Can Adenosine Deaminase (ADA) levels be elevated in bacterial meningitis?

Adenosine Deaminase (ADA) in Bacterial Meningitis

Yes, adenosine deaminase (ADA) levels can be falsely elevated in bacterial meningitis, potentially leading to diagnostic confusion with tuberculous meningitis. While ADA is primarily used as a marker for tuberculous meningitis, multiple studies have documented its elevation in bacterial meningitis cases as well.

ADA Levels in Different Types of Meningitis

• ADA levels are significantly higher in tuberculous meningitis (mean 11.80 ± 2.50 IU/L) compared to bacterial meningitis (mean 8.52 ± 3.60 IU/L) and viral meningitis (mean 5.26 ± 1.90 IU/L) 1
• Bacterial meningitis can present with elevated ADA levels that may overlap with the lower range of values seen in tuberculous meningitis, creating diagnostic challenges 2
• Fulminant bacterial meningitis has been specifically identified as a cause of false-positive ADA elevation in cerebrospinal fluid 3

Diagnostic Value and Limitations

• ADA cannot reliably distinguish between bacterial meningitis and tuberculous meningitis when used as a standalone test 2
• When using ADA for diagnosis, values between 4-8 IU/L are insufficient to confirm or exclude tuberculous meningitis, as there is significant overlap with bacterial meningitis in this range 2
• CSF ADA values >8 IU/L have better specificity (>96%) for tuberculous meningitis but lower sensitivity (<59%), meaning bacterial meningitis can still occasionally present with these higher values 2

Improving Diagnostic Accuracy

• Combining CSF and serum ADA measurements improves diagnostic accuracy - using cutoffs of ≥10 IU/L for CSF and ≥15 IU/L for serum increases specificity from 92% to 97% for diagnosing tuberculous meningitis 1
• ADA should be interpreted alongside other CSF parameters rather than in isolation 4
• When differentiating partially treated bacterial meningitis from tuberculous meningitis, a cutoff ADA level of ≤5 IU/L has a sensitivity of 62.5% and specificity of 88.9% 5

CSF Parameters in Bacterial Meningitis

• The typical CSF picture in bacterial meningitis includes pleocytosis with predominantly polymorphonuclear leukocytes, low glucose concentration, low CSF-to-blood glucose ratio, and elevated protein levels 6
• CSF lactate is often elevated in bacterial meningitis and has better diagnostic accuracy than CSF white blood cell count in differentiating bacterial from other types of meningitis 6
• CSF lactate dehydrogenase (LDH) is significantly elevated in bacterial meningitis and may help differentiate it from other forms of meningitis 4

Clinical Approach to Diagnosis

• No single CSF test is fully reliable in distinguishing bacterial meningitis from other forms of meningitis, and results should be interpreted in the clinical context 6
• Multiple diagnostic algorithms have been developed to help differentiate between bacterial and viral meningitis, but none are 100% sensitive 7
• CSF culture remains the gold standard for diagnosis of bacterial meningitis, with positive results in 70-85% of patients who have not received prior antimicrobial therapy 7
• CSF Gram stain permits rapid identification of the causative bacterium in 60-90% of patients with community-acquired bacterial meningitis 7

Practical Considerations

• Prior antibiotic treatment may modify CSF findings, though CSF WBC count may not be greatly affected by antibiotics given before lumbar puncture 6
• If bacterial meningitis is suspected and lumbar puncture is delayed for any reason, empirical antibiotic therapy should be started immediately after blood cultures are obtained 6
• In immunocompromised patients, normal CSF parameters do not rule out meningitis, and a high index of suspicion should be maintained until cultures are final 6