First-Line Treatment for Uncomplicated Lower UTI in Adult Women
Nitrofurantoin 100 mg orally twice daily for 5 days is the recommended first-line therapy for an adult woman with uncomplicated cystitis who has adequate renal function (eGFR ≥30 mL/min) and no sulfa allergy. 1, 2
Primary Recommendation: Nitrofurantoin
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves 88-93% clinical cure rates and 81-92% bacterial cure rates in uncomplicated UTIs. 2
The 2024 JAMA Network Open guidelines identify nitrofurantoin as the reasonable drug of choice for uncomplicated cystitis based on robust evidence of efficacy and its ability to spare more systemically active agents for other infections. 1
Nitrofurantoin maintains 95-98% susceptibility against E. coli despite over 60 years of use, making it superior to alternatives with higher resistance rates. 2, 3
The 5-day duration balances efficacy with minimizing antibiotic exposure and adverse effects; extending beyond 5 days does not improve outcomes. 2
Alternative First-Line Options When Nitrofurantoin Cannot Be Used
Trimethoprim-sulfamethoxazole (TMP/SMX) 160/800 mg twice daily for 3 days is an acceptable alternative only if local E. coli resistance is <20% and the patient has not used it in the previous 3 months. 1, 2, 4
Fosfomycin trometamol 3 g as a single oral dose is another alternative, though it has modestly lower bacteriological cure rates (63% vs 74% for nitrofurantoin). 2, 5
A 2018 JAMA trial demonstrated that 5-day nitrofurantoin achieved 70% clinical resolution versus 58% for single-dose fosfomycin (12% absolute difference, P=0.004), with microbiologic resolution of 74% versus 63% respectively. 5
Critical Contraindications and Clinical Pitfalls to Avoid
Never use nitrofurantoin if pyelonephritis is suspected (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting, or systemic symptoms), as it does not achieve adequate renal tissue concentrations. 1, 2
Nitrofurantoin is contraindicated when creatinine clearance is <30 mL/min due to reduced efficacy and increased risk of peripheral neuropathy. 2, 6
Do not prescribe TMP/SMX empirically without knowing local resistance rates; treatment failure rates are unacceptably high when resistance exceeds 20%. 2
Avoid using nitrofurantoin for "borderline" upper-tract symptoms—any flank pain or low-grade fever warrants a fluoroquinolone or cephalosporin instead. 2
Diagnostic Criteria for Uncomplicated Lower UTI
Diagnosis requires symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort without fever, flank pain, or systemic signs. 2, 5
The patient must be non-pregnant, have no known urological abnormalities, and have adequate renal function (eGFR ≥30 mL/min). 2
Routine urine cultures are not required for typical uncomplicated cystitis in otherwise healthy women; obtain cultures only if symptoms persist after therapy or recur within 2 weeks. 2
Antimicrobial Stewardship Considerations
Nitrofurantoin is classified by the WHO AWaRe framework as an "Access" antibiotic, reflecting its favorable resistance profile and suitability for first-line empiric therapy. 2
Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for pyelonephritis or complicated UTIs; ciprofloxacin resistance now exceeds 24% in many communities, and overuse accelerates resistance and harms the microbiome. 2, 3
The FDA warns that fluoroquinolones can cause serious adverse effects including tendon rupture, peripheral neuropathy, CNS toxicity, and aortic dissection; they should be reserved for infections where benefits outweigh risks. 2
Common Adverse Effects
The most common side effects of nitrofurantoin are nausea (3%) and headache, with overall adverse event rates of 5.6-34%. 2, 5
Serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003% respectively), occurring mainly with long-term use. 2, 6