What are the first-line antibiotics for treating uncomplicated acute cystitis?

First-Line Antibiotics for Uncomplicated Acute Cystitis

Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is the recommended first-line therapy for uncomplicated acute cystitis due to minimal resistance and limited collateral damage, with efficacy comparable to trimethoprim-sulfamethoxazole. 1

First-Line Treatment Options

• Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is recommended as first-line therapy with clinical cure rates of 88-93% and bacterial cure rates of 81-92% 1

• Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) is an appropriate first-line therapy only when local resistance rates of uropathogens are known to be <20% or the infecting strain is confirmed susceptible 2, 1

• Fosfomycin trometamol (3 g in a single dose) is an appropriate choice due to minimal resistance and propensity for collateral damage, though it may have inferior efficacy compared with standard short-course regimens 2

• Pivmecillinam (400 mg twice daily for 3-7 days) is recommended in regions where available (primarily European countries, not available in North America) 2, 1

Treatment Algorithm

1. First assess local resistance patterns:

   • If local E. coli resistance to trimethoprim-sulfamethoxazole is <20%:
     • Either nitrofurantoin or trimethoprim-sulfamethoxazole can be used as first-line therapy 2
   • If local E. coli resistance to trimethoprim-sulfamethoxazole is ≥20%:
     • Nitrofurantoin should be the preferred first-line agent 2, 1

2. Consider patient-specific factors:

   • For patients with renal insufficiency (CrCl <30 ml/min): avoid nitrofurantoin 3
   • For patients with CrCl 30-60 ml/min: nitrofurantoin can still be effective 3

Alternative Treatment Options

• Fluoroquinolones (ofloxacin, ciprofloxacin, levofloxacin) are highly effective in 3-day regimens but should be reserved as alternative agents due to their propensity for collateral damage and the need to preserve them for more serious infections 2, 1

• β-Lactam agents (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) in 3-7 day regimens should only be used when first-line agents cannot be used, as they generally have inferior efficacy and more adverse effects 2

• Amoxicillin-clavulanate has been shown to be less effective than ciprofloxacin for acute uncomplicated cystitis, with clinical cure rates of 58% versus 77% respectively 4

Treatments to Avoid

• Amoxicillin or ampicillin should not be used for empirical treatment due to poor efficacy and high prevalence of antimicrobial resistance worldwide 2, 1

Treatment Duration

• Nitrofurantoin requires 5 days of treatment 2, 1
• Trimethoprim-sulfamethoxazole is effective with 3 days of treatment 2, 5
• Fosfomycin is administered as a single 3g dose 2, 1
• Fluoroquinolones are effective in 3-day regimens 2, 1

Common Pitfalls and Caveats

• Despite guideline recommendations, fluoroquinolones remain the most commonly prescribed antibiotics for uncomplicated cystitis (51.6% of prescriptions in one study), indicating low adherence to guidelines 6

• Treatment durations are frequently longer than recommended, with extended durations prescribed for trimethoprim-sulfamethoxazole, nitrofurantoin, and fluoroquinolones in 82%, 73%, and 71% of prescriptions respectively 6

• Urine cultures are not routinely recommended for uncomplicated cystitis but should be obtained for suspected pyelonephritis, symptoms that do not resolve or recur within 2-4 weeks after treatment, or atypical presentations 7

• For recurrent uncomplicated cystitis, the strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode, initiated as soon as clinical symptoms appear 8