Treatment of Acute Uncomplicated Cystitis
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the recommended first-line treatment for acute uncomplicated cystitis in premenopausal, non-pregnant women. 1
First-Line Treatment Options
The Infectious Diseases Society of America identifies three appropriate first-line agents for acute uncomplicated cystitis 1:
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is preferred due to minimal resistance patterns and limited collateral damage to normal flora, with clinical cure rates of 88-93% and bacterial cure rates of 81-92% 1, 2
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is appropriate ONLY when local resistance rates are documented to be <20% or when susceptibility testing confirms the organism is susceptible 1, 3
Fosfomycin trometamol 3 g single dose is an alternative first-line option with minimal resistance, though microbiological cure rates may be slightly lower (78%) compared to nitrofurantoin (86%) 1, 3
Why Nitrofurantoin is Preferred
Nitrofurantoin demonstrates equivalent efficacy to both trimethoprim-sulfamethoxazole and fluoroquinolones in head-to-head trials 4, 2:
In a randomized trial comparing 5-day nitrofurantoin to 3-day trimethoprim-sulfamethoxazole, clinical cure at 30 days was 84% vs 79% respectively (difference not statistically significant) 2
Early clinical cure rates with nitrofurantoin (93%) matched those of ciprofloxacin (95%) and trimethoprim-sulfamethoxazole (95%) 4
Nitrofurantoin maintains effectiveness even as trimethoprim-sulfamethoxazole resistance increases globally 1, 3
Critical Caveat About Trimethoprim-Sulfamethoxazole
The 20% resistance threshold is absolute - trimethoprim-sulfamethoxazole shows dramatically reduced efficacy against resistant organisms with clinical cure rates of only 41-54% for resistant strains versus 84-88% for susceptible strains 1. In the landmark study by Gupta et al., only 7 of 17 women (41%) with trimethoprim-sulfamethoxazole-resistant isolates achieved clinical cure compared to 84% with susceptible isolates (P<0.001) 2.
Agents to Reserve or Avoid
Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved as alternative agents despite their high efficacy in 3-day regimens, due to their propensity for promoting resistance and collateral damage to normal flora 1, 3. These agents should be preserved for more serious infections like pyelonephritis.
β-lactam agents (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) in 3-7 day regimens have inferior efficacy and more adverse effects compared to first-line agents, and should only be used when first-line agents cannot be tolerated 4, 1.
Amoxicillin or ampicillin monotherapy should never be used empirically due to poor efficacy and very high prevalence of antimicrobial resistance worldwide 4, 1.
Treatment Duration Matters
The specific durations are evidence-based and should not be shortened 1:
- Nitrofurantoin requires 5-7 days (not 3 days)
- Trimethoprim-sulfamethoxazole is effective at 3 days
- Fluoroquinolones are effective at 3 days
- β-lactams require 3-7 days
Common Pitfalls to Avoid
Do not order urine cultures routinely for straightforward acute uncomplicated cystitis in otherwise healthy premenopausal women - diagnosis can be made clinically based on frequency and dysuria 5. Cultures are indicated only if symptoms don't resolve by end of treatment, recur within 2 weeks, or if the patient has atypical symptoms 5.
Do not use short-course nitrofurantoin regimens in men - the guidelines for uncomplicated cystitis (3-5 day regimens) apply only to premenopausal, non-pregnant women 6. Men require 7-day fluoroquinolone therapy due to potential prostatic involvement 6.
Do not withhold treatment while awaiting culture results in symptomatic patients - immediate antimicrobial therapy is superior to delayed treatment or symptom management with NSAIDs alone 3.