What antibiotic to start when urine labs show positive leukocyte esterase (LE) and nitrite, indicating a bacterial urinary tract infection (UTI)?

Antibiotic Selection for UTI with Positive Leukocyte Esterase and Nitrite

For urinary tract infections with positive leukocyte esterase and nitrite on urinalysis, trimethoprim-sulfamethoxazole (TMP-SMX) should be the first-line empiric antibiotic therapy, unless local resistance patterns exceed 20% or patient-specific risk factors for resistance are present. 1, 2

Diagnostic Significance of Positive LE and Nitrite

• Positive nitrite has excellent specificity (98%) but limited sensitivity (53%), meaning a positive result strongly suggests UTI 2
• Leukocyte esterase has better sensitivity (83%) but lower specificity (78%) compared to nitrites 2
• The combination of positive leukocyte esterase AND positive nitrite has a high positive predictive value for UTI, making empiric antibiotic therapy appropriate 2, 3
• This combination achieves 93% sensitivity for detecting UTIs, making it an excellent screening tool 2

First-Line Antibiotic Options

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• FDA-approved for urinary tract infections caused by susceptible strains of E. coli, Klebsiella, Enterobacter, Morganella morganii, and Proteus species 1
• Recommended as first-line therapy for uncomplicated UTIs when local resistance rates are <20% 4
• Typical dosing: 160/800 mg (one double-strength tablet) twice daily for 3 days for uncomplicated cystitis in women; 7-14 days for complicated UTIs 1

Alternative First-Line Options

• Amoxicillin-clavulanate: Effective against beta-lactamase-producing isolates of E. coli, Klebsiella species, and Enterobacter species in UTIs 5
• Cefuroxime: 250 mg twice daily for uncomplicated UTIs; 500 mg twice daily for 10-14 days for complicated UTIs 6
• Fluoroquinolones (e.g., ciprofloxacin): Should be reserved for more serious infections due to increasing resistance (16.4% in some studies) and potential adverse effects 7, 8

Risk Factors for TMP-SMX Resistance

Avoid TMP-SMX as first-line therapy if any of these risk factors are present:

• Recurrent UTIs (OR 2.27) 4
• Genitourinary abnormalities (OR 2.31) 4
• TMP-SMX use within previous 90 days (OR 8.77) 4
• Local resistance rates exceeding 20% 4

Treatment Algorithm

1. For uncomplicated UTIs with positive LE and nitrite:

   • First-line: TMP-SMX 160/800 mg BID for 3 days 1
   • If risk factors for TMP-SMX resistance: Use amoxicillin-clavulanate or cefuroxime 5, 6

2. For complicated UTIs (males, pregnancy, immunosuppression, diabetes, structural abnormalities):

   • Obtain urine culture before starting antibiotics 6
   • First-line: TMP-SMX 160/800 mg BID for 7-14 days (if no risk factors for resistance) 1
   • Alternative: Cefuroxime 500 mg BID for 10-14 days 6
   • Consider initial IV therapy with ceftriaxone before transitioning to oral therapy for severe cases 6

3. For pyelonephritis:

   • Cefuroxime 500 mg BID for 10-14 days 6
   • Consider initial IV therapy before transitioning to oral therapy 6

Clinical Pearls and Caveats

• Always consider local resistance patterns when selecting empiric antibiotic therapy 6, 4
• For complicated UTIs and pyelonephritis, obtain urine culture before initiating therapy to guide targeted treatment 6
• If symptoms persist after 72 hours of treatment, reevaluate diagnosis and consider imaging to rule out complications 6
• Consider follow-up urine culture after completion of therapy for complicated UTIs or pyelonephritis to ensure resolution 6
• The combination of leukocyte esterase and nitrite testing has similar diagnostic efficiency to sediment microscopy, making it a reliable screening tool 3