What is the recommended dosage and treatment plan for trimethoprim (TMP) for urinary tract infections (UTIs)?

Trimethoprim-Sulfamethoxazole Dosing for Urinary Tract Infections

For acute uncomplicated cystitis in women, prescribe trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) twice daily for 3 days, but only if local E. coli resistance rates are below 20%. 1, 2

Standard Dosing Regimens

Uncomplicated Cystitis in Women

• 160 mg trimethoprim/800 mg sulfamethoxazole twice daily for 3 days is the recommended first-line regimen 3, 1, 2
• This 3-day course achieves clinical cure rates of 90-100% when the pathogen is susceptible 1, 2
• Bacterial cure rates similarly range from 85-100% with the 3-day regimen 3, 2

Uncomplicated UTI in Men

• 160 mg trimethoprim/800 mg sulfamethoxazole twice daily for 7 days is required due to higher risk of prostatic involvement 1

Pyelonephritis

• 160 mg trimethoprim/800 mg sulfamethoxazole twice daily for 14 days, but only after confirming susceptibility 1

Critical Resistance Threshold

The 20% resistance threshold is non-negotiable for empiric therapy. When local E. coli resistance to trimethoprim-sulfamethoxazole exceeds 20%, you must choose alternative agents 1, 2. The evidence demonstrates dramatic efficacy drops when treating resistant organisms:

• Clinical cure rates plummet from 84-90% to only 41-54% with resistant pathogens 3, 1
• Microbiological cure similarly drops from 86-91% to 42% 3

Alternative First-Line Agents

When trimethoprim-sulfamethoxazole cannot be used due to resistance patterns or contraindications, select from these alternatives 1, 2:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days 2
• Fosfomycin trometamol 3 g as a single dose 2
• Pivmecillinam 400 mg three times daily for 3-5 days (where available) 2

Important Clinical Caveats

Pregnancy Considerations

• Avoid trimethoprim-sulfamethoxazole in the last trimester of pregnancy due to potential fetal complications 1

Duration Matters for Adverse Events

• Each additional day of treatment beyond the recommended 3-day course increases antibiotic-associated adverse events by 5% without improving efficacy 1
• The 3-day regimen produces adverse effects in 1.4-31% of patients compared to 15-38% with 10-day courses 2

Common Side Effects

• Rash, urticaria, nausea, vomiting, and hematologic abnormalities occur with trimethoprim-sulfamethoxazole 1
• These side effects are generally less frequent than with the combination compared to sulfonamides alone 4

Agents to Avoid

• Never use amoxicillin or ampicillin empirically for UTI due to poor efficacy and high resistance rates 2

Algorithmic Approach to Treatment Selection

1. Confirm diagnosis: Uncomplicated cystitis with >10^5 CFU/mL and UTI symptoms
2. Check local resistance data: Is E. coli resistance to trimethoprim-sulfamethoxazole <20%?
   • Yes: Prescribe trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days 1, 2
   • No: Choose nitrofurantoin, fosfomycin, or pivmecillinam 1, 2
3. Special populations:
   • Men: Extend to 7 days 1
   • Pyelonephritis: Extend to 14 days and confirm susceptibility 1
   • Third trimester pregnancy: Avoid trimethoprim-sulfamethoxazole entirely 1