Do I continue empiric Macrobid (nitrofurantoin) for a urinary tract infection (UTI) in a symptomatic patient with a negative urinalysis?

Should You Continue Empiric Macrobid for UTI with Negative Urinalysis but Symptomatic Patient?

Stop the nitrofurantoin and reassess for alternative diagnoses, as a negative urinalysis has excellent negative predictive value and effectively rules out UTI in most patients. 1

The Diagnostic Dilemma

A negative urinalysis (specifically negative for both nitrite AND leukocyte esterase) has excellent negative predictive value for UTI and should prompt you to stop antibiotics and look elsewhere for the cause of symptoms. 1

Key Diagnostic Principles:

• Urinalysis has high negative predictive value: When both nitrite and leukocyte esterase are negative, UTI is effectively ruled out in patients with functioning bone marrow 1

• Symptoms alone are insufficient: The presence of dysuria, frequency, or urgency without objective findings (pyuria or bacteriuria) does not justify continued antibiotic therapy 1

• Urine culture is essential: You should obtain urine culture and sensitivity with each symptomatic episode BEFORE initiating treatment in patients with recurrent symptoms 1

Clinical Algorithm for This Scenario:

Step 1: Verify the Urinalysis Results

• Confirm that BOTH nitrite AND leukocyte esterase are negative 1
• If either is positive, UTI remains possible and treatment may continue pending culture 1

Step 2: If Truly Negative UA

• Discontinue nitrofurantoin immediately 1
• Evaluate for alternative diagnoses causing urinary symptoms 1

Step 3: Consider Alternative Diagnoses

Look for these specific conditions that mimic UTI symptoms:

• Vaginitis or cervicitis: Perform pelvic examination for vaginal discharge, atrophy, or cervical motion tenderness 1
• Urethritis from STI: Consider testing for gonorrhea and chlamydia, especially in sexually active patients 1
• Interstitial cystitis/painful bladder syndrome: History of chronic pelvic pain, frequency without infection 1
• Pelvic organ prolapse: Physical examination findings of prolapse 1
• Overactive bladder: Urgency and frequency without dysuria or systemic symptoms 1

Step 4: If Symptoms Persist

• Obtain urine culture if not already done 1
• Consider referral to urology if recurrent symptoms without documented infection 1

Important Caveats and Pitfalls:

When Negative UA May Be Misleading:

Catheterized patients are the exception: In patients with indwelling catheters or ileal conduits, UA has very low specificity but maintains excellent negative predictive value, so a negative UA still rules out catheter-associated UTI 1

Timing matters: Ensure the urinalysis was performed on a properly collected midstream clean-catch specimen, not a random voided sample 1

The Danger of Continuing Unnecessary Antibiotics:

• Clostridium difficile risk: Unnecessary antibiotic use increases risk of C. difficile-associated diarrhea, which can range from mild diarrhea to fatal colitis 2

• Pulmonary toxicity: Nitrofurantoin carries risk of acute, subacute, or chronic pulmonary reactions that can be fatal, particularly with prolonged use 2

• Hepatotoxicity: Hepatic reactions including hepatitis and hepatic necrosis occur rarely but can be fatal 2

• Peripheral neuropathy: May become severe or irreversible, especially in patients with renal impairment, anemia, diabetes, or vitamin B deficiency 2

• Antimicrobial resistance: Continuing antibiotics without documented infection contributes to resistance patterns 1

Special Populations Requiring Different Approach:

Older/Frail Patients:

• These patients frequently present with atypical symptoms (confusion, functional decline, falls) 1
• However, the same principle applies: negative nitrite AND leukocyte esterase means no antibiotics for UTI 1
• Evaluate for other causes of delirium or functional decline 1

Pregnant Women:

• Different rules apply—always obtain urine culture in pregnant women with symptoms 1
• Asymptomatic bacteriuria requires treatment in pregnancy (unlike non-pregnant patients) 1

The Evidence Behind This Recommendation:

The 2024 JAMA Network Open guidelines explicitly state that UA has "excellent negative predictive value" and that "a negative UA can rule out CAUTI for patients with functioning bone marrow." 1 This principle extends to non-catheterized patients as well.

Furthermore, the European Association of Urology 2024 guidelines emphasize that diagnosis requires "typical symptoms in combination with detection of pathogens in the urine"—not symptoms alone. 1 The specificity of urine dipstick tests ranges from only 20-70% in elderly patients, but negative results reliably suggest absence of UTI. 1

The bottom line: A negative urinalysis should stop you in your tracks and redirect your diagnostic thinking away from UTI toward other causes of urinary symptoms.