What is the recommended work‑up and antibiotic regimen for hematuria associated with an uncomplicated urinary‑tract infection in an otherwise healthy adult?

Management of Hematuria Associated with Uncomplicated Urinary Tract Infection

First-Line Antibiotic Selection

Nitrofurantoin 100 mg orally twice daily for 5–7 days is the preferred first-line agent for uncomplicated cystitis with hematuria in otherwise healthy adults. This recommendation prioritizes low resistance rates (<5%), high urinary concentrations, and minimal disruption of intestinal flora compared with fluoroquinolones or broad-spectrum agents. 1

Alternative First-Line Options

• Fosfomycin trometamol 3 g as a single oral dose provides approximately 91% clinical cure with the convenience of single-dose administration, making it an excellent alternative when adherence is a concern or when nitrofurantoin is contraindicated. 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg orally twice daily for 3 days may be used only when local E. coli resistance is <20% and the patient has not received this agent in the preceding 3 months; many regions now exceed this threshold, requiring verification of local antibiogram data before empiric use. 2, 1

Reserve (Second-Line) Agents

• Fluoroquinolones (ciprofloxacin 250–500 mg twice daily or levofloxacin 250–750 mg once daily for 3 days) should be reserved exclusively for culture-proven resistant organisms or documented failure of first-line therapy because of serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity), rising global resistance (>10% in many regions), and substantial disruption of gut microbiota. 1

• Beta-lactam agents (amoxicillin-clavulanate, cefdinir, cefpodoxime for 3–7 days) achieve only 89% clinical cure and 82% microbiological eradication—significantly inferior to first-line options—and should be used only when first-line agents are contraindicated. 1

• Amoxicillin or ampicillin alone should never be used because worldwide E. coli resistance exceeds 55–67%. 1

Diagnostic Work-Up for Hematuria in the Setting of UTI

When Hematuria Does NOT Require Further Investigation

Microscopic or mild gross hematuria accompanying acute UTI symptoms does not require imaging or urologic referral when the patient is <35 years old, has no malignancy risk factors (smoking, occupational chemical exposure, chronic indwelling catheter), and the hematuria resolves after treatment. 3

When Hematuria DOES Require Further Investigation

• Advise patients to return for further evaluation if hematuria persists beyond 6 weeks after completing antibiotics; at that point, imaging (CT urography or renal ultrasound) and cystoscopy are indicated to exclude malignancy or urolithiasis. 3

• Gross hematuria in adults ≥35 years or in anyone with malignancy risk factors warrants prompt urologic referral, as the association with underlying malignancy is 30–40%. 3

• The presence of a positive urine culture does not decrease the likelihood of urologic malignancy; in one prospective study of 161 patients with hematuria and positive urine culture, 20% had a urologic malignancy diagnosed, with 12% presenting with metastatic disease. 4

Clinical Decision Algorithm

Step 1: Confirm Diagnosis of Uncomplicated UTI with Hematuria

• Both pyuria (≥10 WBC/HPF or positive leukocyte esterase) AND acute urinary symptoms (dysuria, frequency, urgency, fever >38.3°C, or gross hematuria) must be present before initiating antimicrobial therapy. 2, 3

• Obtain urine culture with susceptibility testing before starting antibiotics in patients with recurrent UTIs (≥2 episodes in 6 months or ≥3 in 12 months), treatment failure, atypical presentations, pregnancy, or suspected pyelonephritis. 3

• Routine urine culture is not required for otherwise healthy women presenting with typical uncomplicated cystitis symptoms and no risk factors for resistance. 3

Step 2: Assess for Complicated Infection

• Fever >38.3°C, costovertebral angle tenderness, nausea/vomiting, or inability to tolerate oral intake indicate possible pyelonephritis requiring 7–14 days of therapy and mandatory urine culture. 3

• Male sex, pregnancy, diabetes, immunosuppression, indwelling catheter, recent urologic instrumentation, or anatomical abnormalities convert the infection to complicated UTI, mandating culture and longer treatment (7–14 days). 3

Step 3: Initiate Empiric Therapy

• If local TMP-SMX resistance is <20% and no recent exposure: prescribe TMP-SMX 160/800 mg twice daily for 3 days. 1

• If TMP-SMX is unsuitable: choose nitrofurantoin 100 mg twice daily for 5–7 days (preferred) or fosfomycin 3 g single dose based on patient preference and renal function. 1

• Reserve fluoroquinolones for culture-proven resistance or when first-line agents are contraindicated. 1

Step 4: Reassess and Follow-Up

• Reassess clinical response within 48–72 hours; if symptoms persist or worsen, modify antibiotics based on culture results and consider imaging (ultrasound or CT) to rule out obstruction, stones, or abscess. 3

• If symptoms persist after 2–3 days or recur within 2 weeks, obtain urine culture and switch to a different antibiotic class for a 7-day course, assuming resistance to the initial agent. 1

• No routine follow-up culture is needed for uncomplicated cystitis that resolves clinically. 3

Step 5: Hematuria-Specific Follow-Up

• If hematuria resolves with UTI treatment and patient is <35 years with no risk factors: no further work-up needed. 3

• If hematuria persists >6 weeks after treatment: refer for urologic evaluation with CT urography and cystoscopy to exclude malignancy or urolithiasis. 3

• If patient is ≥35 years or has malignancy risk factors: arrange urologic evaluation after infection treatment regardless of hematuria resolution. 3

Critical Pitfalls to Avoid

• Do not delay urologic evaluation in patients with gross hematuria and positive urine culture, as 20% of such patients have urologic malignancy, with 12% presenting with metastatic disease. 4

• Do not treat asymptomatic bacteriuria (positive culture without symptoms); it occurs in 15–50% of older adults and provides no benefit while promoting resistance. 1, 3

• Do not prescribe nitrofurantoin courses shorter than 5 days; minimum effective duration is 5 days to avoid treatment failure. 1

• Do not assume hematuria is solely infection-related in patients ≥35 years or those with malignancy risk factors; arrange urologic evaluation after infection treatment. 3

• Do not use empiric fluoroquinolones as first-line therapy for uncomplicated cystitis due to serious adverse effects and rising resistance. 1

Special Considerations

• The presence of hematuria does not alter the selected antibiotic or duration of therapy for uncomplicated acute cystitis. 1

• In pregnant women, standard short-course treatment or single-dose fosfomycin is recommended for uncomplicated UTI with hematuria. 1

• Instruct patients to seek immediate care if they develop fever >38.3°C, flank pain, nausea/vomiting, or inability to tolerate oral intake, as these signs indicate possible pyelonephritis requiring urgent evaluation. 3