What is the recommended dosage of Cotrimoxazole (trimethoprim/sulfamethoxazole) for a patient with pneumonia, assuming normal renal function and no known allergies or interactions?

Cotrimoxazole Dosing for Pneumonia

For community-acquired pneumonia in adults with normal renal function, cotrimoxazole is not a first-line agent and should only be used for specific pathogens like Pneumocystis jirovecii pneumonia (PCP), where the recommended dose is 15-20 mg/kg/day of trimethoprim (TMP) component divided every 6-8 hours for 14-21 days. 1

Type of Pneumonia Determines Dosing

Pneumocystis jirovecii Pneumonia (PCP) - Treatment Dose

• Standard treatment regimen: 75-100 mg/kg/day sulfamethoxazole (SMZ) and 15-20 mg/kg/day TMP, divided into 4 doses given every 6 hours for 14-21 days 1
• Practical dosing for adults: This translates to approximately 2 double-strength tablets (800mg SMZ/160mg TMP each) every 6 hours, or 8 double-strength tablets total per day for severe cases 1
• Initial IV therapy preferred: For hospitalized patients, start with IV formulation at 15-20 mg/kg/day TMP, then transition to oral once clinical improvement occurs (typically after 4 days) 2
• Duration: Continue for minimum 14 days, extending to 21 days for severe cases or immunocompromised patients 1

Burkholderia pseudomallei (Melioidosis) - Eradication Phase

• Weight-based dosing 3:
  • <40 kg: 160/800 mg (1 double-strength tablet) every 12 hours
  • 40-60 kg: 240/1200 mg (1.5 double-strength tablets) every 12 hours

  • 60 kg: 320/1600 mg (2 double-strength tablets) every 12 hours

• Add folic acid: 0.1 mg/kg up to 5 mg daily to prevent antifolate toxicity 3
• Duration: Extended eradication phase after initial intensive therapy 3

Community-Acquired Bacterial Pneumonia

Cotrimoxazole is NOT recommended as first-line therapy for typical community-acquired pneumonia - β-lactam antibiotics with or without macrolides are preferred 3. Cotrimoxazole should only be considered for:

• Documented MRSA pneumonia (alternative agent): 5 mg/kg/dose IV every 8-12 hours 3
• Specific susceptible pathogens when first-line agents have failed 3

Renal Dose Adjustments

Critical for preventing toxicity, as both TMP and SMZ accumulate in renal insufficiency 1, 4:

• CrCl >30 mL/min: Standard dosing, no adjustment needed 1
• CrCl 15-30 mL/min: Reduce dose by 50% (use half the usual regimen) 1
• CrCl <15 mL/min: Use not recommended 1
• Alternative calculation: Increase dosing interval (in hours) to 12 times the serum creatinine level in mg/dL, with maximum interval of 48 hours 5
• CRRT patients: May require dose increase for sulfamethoxazole component, as CRRT increases SMZ clearance but not TMP clearance 4

Monitoring and Safety

Therapeutic Drug Monitoring

• Target peak TMP levels: 5-10 mcg/mL for optimal efficacy 5
• Monitor in renal failure: Check TMP levels and N-acetyl-SMZ levels, as the metabolite accumulates significantly with reduced eGFR 5, 4

Hematologic Toxicity

• Obtain baseline CBC before initiating therapy 6, 7
• Monitor CBC monthly during prolonged therapy to detect thrombocytopenia, leukopenia, or anemia 6, 7
• Higher risk with: Elevated serum TMP levels and longer treatment duration 5

Contraindications

• G6PD deficiency: Absolute contraindication due to hemolytic anemia risk 6, 7
• Pregnancy at term: Avoid use per ACOG recommendations 6
• Sulfa allergy: Contraindicated 8

Common Pitfalls to Avoid

• Do not use standard UTI dosing (160/800 mg twice daily) for pneumonia - this is inadequate for PCP and most pneumonias requiring cotrimoxazole 1
• Do not delay switching to alternative therapy: If no clinical improvement by day 4-6 of PCP treatment, change to pentamidine rather than continuing ineffective therapy 2
• Do not forget folic acid supplementation when treating melioidosis or in patients at risk for folate deficiency 3
• Do not use treatment doses with concurrent methotrexate - severe bone marrow suppression can occur; only prophylactic doses are safe 6, 7
• Ensure adequate absorption: Oral therapy may fail in patients with GI malabsorption; use IV route initially for severe pneumonia 2