What to do next in a 66-year-old patient with urinary tract infection (UTI) symptoms and a negative urinalysis (UA)?

Management of UTI Symptoms with Negative Urinalysis in a 66-Year-Old

Do not prescribe antibiotics for urinary tract infection when urinalysis shows negative nitrite AND negative leukocyte esterase—instead, evaluate for alternative causes and actively monitor for new or worsening symptoms. 1

Diagnostic Algorithm

Step 1: Verify the Clinical Presentation

The European Association of Urology guidelines specify that antibiotics should only be prescribed if the patient has recent-onset dysuria PLUS at least one of the following: 1, 2

• Urinary frequency, urgency, or new incontinence
• Systemic signs (fever >37.8°C orally, rigors, shaking chills, or clear-cut delirium)
• Costovertebral angle pain or tenderness of recent onset

If dysuria is isolated without these accompanying features, do not treat as UTI. 2

Step 2: Interpret the Negative Urinalysis

A negative urinalysis (negative nitrite AND negative leukocyte esterase) effectively rules out UTI in most cases, even when symptoms are present. 1, 3 However, there is an important caveat: in patients with high pretest probability based on classic symptoms (dysuria, frequency, urgency), a negative dipstick does not completely exclude UTI. 3

The absence of pyuria (≥10 WBCs/high-power field) has excellent negative predictive value for excluding urinary infection. 1, 4

Step 3: Pursue Alternative Diagnoses

When UTI symptoms are present but urinalysis is negative, systematically evaluate for: 2, 5

Genitourinary causes:

• Overactive bladder syndrome (most common cause of isolated frequency) 5
• Urethritis (consider sexually transmitted infections—obtain nucleic acid amplification testing for Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae) 1
• Vaginitis or atrophic vaginitis (particularly in postmenopausal women)
• Interstitial cystitis/bladder pain syndrome
• Urolithiasis

Medication-related causes: 5

• Diuretics
• Anticholinergics
• Alpha-blockers

Systemic causes:

• Diabetes mellitus (polyuria mimicking frequency)
• Hypercalcemia

Step 4: When to Obtain Urine Culture Despite Negative UA

Obtain urine culture if: 1, 3

• Urosepsis is suspected (high fever, shaking chills, hypotension)—obtain paired blood cultures as well
• Symptoms are severe and clinical suspicion remains very high despite negative screening tests
• Patient is immunocompromised or neutropenic (may have significant bacteriuria without pyuria) 1

Critical Pitfalls to Avoid

Do not treat asymptomatic bacteriuria. Approximately 40% of institutionalized elderly patients have asymptomatic bacteriuria, which causes neither morbidity nor increased mortality and should never be treated. 1, 2 Treating it leads to unnecessary antibiotic exposure, promotes resistance, and increases adverse drug effects without clinical benefit. 5

Do not rely on nonspecific symptoms alone. Symptoms such as altered mental status, functional decline, fatigue, falls, confusion, or malaise—without localizing urinary symptoms—do not warrant antibiotic treatment in elderly patients. 1, 5 These symptoms are frequently observed in older adults and are not necessarily associated with bacteriuria. 1

Do not assume positive dipstick equals infection. Urine dipstick tests have poor specificity (20-70%) in elderly patients, and pyuria is commonly found in the absence of infection, particularly in older adults with lower urinary tract symptoms such as incontinence. 5, 3

Active Monitoring Strategy

If you decide not to treat, implement structured follow-up: 1

• Monitor vital signs and hydration status
• Perform repeated physical assessments
• Reassess if new symptoms arise or existing symptoms worsen
• Specifically watch for development of systemic signs (fever, rigors, altered mental status, hypotension) that would indicate progression to complicated UTI or urosepsis

When Antibiotics Are Warranted

If the patient subsequently develops qualifying symptoms (dysuria plus frequency/urgency/systemic signs) or if urine culture returns positive with significant growth (≥10² CFU/mL in symptomatic patients), first-line treatment options include: 1, 2

• Fosfomycin 3g single dose
• Nitrofurantoin (most uropathogens retain good sensitivity) 3
• Pivmecillinam
• Trimethoprim-sulfamethoxazole (only if local resistance <20%) 3

Avoid fluoroquinolones if local resistance >10% or if the patient used them in the last 6 months, as elderly patients experience increased adverse effects. 1, 2