First-Line Antibiotics for Uncomplicated UTI
Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line treatment for uncomplicated urinary tract infections in women, based on the most recent guidelines from the Infectious Diseases Society of America (IDSA) and American Urological Association (AUA). 1, 2
Primary First-Line Options
The following agents are recommended as first-line therapy, listed in order of preference:
Nitrofurantoin 100 mg twice daily for 5 days - This is the preferred agent due to lower treatment failure rates compared to trimethoprim-sulfamethoxazole, minimal collateral damage to normal flora, and continued effectiveness against multi-drug resistant organisms 1, 2
Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days - Use ONLY if local E. coli resistance rates are below 20% 1, 2. Rising resistance rates have necessitated revising previous recommendations that made this the traditional first-line agent 3, 1
Fosfomycin trometamol 3 g single dose - Convenient single-dose option, though it may have slightly inferior efficacy compared to standard short-course regimens 1, 2
Critical Decision Points
When selecting empiric therapy, consider these factors:
Check local resistance patterns - If E. coli resistance to TMP-SMX exceeds 20% in your region, do not use it as first-line therapy 1, 2
Assess renal function - If creatinine clearance is <60 mL/min, avoid nitrofurantoin and consider TMP-SMX or amoxicillin-clavulanate instead 1
Rule out upper UTI - If the patient has fever, flank pain, or systemic symptoms suggesting pyelonephritis, nitrofurantoin is contraindicated as it does not achieve adequate tissue concentrations 1
Agents to Reserve or Avoid
Fluoroquinolones (ciprofloxacin, levofloxacin) - Should be reserved as alternative agents, NOT first-line, despite high efficacy 3, 1, 2. The FDA has issued warnings about serious adverse effects affecting tendons, muscles, joints, nerves, and the central nervous system 1. These agents cause significant collateral damage to normal flora and promote resistance 2
β-lactam agents (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) - Use only when first-line agents cannot be used, as they have inferior efficacy and more adverse effects 3, 1
Amoxicillin or ampicillin alone - Should NOT be used for empirical treatment due to poor efficacy and very high prevalence of antimicrobial resistance worldwide 3, 2
Diagnostic Approach
No urine culture needed before treatment in straightforward cases of acute uncomplicated cystitis in otherwise healthy women 1
Obtain urine culture and sensitivity in these situations: recurrent UTIs, treatment failure, symptoms persisting/recurring within 2-4 weeks, history of resistant organisms, or atypical presentation 2, 4
Self-diagnosis is sufficient - In women with typical symptoms (frequency, urgency, dysuria, nocturia, suprapubic pain) without vaginal discharge, clinical diagnosis is accurate enough to start treatment 4
Common Pitfalls to Avoid
Do not treat asymptomatic bacteriuria - Treatment does not improve outcomes and promotes antimicrobial resistance 1, 2
Do not use surveillance urine testing in asymptomatic patients with recurrent UTIs 1, 2
Do not be deterred by rare toxicity concerns - The risk of serious pulmonary toxicity with nitrofurantoin is 0.001% and hepatic toxicity is 0.0003%, which should not prevent its use for short-term treatment 1, 2
Special Populations
Men with uncomplicated UTI - Use trimethoprim, TMP-SMX, or nitrofurantoin for 7 days (longer duration than women), and always obtain urine culture to guide therapy 4
Recurrent UTIs - Obtain urinalysis, urine culture, and sensitivity with each symptomatic episode prior to initiating treatment 1. Consider patient-initiated self-start treatment while awaiting culture results in select patients 2
Resistant organisms - For vancomycin-resistant Enterococcus (VRE) causing uncomplicated UTIs, use nitrofurantoin 100 mg every 6 hours 1