What are the first-line oral antibiotics for an otherwise healthy adult with uncomplicated cystitis?

First-Line Oral Antibiotics for Uncomplicated Cystitis in Healthy Adults

Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the preferred first-line treatment for acute uncomplicated cystitis in otherwise healthy adults. 1

Primary Treatment Recommendation

Nitrofurantoin is the drug of choice because it demonstrates robust efficacy (clinical cure rates 88-93%, microbiologic cure rates 81-92%), spares more systemically active agents for other infections, and maintains minimal resistance patterns. 1, 2

• Nitrofurantoin achieves superior clinical resolution compared to fosfomycin (70% vs 58% at 28 days, P=0.004) and comparable microbiologic eradication (74% vs 63%, P=0.04). 3
• The 5-day duration is clearly recommended based on guideline consensus. 1, 2
• Critical contraindication: Do not use if eGFR <30 mL/min due to reduced efficacy and increased toxicity risk. 4

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

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• Dosing: 160/800 mg (one double-strength tablet) twice daily for 3 days. 1, 2
• Use only if local resistance rates are documented <20% AND the patient has not used TMP-SMX for UTI in the previous 3 months. 1, 2
• Efficacy drops dramatically against resistant organisms (41-54% cure rates vs 84-88% for susceptible strains). 2
• Avoid in patients with sulfa allergies. 4, 2

Fosfomycin Trometamol

• Dosing: 3 grams as a single oral dose. 1, 5
• Achieves clinical cure rates of 90-91% but lower microbiologic cure (78-80%). 1, 5
• Preferred alternative when nitrofurantoin is contraindicated, particularly in renal impairment (eGFR <30 mL/min) or when patient compliance with multi-day regimens is questionable. 4, 2
• FDA-approved specifically for uncomplicated cystitis in women caused by E. coli and Enterococcus faecalis. 5
• Important limitation: Slightly inferior efficacy compared to nitrofurantoin and should be avoided if early pyelonephritis is suspected. 1, 2

Pivmecillinam

• Dosing: 400 mg twice daily for 3 days. 1
• Geographic limitation: Only available in European countries, not in North America. 2, 6
• Lower efficacy than other first-line agents; avoid if early pyelonephritis suspected. 1

Second-Line Options (Reserve for When First-Line Agents Cannot Be Used)

Fluoroquinolones

• Dosing: Ciprofloxacin 250 mg twice daily or levofloxacin for 3 days. 1, 2
• Highly effective (95% clinical cure rates) but should be reserved as alternative agents due to collateral damage concerns and promotion of resistance. 1, 2, 6
• Resistance prevalence is high in many geographic areas. 1
• Reserve for more serious infections rather than simple cystitis. 2

Oral β-Lactams

• Options include cefdinir, cefaclor, cefpodoxime-proxetil, or cephalexin for 3-7 days. 1, 2
• Generally inferior efficacy and more adverse effects compared to first-line agents. 2, 6
• Use only when no other recommended agents are available. 1, 2

Agents to Avoid

Never use amoxicillin or ampicillin empirically due to poor efficacy and globally high resistance rates among uropathogens. 1, 2

Treatment Algorithm

1. Confirm diagnosis: Dysuria, frequency, urgency, or suprapubic tenderness WITHOUT fever, flank pain, or signs of pyelonephritis. 1

2. Assess renal function:

   • If eGFR >30 mL/min → Nitrofurantoin 100 mg twice daily for 5 days 1, 4
   • If eGFR <30 mL/min → Fosfomycin 3 g single dose 4

3. Check allergy history:

   • Sulfa allergy → Avoid TMP-SMX; use nitrofurantoin or fosfomycin 4, 2
   • Penicillin allergy → Nitrofurantoin or fosfomycin remain safe options 4, 2

4. Consider local resistance patterns:

   • If TMP-SMX resistance >20% in your community → Do not use TMP-SMX empirically 1, 2

5. Evaluate compliance factors:

   • If adherence to multi-day regimen is questionable → Consider fosfomycin single dose 4

Common Pitfalls to Avoid

• Do not extend nitrofurantoin beyond 7 days or use in patients with eGFR <30 mL/min, as this increases toxicity without improving outcomes. 4
• Do not use fluoroquinolones as first-line therapy despite high efficacy, as this promotes resistance to agents needed for serious infections. 2
• Do not prescribe TMP-SMX empirically without knowing local resistance rates or if the patient used it recently. 1, 2
• Do not assume fosfomycin has equivalent efficacy to nitrofurantoin—it has lower microbiologic cure rates and should not be used if pyelonephritis is suspected. 1, 3
• Obtain urine culture if symptoms do not resolve within 2-4 days or if the patient has risk factors for resistant organisms. 4, 7