Do not use due to hemolytic anemia risk. 3, 5

Use With Caution

• Severe hepatic impairment: Avoid use. 2
• Renal insufficiency: Requires dose adjustment as outlined above. 3

Drug Interactions

• Methotrexate (treatment doses): Avoid concurrent use due to severe bone marrow suppression risk; lower prophylactic methotrexate doses are generally tolerated. 5
• Warfarin and other anticoagulants: Enhanced anticoagulant effect; monitor INR closely. 3
• Oral hypoglycemics: Increased hypoglycemia risk; monitor blood glucose. 3

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Adverse Reaction Management

Mild Reactions

• Mild rash: Temporarily discontinue Bactrim and restart once the rash resolves; desensitization may be attempted if the drug is essential. 3, 4

Severe/Life-Threatening Reactions

• Stevens-Johnson syndrome, anaphylaxis, urticarial rash, severe hypotension: Permanently discontinue Bactrim and do not rechallenge. 3

Common Adverse Effects

• Rash, pruritus, nausea, leukopenia, and transaminase elevation occur frequently but are rarely life-threatening. 3
• Clostridium difficile–associated disease may occur more frequently with clindamycin than with TMP-SMX. 2
• Adverse reactions occur in approximately 15% of children (lower than adults). 3

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Common Pitfalls and How to Avoid Them

1. Underdosing in pediatric patients: Always calculate doses based on current weight or body surface area; failure to adjust as children grow leads to subtherapeutic levels. 4

2. Inadequate renal dose adjustment: Failure to reduce dosing when CrCl <30 mL/min significantly increases toxicity risk, particularly hematologic and renal adverse effects. 3

3. Insufficient hydration: Inadequate fluid intake during high-dose therapy heightens crystalluria risk; ensure ≥1.5 L daily. 3

4. Overlooking drug interactions: Screen for concurrent methotrexate, warfarin, and oral hypoglycemics before initiating therapy. 3, 5

5. Ignoring β-hemolytic streptococci coverage: In nonpurulent cellulitis, TMP-SMX alone may be inadequate; consider adding β-lactam coverage if streptococcal infection is suspected. 2

6. Using in G6PD deficiency: Always screen for G6PD deficiency before initiating therapy to prevent hemolytic anemia. 3, 5