What is nitrofurantoin and how is it used to treat urinary tract infections?

Nitrofurantoin for Urinary Tract Infections

Nitrofurantoin is a first-line antibiotic for uncomplicated lower urinary tract infections that concentrates in the urinary tract and is effective against most common uropathogens while maintaining low resistance rates compared to other antibiotics. 1, 2

Mechanism and Properties

Nitrofurantoin is a synthetic nitrofuran derivative that:

• Functions as a prodrug requiring activation by bacterial nitroreductases
• Inhibits bacterial DNA, RNA, cell wall, and protein synthesis once activated 3
• Concentrates in the urine, achieving therapeutic levels in the urinary tract
• Has maintained good activity against common uropathogens like Escherichia coli, Staphylococcus saprophyticus, and Enterococcus species despite over 60 years of use 4
• Shows remarkably low resistance rates (approximately 2.3%) compared to fluoroquinolones (24%) and trimethoprim-sulfamethoxazole (29%) 5

Clinical Applications

First-line Treatment for Lower UTIs

Nitrofurantoin is recommended as a first-choice option for uncomplicated lower urinary tract infections by multiple guidelines:

• The Infectious Diseases Society of America (IDSA) and European Society for Microbiology and Infectious Diseases recommend it as a first-line therapy 1, 2
• The WHO Expert Committee includes it as one of the first-choice options for lower UTIs 1
• Standard dosing is 100 mg twice daily for 5 days 2

Advantages Over Other Antibiotics

• Maintains high susceptibility rates against E. coli (>95%) 5
• Lower risk of promoting antimicrobial resistance compared to fluoroquinolones 6
• Fluoroquinolones are now recommended to be reserved for more serious infections due to safety concerns and resistance issues 1, 2
• Trimethoprim-sulfamethoxazole has higher resistance rates (approximately 29%) 5

Contraindications and Precautions

• Absolutely contraindicated in patients with:

  • Renal impairment (GFR <30 ml/min) 2, 4
  • Last trimester of pregnancy 4
  • Infants under 3 months

• Use with caution in:

  • Elderly patients (higher risk of adverse effects) 6
  • Patients with G6PD deficiency
  • Patients with history of pulmonary disease

Potential Adverse Effects

• Pulmonary reactions: Range from mild dyspnea to noncardiogenic pulmonary edema, especially with long-term use 7

  • Symptoms include fever, dyspnea, chills, cough, and chest pain
  • Usually resolves with drug discontinuation

• Other adverse effects:

  • Gastrointestinal disturbances (nausea, vomiting)
  • Peripheral neuropathy (primarily with long-term use)
  • Hepatotoxicity (rare)
  • Brown discoloration of urine (harmless)

Clinical Pearls

• Nitrofurantoin is not effective for pyelonephritis or systemic infections as it does not achieve adequate tissue levels outside the urinary tract 1
• For recurrent UTIs, nitrofurantoin can be used for prophylaxis at lower doses (50-100 mg daily) 2
• Metabolites can potentiate nitrofurantoin's activity against non-growing bacteria, which may be relevant in certain UTI scenarios 3
• Despite being an older antibiotic, nitrofurantoin has gained renewed importance due to increasing resistance to other antibiotics 6, 5

Treatment Algorithm for UTIs

1. For uncomplicated lower UTIs in patients with normal renal function:

   • Nitrofurantoin 100 mg twice daily for 5 days
   • Alternative: Trimethoprim-sulfamethoxazole if local resistance <20%

2. For patients with renal impairment (GFR <30 ml/min):

   • Avoid nitrofurantoin
   • Consider amoxicillin-clavulanic acid or appropriate alternative based on susceptibility

3. For upper UTIs (pyelonephritis):

   • Nitrofurantoin is not appropriate
   • Use ciprofloxacin or ceftriaxone/cefotaxime based on severity 1

4. For recurrent UTIs:

   • Consider prophylactic nitrofurantoin 50-100 mg daily 2

By using nitrofurantoin appropriately for lower UTIs, clinicians can effectively treat infections while preserving broader-spectrum antibiotics for more serious conditions, thus supporting antimicrobial stewardship efforts.