Mayo Clinic Proceedings Home

Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome



      To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain.

      Patients and Methods

      We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less.


      Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001.


      Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation.

      Abbreviations and Acronyms:

      ACO (adverse clinical outcome), CMV (cytomegalovirus), CSF (cerebrospinal fluid), ED (emergency department), MRI (magnetic resonance imaging), VZV (varicella zoster virus)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Tunkel A.R.
        • Hartman B.J.
        • Kaplan S.L.
        • et al.
        Practice guidelines for the management of bacterial meningitis.
        Clin Infect Dis. 2004; 39: 1267-1284
        • Elmore J.G.
        • Horwitz R.I.
        • Quagliarello V.J.
        Acute meningitis with a negative Gram's stain: clinical and management outcomes in 171 episodes.
        Am J Med. 1996; 100: 78-84
        • Lepow M.L.
        • Carver D.H.
        • Wright Jr, H.T.
        • Woods W.A.
        • Robbins F.C.
        A clinical, epidemiologic and laboratory investigation of aseptic meningitis during the four-year period, 1955-1958: I.
        N Engl J Med. 1962; 266: 1181-1187
        • Hasbun R.
        The acute aseptic meningitis syndrome.
        Curr Infect Dis Rep. 2000; 2: 345-351
        • Ray P.
        • Badarou-Acossi G.
        • Viallon A.
        • et al.
        Accuracy of the cerebrospinal fluid results to differentiate bacterial from non bacterial meningitis, in case of negative gram-stained smear.
        Am J Emerg Med. 2007; 25: 179-184
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Plum F.
        • Levy D.
        Predicting prognosis in coma: can one improve medical decisions?.
        Am J Med. 1978; 65: 224-226
        • van de Beek D.
        • de Gans J.
        • Spanjaard L.
        • Weisfelt M.
        • Reitsma J.B.
        • Vermeulen M.
        Clinical features and prognostic factors in adults with bacterial meningitis.
        N Engl J Med. 2004; 351: 1849-1859
        • Concato J.
        • Feinstein A.R.
        • Holford T.R.
        The risk of determining risk with multivariable models.
        Ann Intern Med. 1993; 118: 201-210
        • Braitman L.E.
        • Davidoff F.
        Predicting clinical states in individual patients.
        Ann Intern Med. 1996; 125: 406-412
        • Groenwold R.H.
        • Donders A.R.
        • Roes K.C.
        • Harrell Jr, F.E.
        • Moons K.G.
        Dealing with missing outcome data in randomized trials and observational studies.
        Am J Epidemiol. 2012; 175: 210-217
        • Spanos A.
        • Harrell Jr, F.E.
        • Durack D.T.
        Differential diagnosis of acute meningitis: an analysis of the predictive value of initial observations.
        JAMA. 1989; 262: 2700-2707
        • Hoen B.
        • Viel J.F.
        • Paquot C.
        • Gérard A.
        • Canton P.
        Multivariate approach to differential diagnosis of acute meningitis.
        Eur J Clin Microbiol Infect Dis. 1995; 14: 267-274
        • Leblebicioğlu H.
        • Esen S.
        • Bedir A.
        • Günaydin M.
        • Saniç A.
        The validity of Spanos' and Hoen's models for differential diagnosis of meningitis.
        Eur J Clin Micriobiol Infect Dis. 1996; 15: 252-254
        • Baty V.
        • Viel J.F.
        • Schuhmacher H.
        • Jaeger F.
        • Canton P.
        • Hoen B.
        Prospective validation of a diagnosis model as an aid to therapeutic decision-making in acute meningitis.
        Eur J Clin Microbiol Infect Dis. 2000; 19: 422-426
        • Brivet F.G.
        • Ducuing S.
        • Jacobs F.
        • et al.
        Accuracy of clinical presentation for differentiating bacterial from viral meningitis in adults: a multivariate approach.
        Intensive Care Med. 2005; 31: 1654-1660
        • Hasbun R.
        • Abrahams J.
        • Jekel J.
        • Quagliarello V.J.
        Computed tomography of the head before lumbar puncture in adults with suspected meningitis.
        N Engl J Med. 2001; 345: 1727-1733

      Linked Article

      • Prognostic Risk Score for Pleocytosis With a Negative Gram Stain: Valid but of Limited Utility in Bacterial Meningitis Patients
        Mayo Clinic ProceedingsVol. 88Issue 4
        • Preview
          Meningitis with a negative cerebrospinal fluid (CSF) Gram stain has an extensive differential diagnosis including both benign and life-threatening etiologies. Reliable prognostic risk stratification at presentation could aid physicians in management decisions and patient counseling in the emergency department. In the December 2012 issue of Mayo Clinic Proceedings, Khoury et al1 reported on the derivation and validation of a risk score for an adverse clinical outcome in this patient group. Patients were classified as low risk if they had normal neurologic examination findings, had a CSF glucose level of 45 mg/dL or higher, and were 60 years old or younger.
        • Full-Text
        • PDF