Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests

Area of Science:

• Infectious Diseases
• Clinical Microbiology
• Epidemiology

Background:

• Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) presents a significant diagnostic challenge, with over 50% of cases remaining without a clear etiology.
• The advent of polymerase chain reaction (PCR) and arboviral serologies has enhanced diagnostic capabilities for meningitis.
• Large-scale epidemiological studies evaluating the clinical utility of these advanced diagnostic methods are scarce.

Purpose of the Study:

• To prospectively evaluate the diagnostic yield and utilization of PCR and arboviral serologies in patients with meningitis and negative CSF-GS.
• To compare diagnostic outcomes between an early era (limited PCR availability) and a modern era (widespread PCR use).

Main Methods:

• A prospective observational study was conducted in New Orleans (early era, 1999-2008) and Houston (modern era, 2008-2013).
• 323 patients with meningitis and negative CSF-GS were enrolled and followed for 4 weeks.
• Data on all investigations, including PCR and serology, were systematically recorded.

Main Results:

• Polymerase chain reaction (PCR) demonstrated the highest diagnostic yield (24.2%), yet was under-utilized (ordered in 39.6% of cases).
• Arboviral serology yielded 15% of diagnoses and was ordered in 31% of patients.
• The overall rate of undiagnosed meningitis decreased from 72.1% in the early era to 53.4% in the modern era, primarily due to increased identification of viral pathogens (8.3% to 26.3%).

Conclusions:

• The implementation of PCR and arboviral serologies has significantly improved the diagnostic yield for meningitis cases with negative CSF-GS.
• Despite their effectiveness, both PCR and arboviral serologies are under-utilized in routine clinical practice, highlighting a gap between diagnostic potential and application.