How should I treat an uncomplicated cystitis in a patient with estimated glomerular filtration rate ≥60 mL/min who is not in the first trimester of pregnancy, and what alternatives are recommended if nitrofurantoin is contraindicated or the infection is complicated?

Treatment of Uncomplicated Cystitis with eGFR ≥60 mL/min

For uncomplicated cystitis in patients with eGFR ≥60 mL/min who are not in the first trimester of pregnancy, prescribe nitrofurantoin 100 mg orally twice daily for 5 days as first-line therapy. 1, 2

First-Line Treatment: Nitrofurantoin

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves clinical cure in 88-93% and bacteriological cure in 81-92% of cases. 2
• This regimen is superior to single-dose fosfomycin (70% vs 58% clinical resolution at 28 days, P=0.004) and provides better outcomes than trimethoprim-based regimens when eGFR is normal. 3, 4
• The 5-day duration is optimal; extending beyond 5-7 days provides no additional benefit and increases adverse event risk. 2

Alternative First-Line Options (When Nitrofurantoin Cannot Be Used)

If nitrofurantoin is contraindicated, choose alternatives based on this hierarchy:

Option 1: Fosfomycin

• Fosfomycin trometamol 3 g as a single oral dose 1, 5
• Clinical resolution rate is 58% at 28 days (modestly lower than nitrofurantoin but acceptable). 3
• Mix with water before ingesting; never take in dry form. 5
• Particularly useful when eGFR is 30-60 mL/min, where it outperforms nitrofurantoin (16.0% vs 23.3% failure rate). 4

Option 2: Trimethoprim-Sulfamethoxazole

• TMP-SMX 160/800 mg twice daily for 3 days 1, 6
• Use ONLY if:
  • Local E. coli resistance is documented <20% 1, 2
  • Patient has not received this agent in the preceding 3 months 2
• Contraindicated in the last trimester of pregnancy. 1
• Not recommended in first trimester of pregnancy. 1

Option 3: Pivmecillinam (where available)

• Pivmecillinam 400 mg three times daily for 3-5 days 1

Option 4: Cephalosporins (second-line)

• Cefadroxil 500 mg twice daily for 3 days or comparable cephalosporin 1
• Use only if local E. coli resistance <20% 1
• Beta-lactams demonstrate inferior efficacy compared to nitrofurantoin and should be reserved for when first-line agents are unsuitable. 2

Critical Contraindications to Nitrofurantoin

Do not prescribe nitrofurantoin if ANY of the following are present:

• Suspected pyelonephritis (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting) – nitrofurantoin does not achieve adequate renal tissue concentrations. 1, 2
• eGFR <30 mL/min – contraindicated due to reduced efficacy and increased risk of peripheral neuropathy. 2, 7
• eGFR 30-60 mL/min – use with extreme caution; fosfomycin is preferred in this range. 4
• Suspected prostatitis in men – nitrofurantoin does not penetrate prostatic tissue. 2

When to Suspect Complicated UTI (Requiring Different Management)

Switch to fluoroquinolone or parenteral therapy if:

• Fever, flank pain, or systemic symptoms suggest upper tract involvement 1, 2
• Structural/functional urinary tract abnormalities present 2
• Obstruction, foreign body, or incomplete voiding 7
• Immunosuppression or history of multidrug-resistant organisms 7
• Symptoms persist after 48-72 hours of appropriate therapy 7

Agents to Avoid for Uncomplicated Cystitis

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for pyelonephritis due to FDA warnings (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance rates (~24%). 2
• Amoxicillin or ampicillin alone should never be used empirically due to high global resistance. 2
• Gentamicin requires parenteral administration and carries nephrotoxicity/ototoxicity risk in elderly patients. 2

Follow-Up and Monitoring

• Routine post-treatment urine cultures are NOT indicated for asymptomatic patients. 1, 2
• Obtain urine culture with susceptibility testing only if:
  • Symptoms do not resolve by end of treatment 1
  • Symptoms recur within 2-4 weeks 1
  • Atypical presentation 1
• If retreatment is needed, assume resistance to the original agent and use a 7-day regimen of a different antibiotic. 1

Common Pitfalls to Avoid

• Do not use nitrofurantoin for "borderline" upper tract symptoms – any flank pain or low-grade fever warrants alternative therapy. 2
• Always verify renal function before prescribing – efficacy drops markedly when eGFR falls below 60 mL/min. 4
• Do not prescribe TMP-SMX empirically without knowing local resistance rates – treatment failure is unacceptably high when resistance exceeds 20%. 2
• Do not treat asymptomatic bacteriuria in non-pregnant patients or those not undergoing urological procedures. 1, 2

Adverse Effects

• Most common side effects of nitrofurantoin are nausea and headache (5.6-34% adverse event rate). 2
• Serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003%, respectively). 2
• Systemic inflammatory response syndrome secondary to nitrofurantoin has been reported in isolated cases. 8