How should a male patient with leukocyturia be treated, both if symptomatic and if asymptomatic?

Treatment of Male Patients with Positive Leukocytes in Urine

In male patients with leukocyturia, treatment depends entirely on whether symptoms and bacteriuria are present: symptomatic men with bacteriuria require antibiotic therapy, while asymptomatic men with isolated leukocyturia (sterile pyuria) require diagnostic evaluation to identify the underlying cause but should not receive empiric antibiotics. 1

Symptomatic Patients with Leukocyturia

When Infection is Confirmed (Bacteriuria Present)

• Initiate empiric antibiotic therapy immediately based on local resistance patterns while awaiting culture results, as all UTIs in men are considered complicated and require thorough evaluation. 1

• Obtain urine culture to guide definitive antibiotic selection, particularly for recurrent or suspected complicated infections. 1

• Treatment duration should be at least 7 days for uncomplicated cystitis symptoms, though most male UTIs warrant longer courses given their complicated nature. 2

• For acute bacterial prostatitis, prescribe a 30-day course of appropriate antibiotics (typically fluoroquinolones or trimethoprim-sulfamethoxazole). 2

• For chronic bacterial prostatitis, consider 6-12 months of low-dose suppressive therapy, as cure rates are suboptimal and relapses are common. 2

Symptomatic Patients WITHOUT Bacteriuria (Sterile Pyuria)

• Complete a focused medical history assessing symptom duration, severity, associated symptoms (dysuria, frequency, urgency, nocturia), sexual activity, and previous episodes. 1

• Perform digital rectal examination to evaluate prostate size, consistency, and tenderness—distinguishing benign prostatic hyperplasia from prostatitis. 1

• Use the International Prostate Symptom Score (IPSS) to quantify severity: 0-7 mild, 8-19 moderate, 20-35 severe. 1

• Obtain a 3-day frequency-volume chart when nocturia or storage symptoms predominate to identify nocturnal polyuria versus reduced bladder capacity. 1

• Measure post-void residual (PVR) by bladder ultrasound; PVR >100-200 mL indicates significant obstruction requiring different management. 1

• Perform uroflowmetry if available; Qmax <10 mL/second indicates severe obstruction warranting immediate urologic referral. 1

Treatment Based on Findings:

For BPH-related symptoms (enlarged prostate on DRE):

• Start alpha-blocker monotherapy (tamsulosin 0.4 mg daily) as first-line therapy, providing symptom relief within 2-4 weeks. 3

• Add a 5-alpha reductase inhibitor (finasteride 5 mg daily or dutasteride 0.5 mg daily) if prostate volume >30 cc, PSA >1.5 ng/mL, or moderate-to-severe symptoms persist after 4 weeks of alpha-blocker therapy. 3

• Reassess at 2-4 weeks for alpha-blockers and 3-6 months for 5-alpha reductase inhibitors to evaluate treatment response. 3

For storage symptoms (frequency, urgency, nocturia) without obstruction:

• Implement behavioral modifications first: fluid management targeting ~1 liter urine output per 24 hours, reduce evening fluid intake, avoid bladder irritants (caffeine, alcohol, spicy foods), and increase physical activity. 1

• Consider antimuscarinic agents or beta-3 agonists (mirabegron) only after confirming PVR <150 mL, as these medications can precipitate retention in obstructed patients. 4

Asymptomatic Patients with Leukocyturia

Critical Distinction: Asymptomatic Bacteriuria vs. Sterile Pyuria

• Do NOT treat asymptomatic bacteriuria in adult men with antibiotics, as this leads to resistant organisms without clinical benefit—the exceptions are pregnant women and preschool children. 2

• High-quality research demonstrates that 50% of men with chronic prostatitis/chronic pelvic pain syndrome and 40% of completely asymptomatic control men have ≥5 WBCs per high-power field in expressed prostatic secretions, indicating leukocyturia alone has poor diagnostic specificity. 5

• Similarly, 32% of symptomatic patients versus 19% of asymptomatic controls had ≥5 WBCs per high-power field in post-prostatic massage urine, further confirming that isolated leukocyturia is common in healthy men. 5

Recommended Approach for Asymptomatic Leukocyturia:

• Repeat urinalysis to confirm persistent leukocyturia and rule out contamination, ensuring proper midstream clean-catch technique. 6

• Obtain urine culture to definitively exclude occult infection; if culture is negative, this represents sterile pyuria. 6

• When contamination is excluded and leukocyturia persists without significant bacteriuria, further diagnostic evaluation is mandatory. 6

Diagnostic Workup for Sterile Pyuria:

• Consider sexually transmitted infections (Chlamydia trachomatis, Neisseria gonorrhoeae) in sexually active men, particularly those <35 years, as these pathogens cause urethritis with leukocyturia but may not grow on standard urine culture. 1, 7

• Evaluate for tuberculosis with acid-fast bacilli smears and mycobacterial cultures in high-risk populations or those with constitutional symptoms. 2

• Screen for interstitial cystitis/bladder pain syndrome if storage symptoms develop later.

• Assess for nephrolithiasis with renal ultrasound or CT if flank pain or hematuria is present.

• Rule out malignancy (bladder cancer, renal cell carcinoma) with cystoscopy and upper-tract imaging in men >40 years with risk factors (smoking, occupational exposures) or concurrent hematuria. 1

Mandatory Immediate Urologic Referral Criteria

Refer to urology BEFORE initiating treatment if any of the following are present:

• Neurological disease affecting bladder function (multiple sclerosis, spinal cord injury, Parkinson's disease). 1

• Severe obstruction with Qmax <10 mL/second on uroflowmetry. 1

• Recurrent UTIs (≥2 episodes in 6 months or ≥3 in 12 months). 1

• Hematuria (microscopic or gross). 1

• Abnormal PSA exceeding age-adjusted reference ranges. 1

• Palpable bladder or PVR >200-300 mL suggesting urinary retention. 1

• DRE findings suspicious for prostate cancer (nodules, asymmetry, induration). 1

• Renal insufficiency potentially due to obstructive uropathy. 3

Common Pitfalls to Avoid

• Do not prescribe empiric antibiotics for asymptomatic leukocyturia without documented bacteriuria, as this promotes antimicrobial resistance without clinical benefit. 1, 2

• Do not initiate antimuscarinic agents without first measuring PVR, as men with elevated baseline residual volumes are at high risk for acute urinary retention. 4

• Do not add 5-alpha reductase inhibitors in men without prostatic enlargement (prostate volume <30 cc, PSA <1.5 ng/mL), as these medications are completely ineffective in this population and expose patients to unnecessary sexual side effects. 3

• Do not delay urologic referral in elderly patients with severe obstruction, as the risk of acute urinary retention increases dramatically with age (34.7 episodes per 1,000 patient-years in men aged 70+). 3

• Do not rely solely on leukocyte counts to diagnose infection, as the high prevalence of WBCs in asymptomatic men (40% with ≥5 WBCs/hpf) raises questions about the clinical usefulness of leukocyturia as a diagnostic tool. 5

Follow-Up Strategy

• Patients initiated on alpha-blocker therapy should be reassessed at 2-4 weeks using repeat IPSS to quantify improvement. 3

• Patients started on 5-alpha reductase inhibitors require evaluation at 3-6 months, as these medications have slower onset with maximal benefit requiring at least 6 months. 3

• Annual follow-up is recommended once symptoms are controlled to monitor for disease progression, treatment failure, or development of complications requiring intervention. 3