What is the recommended treatment for a patient with dysuria and small leukocytes, but a negative urine culture?

Management of Dysuria with Pyuria but Negative Urine Culture

Treat empirically with antibiotics based on symptoms, as negative urine cultures do not exclude urinary tract infection and symptomatic patients benefit from antimicrobial therapy.

Diagnostic Interpretation

The presence of dysuria with leukocytes (pyuria) but a negative culture represents a common clinical scenario that requires treatment despite the negative microbiology:

• Pyuria with symptoms indicates infection even when standard cultures are negative, as bacteriuria is more specific than pyuria for detecting UTI, but symptomatic patients with pyuria still respond to antibiotics 1
• A negative dipstick test for leucocytes and nitrites has a 92% negative predictive value for infection by standard microbiological definitions, but this does not predict response to antibiotic treatment 2
• Women with dysuria and frequency who received trimethoprim (despite negative dipstick) had resolution of dysuria in 3 days versus 5 days with placebo (p=0.002), with only 24% having ongoing dysuria at day 3 versus 74% in placebo group 2

Consider Alternative Diagnoses

Before treating as UTI, evaluate for:

• Sexually transmitted urethritis (Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae) - particularly in sexually active patients with dysuria but negative standard urine culture 3
• Perform urethral Gram stain looking for ≥5 polymorphonuclear leukocytes per oil immersion field, and obtain nucleic acid amplification testing for gonorrhea and chlamydia 3
• Non-gonococcal urethritis presents with dysuria and may have pyuria but negative routine cultures 3

Recommended Empiric Treatment

For presumed uncomplicated cystitis with dysuria and pyuria:

First-line options (choose based on local resistance patterns):

• Nitrofurantoin 50-100 mg four times daily for 5 days 3
• Fosfomycin trometamol 3g single dose (women only) 3
• Trimethoprim-sulfamethoxazole only if local resistance <20% 1

Key treatment principles:

• The number needed to treat is 4 for symptom resolution with empiric antibiotics despite negative dipstick 2
• Nitrofurantoin maintains excellent susceptibility with only 5.5% resistance among E. coli isolates 4
• Treatment duration is typically 5-7 days for uncomplicated cystitis 3, 5

When to Obtain Urine Culture

Urine culture is indicated in these specific situations despite initial negative result:

• Symptoms that do not resolve or recur within 4 weeks after treatment completion 3
• Suspected acute pyelonephritis or systemic symptoms 3
• Atypical presentation 3
• Males (to exclude prostatitis, which requires 14 days of treatment) 5

Follow-Up Strategy

• If symptoms persist after 3 days, reevaluate and obtain repeat urine culture with susceptibility testing 3
• Assume the organism is not susceptible to the initially used agent and retreat with a 7-day course of a different antibiotic 3
• For recurrent symptoms (≥3 UTIs per year or 2 in 6 months), prior cultures within 2 years have good predictive value (0.85 for nitrofurantoin, 0.78 for trimethoprim-sulfamethoxazole) for guiding therapy 4

Critical Pitfalls to Avoid

• Do not withhold treatment based solely on negative culture when symptoms are classic for UTI - this leads to prolonged symptoms without benefit 2
• Do not use ciprofloxacin empirically if local resistance >10% or if patient used fluoroquinolones in last 6 months 3
• Do not treat asymptomatic bacteriuria if discovered incidentally, as this does not improve outcomes and promotes resistance 3
• Do not miss STI-related urethritis in sexually active patients - obtain appropriate testing for chlamydia and gonorrhea 3