What is the typical dosage and treatment duration for trimethoprim-sulfamethoxazole (TMP-SMX), also known as Bactrim (sulfamethoxazole/trimethoprim), in adults requiring antibiotics containing sulfa?

Trimethoprim-Sulfamethoxazole (TMP-SMX) Dosing for Adults

For most adult infections requiring sulfa-containing antibiotics, the standard dose is one double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) twice daily, with treatment duration varying from 5 to 14 days depending on the specific infection. 1, 2

Standard Oral Dosing Regimens

Common Infections

• Urinary tract infections: 1 double-strength tablet every 12 hours for 10-14 days 2
• Acute exacerbations of chronic bronchitis: 1 double-strength tablet every 12 hours for 14 days 2
• Traveler's diarrhea: 1 double-strength tablet every 12 hours for 5 days 2
• Shigellosis: 1 double-strength tablet every 12 hours for 5 days 2

Skin and Soft Tissue Infections

• Purulent cellulitis (MRSA suspected): 1-2 double-strength tablets twice daily for typically 7 days based on clinical response 1
• Critical caveat: TMP-SMX has poor activity against beta-hemolytic streptococci and should NOT be used alone for non-purulent cellulitis where streptococci are likely pathogens 1
• Mixed aerobic-anaerobic infections: Do not use as monotherapy; lacks anaerobic coverage and requires combination therapy 1

Pneumocystis Pneumonia

• Treatment dose: 75-100 mg/kg/day sulfamethoxazole and 15-20 mg/kg/day trimethoprim, divided every 6 hours for 14-21 days 2
  • For an 88 kg (176 lb) adult: 2 double-strength tablets every 6 hours 2
• Prophylaxis dose: 1 double-strength tablet once daily 3, 2
  • This is the preferred regimen over aerosol pentamidine for patients without history of serious sulfa reactions 3

Native Vertebral Osteomyelitis

• Second-line agent: 1-2 double-strength tablets twice daily 3
• Not recommended for staphylococcal osteomyelitis but may be used for Enterobacteriaceae and other susceptible gram-negative organisms 3
• May require monitoring of sulfamethoxazole levels 3

Intravenous Dosing

Severe Infections

• Standard IV dose: Trimethoprim 320 mg/day and sulfamethoxazole 1,600 mg/day, divided into 2 doses every 12 hours 4
• CNS infections or severe bacteremia: 5 mg/kg/dose (based on trimethoprim) IV every 8-12 hours 1
• Complicated infections: 8-12 mg/kg/day (based on trimethoprim component) divided into 4 doses IV 1

Renal Dose Adjustment

Dosing must be adjusted for impaired renal function 2:

• Creatinine clearance >30 mL/min: Standard dosing
• Creatinine clearance 15-30 mL/min: Half the usual regimen
• Creatinine clearance <15 mL/min: Use not recommended 2

Critical Safety Considerations

Absolute Contraindications

• Third trimester pregnancy: Risk of kernicterus 1
• Nursing mothers: Risk to infant 1
• Infants <2 months of age: Risk of kernicterus and altered drug metabolism 3, 4, 2
• Known sulfa allergies: Avoid entirely 1

Monitoring Requirements

• Hematologic: Monitor for leukopenia, thrombocytopenia, and blood dyscrasias 4
• Dermatologic: Watch for rash, Stevens-Johnson syndrome (rare: 1/200,000 courses) 3
• Gastrointestinal: Nausea and vomiting are common 4
• Renal: Maintain adequate fluid intake to prevent crystalluria and renal stones 4

High-Risk Populations Requiring Caution

• Impaired hepatic function 4
• Folate deficiency 4
• G6PD deficiency: Risk of hemolytic anemia, though rarely reported 3

Emerging Safety Concern

• Severe ARDS: A recently identified life-threatening adverse reaction has been reported in young, previously healthy patients receiving ≥6 days of treatment-dose TMP-SMX (not prophylaxis), with mortality approaching 40% 5
• This condition is associated with HLA-B07:02 and HLA-C07:02 alleles 5
• Consider this diagnosis in unexplained severe respiratory failure developing during TMP-SMX therapy 5

Adverse Reaction Management

HIV-infected adults experience more frequent and severe reactions (40-65%) compared to HIV-infected children (15%) 3:

• Most common: Pruritus, rash, leukopenia, transaminase elevation, nausea 3
• Severe exfoliative rashes (Stevens-Johnson syndrome) are rare 3
• Some experts support rechallenge after mild reactions, as ACTG 021 showed similar severe reaction rates (32% vs 26%) regardless of prior mild intolerance 3
• Desensitization protocols may allow some patients with previous reactions to tolerate TMP-SMX 3