Drug of Choice for Uncomplicated Adult Urinary Tract Infection (Cystitis)
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the preferred first-line treatment for uncomplicated cystitis in otherwise healthy adult women. 1, 2, 3
First-Line Treatment Options
Nitrofurantoin 100 mg twice daily for 5 days achieves clinical cure rates of 88–93% and bacteriologic cure rates of 81–92%, with minimal resistance (<10% globally) and limited collateral damage to normal flora. 1, 2, 3
Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days is appropriate only when local E. coli resistance is documented to be <20% and the patient has not received this agent in the preceding 3–6 months. 1, 2
Fosfomycin trometamol 3 g as a single oral dose provides clinical cure rates of 90–91% but lower microbiologic cure rates (78–80%) compared to nitrofurantoin, making it a convenient alternative when multi-day regimens are problematic. 1, 2, 4
Critical Resistance Threshold for TMP-SMX
When E. coli is susceptible to TMP-SMX, clinical cure rates reach 90–100%; however, when the organism is resistant, cure rates plummet to 41–54%, making treatment failure the expected outcome. 1, 2
The 20% resistance threshold is derived from expert opinion integrating clinical outcomes, in-vitro data, and mathematical modeling; above this level, TMP-SMX should not be used empirically. 1, 2
Reserve (Second-Line) Agents
Fluoroquinolones (ciprofloxacin 250 mg twice daily for 3 days or levofloxacin) achieve bacteriologic eradication rates of 93–97% but should be reserved for pyelonephritis or when first-line agents are contraindicated, due to FDA warnings regarding tendon rupture, peripheral neuropathy, and aortic dissection. 1, 2, 5
Oral β-lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) for 3–7 days demonstrate inferior efficacy and higher adverse-event rates compared to nitrofurantoin or TMP-SMX; they should be used only when first-line agents cannot be used. 1, 3
Agents to Avoid
- Amoxicillin or ampicillin alone should never be used empirically because worldwide E. coli resistance exceeds 30%, resulting in poor therapeutic outcomes. 1, 3
Treatment Duration by Sex
Women: 3 days for TMP-SMX or 5 days for nitrofurantoin is sufficient for uncomplicated cystitis. 1, 2, 6
Men: 7 days of therapy is required for uncomplicated cystitis because short-course regimens that are effective in women are inadequate for men. 2
Contraindications to Nitrofurantoin
Suspected pyelonephritis (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting) is an absolute contraindication because nitrofurantoin does not achieve adequate renal tissue concentrations. 2, 3, 7
Creatinine clearance <30 mL/min contraindicates nitrofurantoin due to reduced efficacy and increased risk of peripheral neuropathy, pulmonary toxicity, and hepatotoxicity. 2, 7
Risk Factors Predicting TMP-SMX Resistance
Recent TMP-SMX exposure (within the preceding 3–6 months) independently predicts resistant infections and should prompt avoidance of empiric TMP-SMX. 2
Recent international travel (outside the United States within the preceding 3–6 months) is associated with higher rates of TMP-SMX-resistant uropathogens and similarly contraindicates empiric use. 2
Common Pitfalls to Avoid
Using nitrofurantoin for "borderline" upper-tract symptoms (e.g., mild flank pain or low-grade fever) is ineffective because the drug does not reach therapeutic concentrations in renal tissue. 2, 7
Prescribing TMP-SMX without local susceptibility data is discouraged, especially in regions where resistance exceeds the 20% threshold; hospital antibiograms often overestimate community resistance because they reflect complicated infections. 2
Empiric ciprofloxacin for simple cystitis contributes to rising resistance (now approximately 24% in many communities) and should be avoided unless resistance data specifically support its use. 2, 7
Treating asymptomatic bacteriuria in non-pregnant, non-catheterized patients promotes resistance without clinical benefit. 2, 3
Diagnostic Criteria
Diagnosis requires symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort without fever, flank pain, nausea/vomiting, or costovertebral angle tenderness. 3, 7
Routine urine culture is not required for typical uncomplicated cystitis in otherwise healthy women; it should be reserved for atypical presentations, treatment failures, or recurrence within 2–4 weeks. 2, 3
Management of Treatment Failure
- If symptoms have not resolved by day 3 of therapy or recur within 2 weeks, obtain a urine culture immediately and switch to a different antibiotic class for a full 7-day course. 2