When to prescribe Bactrim (trimethoprim-sulfamethoxazole) vs Macrobid (nitrofurantoin) for an uncomplicated urinary tract infection (UTI) in an otherwise healthy adult, considering factors such as recurrent UTIs, pregnancy, and impaired renal function?

When to Prescribe Bactrim vs Macrobid for UTI

For uncomplicated UTIs in otherwise healthy adults, nitrofurantoin (Macrobid) 100 mg twice daily for 5 days is the preferred first-line agent over trimethoprim-sulfamethoxazole (Bactrim) due to lower resistance rates, minimal collateral damage to normal flora, and superior efficacy in most clinical settings. 1

First-Line Treatment Selection Algorithm

Choose Nitrofurantoin (Macrobid) When:

• Standard uncomplicated cystitis in women with typical symptoms (dysuria, frequency, urgency, suprapubic pain) 1, 2
• No suspicion of pyelonephritis (absence of fever, flank pain, or systemic symptoms) 1, 2
• Creatinine clearance ≥30 mL/min 2, 3
• Not pregnant in third trimester 3
• Local E. coli resistance to nitrofurantoin <10% 3

Dosing: 100 mg twice daily for 5 days 1, 2

Choose Bactrim (TMP-SMX) When:

• Local E. coli resistance to TMP-SMX is <20% AND patient has not used it in the previous 3 months 1
• Suspected pyelonephritis (fever, flank pain, systemic symptoms) where nitrofurantoin is contraindicated 1
• Renal impairment with CrCl <30 mL/min where nitrofurantoin cannot be used 2, 3
• Men with uncomplicated UTI (7-day course preferred over 3 days) 4

Dosing: 160/800 mg (one DS tablet) twice daily for 3 days in women, 7 days in men 1, 5, 4

Critical Contraindications and Caveats

Nitrofurantoin Should NOT Be Used For:

• Suspected or confirmed pyelonephritis - does not achieve adequate renal tissue concentrations 1, 2
• CrCl <30 mL/min - increased risk of peripheral neuropathy and treatment failure 2, 3
• Third trimester pregnancy (risk of hemolytic anemia in newborn) 3
• Infants <4 months of age 3

Bactrim Should NOT Be Used For:

• Local resistance rates ≥20% - unacceptably high treatment failure rates 1, 3
• Recent use within 3 months - increases resistance risk 1
• Severe sulfa allergy 5
• Pregnancy near term (risk of kernicterus) 5

Special Clinical Scenarios

Recurrent UTIs:

• Both agents can be used for prophylaxis, but nitrofurantoin is preferred due to lower resistance development 1, 3
• Obtain urine culture before treatment to guide antibiotic selection 1
• Do NOT treat asymptomatic bacteriuria 1

Pregnancy:

• First and second trimester: Both nitrofurantoin and TMP-SMX can be used, though nitrofurantoin is generally preferred 3
• Third trimester: Avoid both agents; nitrofurantoin contraindicated, TMP-SMX should be avoided 3, 5

Renal Impairment:

• CrCl 15-30 mL/min: Use half-dose Bactrim; avoid nitrofurantoin 2, 5
• CrCl <15 mL/min: Avoid both agents 2, 5

Men with UTI Symptoms:

• Always obtain urine culture before treatment 4
• Consider prostatitis or urethritis as alternative diagnoses 4
• Use 7-day courses (not 3 days) for either agent 4

Resistance Considerations

The critical distinction: Nitrofurantoin maintains excellent activity against E. coli despite 60+ years of use, while TMP-SMX resistance now exceeds 20% in many communities, making it unsuitable for empiric therapy in those areas 1, 6, 7. Multiple international guidelines now rank nitrofurantoin before TMP-SMX in treatment hierarchies due to antimicrobial stewardship concerns 1, 3.

Common Pitfalls to Avoid

• Do not use nitrofurantoin if any suspicion of upper tract involvement - this is the most common prescribing error, as it will not treat pyelonephritis effectively 1, 2
• Do not prescribe TMP-SMX empirically without knowing local resistance rates - treatment failure rates are unacceptably high when resistance exceeds 20% 1
• Do not extend nitrofurantoin beyond 7 days for acute cystitis - increases risk of serious pulmonary and hepatic toxicity 1, 2
• Do not obtain routine post-treatment cultures in asymptomatic patients - this promotes unnecessary antibiotic use 1