What oral antibiotic is preferred for an uncomplicated adult urinary tract infection with urine culture positive for Aerococcus urinae and Escherichia coli, assuming normal renal function and no nitrofurantoin allergy?

Oral Antibiotic Selection for Polymicrobial UTI with Aerococcus urinae and E. coli

For an uncomplicated urinary tract infection with both Aerococcus urinae and E. coli, prescribe nitrofurantoin 100 mg orally twice daily for 5 days, as this agent achieves excellent coverage of both pathogens with 100% susceptibility for A. urinae and >95% susceptibility for E. coli, while maintaining minimal resistance and collateral damage. 1, 2, 3

Rationale for Nitrofurantoin as First-Line Choice

• Dual-pathogen coverage: Nitrofurantoin demonstrates 100% susceptibility against A. urinae in clinical isolates and maintains 95.6% susceptibility against E. coli uropathogens, making it uniquely suited for this polymicrobial infection. 2, 3

• Clinical efficacy for A. urinae: A prospective observational study of aerococcal UTI showed nitrofurantoin achieved 71% clinical cure and 76% microbiological cure in A. urinae cystitis, supporting its real-world effectiveness. 4

• Superior resistance profile: Nitrofurantoin maintains only 2.3% resistance rates in E. coli compared to 24% for fluoroquinolones and 29% for trimethoprim-sulfamethoxazole, preserving its long-term utility. 3, 5

• Guideline-endorsed first-line agent: The European Association of Urology, American Urological Association, and American College of Physicians all recommend nitrofurantoin as first-line therapy for uncomplicated cystitis in women. 1

Alternative First-Line Options (in descending order of preference)

Fosfomycin 3 g single oral dose

• When to use: Patient preference for single-dose convenience or when adherence to multi-day regimens is a concern. 1
• Coverage considerations: Fosfomycin achieves 91% clinical cure for E. coli UTI and is recommended for uncomplicated cystitis, though specific data for A. urinae are limited. 1
• Critical limitation: Do not use fosfomycin if upper-tract involvement (pyelonephritis) is suspected, as efficacy data are insufficient. 1

Ampicillin 500 mg orally every 8 hours for 5–7 days

• When to use: When nitrofurantoin and fosfomycin are contraindicated (e.g., eGFR <30 mL/min/1.73 m²). 6
• Coverage rationale: A. urinae demonstrates 100% susceptibility to ampicillin in clinical isolates, and ampicillin retains activity against many E. coli strains when susceptibility is confirmed. 2
• Important caveat: Ampicillin alone has high worldwide E. coli resistance rates (>55%), so this choice assumes susceptibility testing confirms activity or is used when other options are unavailable. 1

Agents to Avoid in This Clinical Scenario

Trimethoprim-sulfamethoxazole (TMP-SMX)

• Why avoid: Should only be used when local E. coli resistance is <20%, and no data support its efficacy against A. urinae. 1, 7
• Resistance concern: Many communities now exceed the 20% resistance threshold for E. coli, making empiric use inappropriate without susceptibility data. 7

Fluoroquinolones (ciprofloxacin, levofloxacin)

• Why avoid: A. urinae demonstrates 10.9% resistance to ciprofloxacin in clinical isolates, and fluoroquinolones should be reserved for pyelonephritis or culture-proven resistant organisms. 1, 2
• Collateral damage: Fluoroquinolones cause significant disruption to intestinal flora and promote multidrug-resistant organisms including C. difficile. 1

Amoxicillin or ampicillin monotherapy (without susceptibility data)

• Why avoid: E. coli resistance to amoxicillin/ampicillin exceeds 55–67% worldwide, making empiric use inappropriate despite excellent A. urinae coverage. 1

Renal Function Considerations

• eGFR ≥30 mL/min/1.73 m²: Nitrofurantoin, fosfomycin, and TMP-SMX are all acceptable options. 1
• eGFR <30 mL/min/1.73 m²: Nitrofurantoin is contraindicated because urinary concentrations become insufficient for bacterial eradication; switch to ampicillin (if susceptible) or fosfomycin. 1

When to Obtain Urine Culture and Adjust Therapy

• Obtain culture immediately if:

  • Symptoms persist after completing the prescribed 5-day course
  • Symptoms recur within 2 weeks after treatment completion
  • Fever >38°C, flank pain, or costovertebral angle tenderness develops (suggesting pyelonephritis)
  • Patient has atypical presentation or risk factors for resistant organisms 1

• Management of treatment failure: Switch to a different antibiotic class for a 7-day course (not the original short regimen) and assume the original pathogen is resistant to the first agent. 1

Critical Clinical Pitfalls to Avoid

• Do not use oral fosfomycin for suspected pyelonephritis because tissue penetration is inadequate and efficacy data are lacking for upper-tract infections. 1

• Do not treat asymptomatic bacteriuria in non-pregnant patients, as this promotes unnecessary antimicrobial use and resistance without clinical benefit. 1

• Do not prescribe nitrofurantoin when eGFR <30 mL/min/1.73 m² because effective urinary concentrations cannot be achieved. 1

• Verify the infection is truly uncomplicated (no fever, flank pain, pregnancy, male sex, catheter use, immunosuppression, or anatomic abnormalities) before using short-course oral therapy. 1