What are the recommended dosing regimens of nitrofurantoin for uncomplicated cystitis in adults and children, and what are its contraindications and alternative treatments?

Nitrofurantoin Dosing for Uncomplicated Urinary Tract Infections

For uncomplicated cystitis in adults, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days, which achieves 70-93% clinical cure rates and is the preferred first-line agent due to minimal resistance patterns despite 60+ years of use. 1, 2

Adult Dosing Regimens

Standard Dosing for Uncomplicated Cystitis

• Nitrofurantoin monohydrate/macrocrystals: 100 mg orally twice daily for 5 days is the IDSA/ESCMID-recommended regimen for uncomplicated lower urinary tract infections in women. 1, 3
• The 5-day duration is optimal—extending beyond 5-7 days provides no additional efficacy and increases adverse event risk. 1
• Clinical cure rates range from 70-93% and microbiological cure rates from 74-92%. 1, 2

Alternative Formulation

• Nitrofurantoin macrocrystals: 50-100 mg orally four times daily for 5 days is an acceptable alternative per European guidelines. 1
• For VRE (vancomycin-resistant enterococci) uncomplicated UTIs specifically: 100 mg orally every 6 hours (four times daily). 4, 1

Pediatric Dosing

• Children ≥12 years: 100 mg orally twice daily for 7 days. 1
• Children <12 years: 5-7 mg/kg/day divided into 4 doses, maximum 100 mg/dose, for 7 days or at least 3 days after obtaining sterile urine. 1

Critical Contraindications

Absolute Contraindications

• Suspected or confirmed pyelonephritis (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting)—nitrofurantoin does not achieve adequate renal tissue concentrations and will fail. 1, 3
• Creatinine clearance <30 mL/min—contraindicated due to reduced efficacy and increased risk of peripheral neuropathy. 1, 5
• Last trimester of pregnancy (final 3 months). 6
• Perinephric abscess. 1

Clinical Pitfall to Avoid

• Do not use nitrofurantoin for "borderline" upper tract symptoms—any flank pain, low-grade fever, or systemic symptoms requires a fluoroquinolone (ciprofloxacin 500 mg twice daily for 5-7 days) or cephalosporin instead. 1

Renal Function Considerations

• CrCl 30-60 mL/min: Nitrofurantoin can be used with caution—one study showed 69% eradication rate in this range, with only 2 of 26 failures attributable to renal insufficiency itself. 5
• CrCl <30 mL/min: Avoid completely—efficacy drops markedly and peripheral neuropathy risk increases substantially. 1, 5
• The American Geriatrics Society specifically recommends avoiding nitrofurantoin in older adults with CrCl <30 mL/min. 1

When Nitrofurantoin Cannot Be Used: Alternative First-Line Options

For Uncomplicated Cystitis

• Fosfomycin trometamol 3 g orally as a single dose—though clinical cure (58%) and microbiological cure (63%) are modestly lower than nitrofurantoin (70% and 74% respectively). 1, 2
• Trimethoprim-sulfamethoxazole 160/800 mg orally twice daily for 3 days—ONLY if local E. coli resistance is <20% AND the patient has not received it in the preceding 3 months. 1, 3

For Suspected Pyelonephritis

• Ciprofloxacin 500 mg orally twice daily for 5-7 days for mild-to-moderate cases, provided local resistance data support its use. 1
• Ceftriaxone or cefotaxime (parenteral third-generation cephalosporins) for severe cases. 1

Comparative Efficacy: Nitrofurantoin vs. Fosfomycin

A 2018 JAMA randomized trial (n=513) directly compared these agents and found nitrofurantoin superior: 2

• Clinical resolution at 28 days: 70% (nitrofurantoin) vs. 58% (fosfomycin), absolute difference 12% (95% CI 4-21%, P=0.004). 2
• Microbiologic resolution: 74% vs. 63%, absolute difference 11% (95% CI 1-20%, P=0.04). 2
• This is the highest-quality head-to-head comparison and establishes nitrofurantoin as the more effective first-line agent. 2

Antibiotics to Avoid for Uncomplicated Cystitis

Fluoroquinolones (Ciprofloxacin, Levofloxacin)

• Should be reserved for pyelonephritis or complicated UTIs only—not for simple cystitis. 1, 3
• FDA warns of serious adverse effects: tendon rupture, peripheral neuropathy, CNS toxicity, aortic dissection. 1
• Community resistance rates now approach 24%, limiting empiric utility. 1
• WHO classifies ciprofloxacin as "Watch" category vs. nitrofurantoin's "Access" category, reflecting stewardship priorities. 1

Beta-Lactams (Cephalosporins, Amoxicillin-Clavulanate)

• Demonstrate inferior efficacy compared to nitrofurantoin for uncomplicated cystitis. 1
• Should be used only when first-line agents are unsuitable. 1, 3
• Amoxicillin or ampicillin alone should never be used empirically due to globally high resistance. 1

Aminoglycosides (Gentamicin)

• Require parenteral administration and are reserved for severe/hospitalized infections. 1
• Carry significant nephrotoxicity and ototoxicity risk in elderly patients. 1

Adverse Effects and Safety Profile

Common Side Effects

• Nausea and headache are most frequent, occurring in 5.6-34% of patients. 1
• Gastrointestinal complaints (nausea 3%, diarrhea 1%) are generally mild. 2

Rare but Serious Toxicities

• Pulmonary reactions: 0.001% incidence. 1
• Hepatic toxicity: 0.0003% incidence. 1
• Peripheral neuropathy: primarily with long-term use or renal insufficiency. 6
• Systemic inflammatory response syndrome: isolated case reports exist. 7

Clinical Decision Algorithm

Step 1: Confirm diagnosis of uncomplicated lower UTI

• Symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort. 1
• No fever >38°C, flank pain, nausea/vomiting, or costovertebral angle tenderness. 1
• Patient is non-pregnant, pre-menopausal, and has no urological abnormalities. 1

Step 2: Verify renal function

• Check creatinine clearance—if <30 mL/min, nitrofurantoin is contraindicated. 1, 5

Step 3: Prescribe nitrofurantoin

• 100 mg orally twice daily for 5 days. 1
• Ensure adequate hydration during treatment to prevent crystal formation. 1

Step 4: Follow-up only if symptomatic

• Routine post-treatment urine cultures are not indicated for asymptomatic patients. 1, 3
• If symptoms persist after therapy or recur within 2 weeks, obtain urine culture with susceptibility testing and consider retreatment with a 7-day regimen using a different agent. 1, 3

Special Clinical Scenarios

Concurrent Fluconazole Use

• Nitrofurantoin has no clinically significant drug-drug interactions with azole antifungals and remains the optimal choice. 1

Recurrent UTIs

• Nitrofurantoin is recommended for prophylaxis due to lower resistance development. 1
• Obtain urine culture before treatment to guide antibiotic selection. 1

Asymptomatic Bacteriuria

• Do not treat with antibiotics in non-pregnant patients or those not undergoing urological procedures. 1

Resistance Patterns and Stewardship

• Nitrofurantoin retains 95-98% susceptibility against E. coli despite more than 60 years of clinical use. 1
• This exceptional resistance profile makes it a cornerstone of antimicrobial stewardship for uncomplicated UTIs. 1, 6
• WHO classifies nitrofurantoin as an "Access" antibiotic, reflecting its favorable resistance profile and suitability for first-line empiric therapy. 1