What is the best treatment approach for a patient with recurrent urinary tract infections (UTIs) caused by Escherichia coli (E. coli) and presenting with leukocytosis?

Management of Recurrent UTI with E. coli and Leukocytosis

For a patient with recurrent E. coli UTI and leukocytosis, obtain urine culture with sensitivities before initiating treatment, then start empiric therapy with nitrofurantoin 100 mg twice daily for 5-7 days while awaiting culture results, and implement non-antimicrobial prevention strategies to break the recurrence cycle. 1, 2

Immediate Diagnostic Steps

• Obtain urine culture with antimicrobial susceptibility testing before starting antibiotics to guide therapy and document the specific organism causing this episode 1, 2
• Document whether this represents reinfection (>2 weeks after previous treatment or different organism) versus relapse (<2 weeks after treatment with same organism), as this distinction fundamentally changes management 1, 2
• If this is a relapse UTI (same organism within 2 weeks), reclassify as complicated UTI and consider imaging to identify structural abnormalities such as calculi, foreign bodies, or diverticula that cause bacterial persistence 1, 2

The presence of leukocytosis suggests systemic inflammatory response and warrants careful assessment to exclude pyelonephritis or early urosepsis, particularly in patients with risk factors for complicated infection 1, 3

First-Line Empiric Antibiotic Treatment

Nitrofurantoin is the preferred first-line agent with the following advantages:

• Dosing: 100 mg twice daily for 5-7 days maximum 1, 2
• Maintains remarkably low resistance rates even with repeated use (only 20.2% persistent resistance at 3 months versus 83.8% for fluoroquinolones) 2
• Effective against E. coli, which causes approximately 75% of recurrent UTIs 1
• Minimizes collateral damage to protective microbiota 2

Alternative first-line options if nitrofurantoin is contraindicated:

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 5-7 days, but only if local resistance patterns are favorable (<20% resistance) 1, 4, 5
• Fosfomycin 3 grams as a single dose for convenience and excellent compliance 1, 2

Critical Treatment Duration Principle

Treat acute episodes for 5-7 days maximum—no longer 1, 2

• Longer courses paradoxically increase recurrences by disrupting protective microbiota 2
• Avoid the temptation to use "greater potency" antibiotics or extended durations, as this approach worsens outcomes 2

What NOT to Do: Common Pitfalls

Avoid fluoroquinolones (ciprofloxacin, levofloxacin) as empiric therapy for the following reasons:

• Extremely high persistent resistance rates (83.8%) in recurrent E. coli UTI 2
• Should be reserved only for situations where first-line agents cannot be used and local fluoroquinolone resistance is <10% 2, 6
• Increased risk of serious adverse effects including tendon rupture, particularly in elderly patients 6

Do not treat asymptomatic bacteriuria between symptomatic episodes:

• This practice increases antimicrobial resistance without improving outcomes 1, 2
• Increases risk of subsequent symptomatic infections 2

Do not use broad-spectrum antibiotics when narrower options are available, as this accelerates resistance development 1, 2

Long-Term Prevention Strategy

Once the acute episode is treated, implement a stepwise prevention approach to break the recurrence cycle:

Non-Antimicrobial Measures (Try First) 1, 2

• Increase fluid intake to dilute urine and reduce bacterial concentration 1
• Practice urge-initiated voiding and post-coital voiding to reduce bacterial colonization 1, 2
• Avoid spermicide-containing contraceptives, which increase UTI risk 1
• For postmenopausal women: prescribe vaginal estrogen (≥850 µg weekly), which has strong evidence for prevention 1, 7
• Consider methenamine hippurate 1 gram twice daily for women without urinary tract abnormalities 1, 7

Antimicrobial Prophylaxis (If Non-Antimicrobial Measures Fail)

For patients with ≥3 UTIs per year or ≥2 UTIs in 6 months who fail non-antimicrobial interventions:

• Continuous prophylaxis: Nitrofurantoin 50-100 mg daily at bedtime for 6-12 months 1, 2, 7
• Post-coital prophylaxis: Single dose of nitrofurantoin or trimethoprim-sulfamethoxazole after intercourse if infections are temporally related to sexual activity 1, 3
• Patient-initiated (self-start) therapy: Provide prescription for short-course antibiotics (5-7 days) to start at first symptom onset for reliable patients 1, 2

The choice between these strategies depends on infection pattern: continuous prophylaxis for infections unrelated to sexual activity, post-coital for coitus-related infections, and self-start for sporadic unpredictable episodes 2, 3

When to Consider Imaging

Imaging is NOT routinely indicated for typical recurrent UTI in women without risk factors 1

DO obtain imaging (CT urography or ultrasound) if:

• Relapse UTI (same organism within 2 weeks of treatment completion) 1, 2
• Symptoms fail to resolve or recur within 2 weeks despite appropriate therapy 1
• Presence of risk factors: gross hematuria after infection resolution, urea-splitting bacteria, prior urinary calculi, symptoms of pneumaturia or fecaluria, or repeated pyelonephritis 1
• Suspected structural abnormalities causing bacterial persistence 1, 2

Adjusting Therapy Based on Culture Results

Once culture and sensitivity results return:

• If organism is resistant to empiric therapy but patient is improving clinically, complete the course 1
• If organism is resistant and patient is not improving, switch to a sensitive agent and complete 7-14 days total 1, 2
• For relapse UTIs with resistant organisms, consider parenteral antibiotics or infectious disease consultation 2
• Document organism and sensitivities to guide future prophylaxis selection 2, 3

Special Consideration: Distinguishing UTI from Other Conditions

Be aware that in patients with chronic pelvic pain syndromes, UTI symptoms may represent disease flares rather than true bacteriuria—only 9.4% of such patients with UTI symptoms have positive cultures 8. However, in the presence of documented leukocytosis and prior culture-proven E. coli infections, true bacterial infection is more likely 8, 9