Are all nitrite-negative urinary tract infections (UTIs) caused by gram-positive organisms?

Nitrite-Negative Urinary Tract Infections and Bacterial Etiology

Not all nitrite-negative urinary tract infections are caused by gram-positive organisms. While gram-positive organisms like Enterococcus typically do not produce nitrite, many gram-negative bacteria can cause nitrite-negative UTIs as well 1, 2.

Relationship Between Nitrite Status and Bacterial Type

Gram-Positive Organisms

• Gram-positive bacteria (particularly Enterococcus) do not reduce nitrate to nitrite 3
• Only 11% of gram-positive organisms yield a positive nitrite test 3
• Specifically, only 5.3% of samples with pure Enterococcus growth produce a positive nitrite test 3

Gram-Negative Organisms

• While gram-negative bacteria can produce nitrite, not all gram-negative UTIs will test positive:
  • Only 46% of gram-negative organisms yield a positive nitrite test 3
  • 95.6% of nitrite-negative UTIs are still caused by gram-negative bacteria 4
  • Enterobacterales (gram-negative) can cause nitrite-negative UTIs due to:
    • Lack of dietary nitrate
    • Dilution of urine
    • Exogenous interference (e.g., ascorbic acid)
    • Insufficient time for nitrate reduction 2

Clinical Implications

Diagnostic Value

• The nitrite test has limited sensitivity but good specificity:
  • Sensitivity: 53% (15-82%)
  • Specificity: 98% (90-100%) 5
• A negative nitrite test does not rule out gram-negative infection
• A positive nitrite test is highly predictive of the absence of pure enterococcal bacteriuria (predictive value 97.7%) 3

Treatment Decisions

• Physicians should not adjust antibiotic therapy for UTIs based on nitrite results alone 1, 6
• In a study comparing nitrite-positive and nitrite-negative UTIs:
  • 78% of nitrite-positive isolates were sensitive to TMP/SMX
  • 82% of nitrite-negative isolates were sensitive to TMP/SMX
  • No statistically significant difference in antibiotic sensitivity patterns 6

Pediatric Considerations

• Among nitrite-negative UTIs in children under 2 years:
  • 95.6% of uropathogens were gram-negative
  • Only 3.2% were Enterococcus 4
• The absence of nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children 4

Best Practice Recommendations

1. Always obtain urine culture for definitive identification of the causative organism and antimicrobial susceptibilities 7, 5
2. Do not rely solely on nitrite status to predict the bacterial etiology of UTI
3. Consider the combination of symptoms, pyuria, and bacteriuria rather than nitrite status alone when determining treatment 5
4. For empiric treatment of uncomplicated UTIs, standard first-line options remain appropriate regardless of nitrite status:
   • Trimethoprim-sulfamethoxazole
   • Nitrofurantoin
   • Cephalexin 5

Common Pitfalls to Avoid

• Assuming nitrite-negative UTIs are exclusively caused by gram-positive organisms
• Modifying empiric antibiotic therapy based solely on nitrite status
• Relying on dipstick tests alone without confirming with urine culture
• Overlooking the possibility of gram-negative bacteria in nitrite-negative samples

Remember that urine culture remains the gold standard for diagnosing UTI and identifying the causative organism, regardless of nitrite test results 2.