What first‑line oral antibiotic regimen is recommended for a 19‑year‑old patient with an uncomplicated nitrite‑positive urinary tract infection, assuming no drug allergies, normal renal function, and not pregnant?

First-Line Antibiotic Regimen for Nitrite-Positive Uncomplicated UTI in a 19-Year-Old

Prescribe trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg orally twice daily for 3 days if local E. coli resistance is <20% and the patient has not received TMP-SMX in the past 3 months; otherwise, use nitrofurantoin 100 mg orally twice daily for 5 days or fosfomycin 3 g as a single oral dose. 1

Diagnostic Significance of Nitrite-Positive Result

• A positive nitrite test has 95% specificity for urinary tract infection, making it highly reliable for confirming bacterial infection when present. 2, 3
• Nitrite positivity indicates gram-negative bacteria (primarily E. coli, which causes 75-95% of uncomplicated cystitis) because these organisms convert urinary nitrate to nitrite. 1, 2
• The positive predictive value of nitrite alone is 96%, meaning empirical antibiotic therapy is justified without awaiting culture results in this symptomatic patient. 2

First-Line Antibiotic Selection Algorithm

Step 1: Assess Local TMP-SMX Resistance

• If local E. coli resistance to TMP-SMX is <20% AND the patient has not used TMP-SMX in the past 3 months → prescribe TMP-SMX 160/800 mg orally twice daily for 3 days. 1
• TMP-SMX achieves 93% clinical cure and 94% microbiological eradication when the organism is susceptible, making it highly effective. 1

Step 2: If TMP-SMX Is Unsuitable

• Nitrofurantoin 100 mg orally twice daily for 5 days is the preferred alternative, achieving 93% clinical cure and 88% microbiological eradication with worldwide resistance rates <1%. 1
• Fosfomycin 3 g as a single oral dose provides 91% clinical cure with the convenience of single-dose administration and only 2.6% resistance in initial infections. 1

Why These Three Agents Are First-Line

• All three regimens (TMP-SMX, nitrofurantoin, fosfomycin) are endorsed by the European Association of Urology, American Urological Association, and American College of Physicians as first-line therapy for uncomplicated cystitis in women. 1
• These agents cause minimal disruption to intestinal flora, reducing the risk of Clostridioides difficile infection and other collateral damage compared to fluoroquinolones or broad-spectrum agents. 1
• Resistance rates remain low for nitrofurantoin (<1%) and fosfomycin (2.6%), making them reliable empirical choices. 1

Agents to Avoid as First-Line

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for culture-proven resistant organisms or documented failure of first-line therapy because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits in uncomplicated UTI. 1
• Beta-lactams (amoxicillin-clavulanate, cephalosporins) achieve only 89% clinical cure and 82% microbiological eradication, which is significantly inferior to first-line agents, and should be used only when first-line options are contraindicated. 1
• Amoxicillin or ampicillin alone should never be used because worldwide E. coli resistance exceeds 55-67%. 1

When to Obtain Urine Culture

• Routine urine culture is NOT required for otherwise healthy women with typical lower urinary tract symptoms (dysuria, frequency, urgency) and no vaginal discharge. 1
• Obtain urine culture and susceptibility testing if:
  • Symptoms persist after completing the prescribed regimen 1
  • Symptoms recur within 2-4 weeks 1
  • Fever >38°C, flank pain, or costovertebral angle tenderness suggesting pyelonephritis 1
  • Atypical presentation or presence of vaginal discharge 1

Critical Pitfalls to Avoid

• Do not use nitrofurantoin if eGFR <30 mL/min/1.73 m² because adequate urinary concentrations cannot be achieved. 1
• Do not use fosfomycin for suspected pyelonephritis or upper-tract infection due to insufficient tissue penetration. 1
• Do not prescribe TMP-SMX without confirming local resistance is <20%; failure rates increase sharply above this threshold. 1
• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized women, as this promotes resistance without clinical benefit. 1

Management of Treatment Failure

• If symptoms persist after 2-3 days or recur within 2 weeks, obtain urine culture and susceptibility testing immediately and switch to a different antibiotic class for a 7-day course (not the original short regimen). 1
• Assume the original pathogen is resistant to the previously used agent when retreating. 1