What is the choice of drug for treating uncomplicated acute cystitis?

First-Line Treatment for Uncomplicated Acute Cystitis

Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is the recommended first-line treatment for uncomplicated acute cystitis due to its high efficacy and minimal resistance patterns. 1, 2

Treatment Algorithm for Uncomplicated Acute Cystitis

First-Line Options (in order of preference):

1. Nitrofurantoin monohydrate/macrocrystals

   • Dosage: 100 mg twice daily for 5 days
   • Clinical efficacy: 93% (84-95%)
   • Microbiological efficacy: 88% (86-92%)
   • Common side effects: Nausea, headache 1
   • Contraindication: Should not be used in patients with CrCl <30 mL/min 2

2. Trimethoprim-sulfamethoxazole (TMP-SMX)

   • Dosage: 160/800 mg (one double-strength tablet) twice daily for 3 days
   • Clinical efficacy: 93% (90-100%)
   • Microbiological efficacy: 94% (91-100%)
   • Common side effects: Rash, urticaria, nausea, vomiting, hematologic effects 1
   • Only use when local resistance rates are <20% 2, 3

3. Fosfomycin trometamol

   • Dosage: 3 g single dose
   • Clinical efficacy: 91%
   • Microbiological efficacy: 80% (78-83%)
   • Common side effects: Diarrhea, nausea, headache 1
   • Note: Slightly inferior efficacy compared to other regimens 2, 4

Second-Line Options:

• Fluoroquinolones (ofloxacin, ciprofloxacin, levofloxacin)

  • 3-day regimens
  • Clinical efficacy: 90% (85-98%)
  • Microbiological efficacy: 91% (81-98%)
  • Should be reserved for more serious infections due to:
    • Propensity for collateral damage to normal flora
    • FDA warnings about serious side effects
    • Need to preserve effectiveness for more serious infections 1, 2

• β-Lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil)

  • 3-7 day regimens
  • Clinical efficacy: 89% (79-98%)
  • Microbiological efficacy: 82% (74-98%)
  • Not recommended as first-line due to inferior efficacy and more adverse effects 1, 2

Evidence Comparison

The 2011 Infectious Diseases Society of America (IDSA) guidelines strongly support nitrofurantoin as a first-line agent 1. Clinical trials demonstrate nitrofurantoin achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92% 1. When compared directly to fosfomycin, nitrofurantoin showed superior microbiological cure rates (86% vs. 78%, p=0.02) 1.

FDA data shows fosfomycin is equivalent to nitrofurantoin but inferior to ciprofloxacin and TMP-SMX in microbiological eradication rates 4. However, fluoroquinolones should be reserved for more serious infections due to concerns about resistance and side effects 2.

Important Clinical Considerations

• Diagnosis: Can be made with high probability based on focused history of lower urinary tract symptoms (dysuria, frequency, urgency) and absence of vaginal discharge 2, 3

• Urine Testing:

  • Urine analysis provides minimal diagnostic benefit in patients with typical symptoms
  • Urine culture should be obtained in:
    • Suspected pyelonephritis
    • Symptoms that don't resolve within 72 hours
    • Symptoms that recur within 4 weeks after treatment
    • Women presenting with atypical symptoms
    • Pregnant women 2

• Treatment Duration:

  • Standard short courses are effective for uncomplicated cystitis
  • Extended treatment (7-14 days) recommended for patients with renal impairment 2

• Monitoring:

  • No routine post-treatment urinalysis or cultures needed if symptoms resolve 2
  • If symptoms don't improve within 72 hours, reevaluate with urine culture 2

Common Pitfalls to Avoid

• Avoid amoxicillin or ampicillin for empirical treatment due to poor efficacy and high worldwide resistance rates 2

• Avoid treating asymptomatic bacteriuria in non-pregnant women as it promotes antimicrobial resistance without clinical benefit 2

• Avoid fluoroquinolones as first-line therapy despite high efficacy to preserve their effectiveness for more serious infections 1, 2

• Avoid nitrofurantoin in patients with significant renal impairment (CrCl <30 mL/min), pregnant women in their third trimester, or patients with G6PD deficiency 2

• Consider local resistance patterns when selecting TMP-SMX, as resistance now approaches 18-22% in some regions of the US 2