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

Abstract

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Keywords: Aseptic meningitis; Gram stain; epidemiology; meningitis; polymerase chain reaction; viral meningitis.

Fig. 1.

Investigations performed to establish diagnosis by period/location, on patients with meningitis and a negative Gram stain. P value was calculated using Fisher's exact test comparing the number of tests performed in each category between patients in Houston and New Orleans. Patients with more than one test were counted only once in each category. CSF BinaxNow (Alere, USA) is a rapid immunochromatographic CSF assay. * Serology for cytomegalovirus, Mycoplasma pneumonia, Bartonella, leptospirosis, Rocky Mountain spotted fever, Ehrlichia. † Serology on CSF and serum for West Nile virus and other arboviruses (St Louis encephalitis, western and eastern equine encephalitis, California encephalitis).