Differentiating Acute Bacterial Meningitis From Acute Viral Meningitis Among Children With Cerebrospinal Fluid Pleocytosis: A Multivariable Regression Model

Background: Although accurate models for predicting acute bacterial meningitis exist, most have narrow application because of the specific variables selected for them. In this study, we estimate the accuracy of a simple new model with potentially broader applicability. Methods: On the basis of previous reports, we created a reduced multivariable logistic regression model for predicting bacterial meningitis that relies on age (years) (AGE), cerebrospinal fluid (CSF), total protein (TP) and total neutrophil count (TNC) alone. Data were from children ages 1 month–18 years diagnosed with acute enteroviral or bacterial meningitis whose initial CSF revealed >7 white blood cells/mm3. A fractional polynomial model was specified and validated internally by the bootstrap procedure. The area under the receiver operating characteristic curve (discrimination: criterion standard, >0.7), the Hosmer-Lemeshow deciles-of-risk statistic (calibration: criterion standard, P > 0.05) and sensitivity-specificity pairs at prespecified probability thresholds of the model were computed. Results: We identified 60 children with bacterial meningitis and 82 with enteroviral meningitis. At an area under the receiver operating characteristic curve of 0.97, our model represented by the equation: log odds of bacterial meningitis = 0.343 − 0.003 TNC − 34.802 TP0.5 + 21.991 TP − 0.345 AGE, was highly accurate when differentiating between bacterial and enteroviral meningitis. The model fit the data well (Hosmer-Lemeshow statistic; P =[r] 0.53). At probability cutoffs between 0.1 and 0.4, the model had sensitivity values between 98 and 92% and specificity values between 62 and 94%. Conclusions: Among children with CSF pleocytosis, a prediction model based exclusively on age, CSF total protein and CSF neutrophils differentiates accurately between acute bacterial and viral meningitis.

[1]  K. Nelson,et al.  Community-acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954-1976. , 1980, Reviews of infectious diseases.

[2]  J. Viel,et al.  Prospective Validation of a Diagnosis Model as an Aid to Therapeutic Decision-Making in Acute Meningitis , 2000, European Journal of Clinical Microbiology and Infectious Diseases.

[3]  S. Kaplan,et al.  Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group. , 1995, Pediatrics.

[4]  S. Kaplan,et al.  Dexamethasone Therapy for Children With Bacterial Meningitis , 1995, Pediatrics.

[5]  P. Royston,et al.  Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling. , 1994 .

[6]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[7]  Nathan Kuppermann,et al.  Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era. , 2002, Pediatrics.

[8]  G. Guyatt,et al.  Users' Guides to the Medical Literature: III. How to Use an Article About a Diagnostic Test: B. What Are the Results and Will They Help Me In Caring for My Patients? , 1994 .

[9]  J A Swets,et al.  Measuring the accuracy of diagnostic systems. , 1988, Science.

[10]  David W. Hosmer,et al.  Applied Logistic Regression , 1991 .

[11]  The validity of Spanos' and Hoen's models for differential diagnosis of meningitis , 1996, European Journal of Clinical Microbiology and Infectious Diseases.

[12]  O. Villavicencio,et al.  Acute aseptic meningitis syndrome. , 1963, Journal of the Philippine Medical Association.

[13]  Sunil J Rao,et al.  Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis , 2003 .

[14]  B. Hoen,et al.  Validation of a Diagnosis Model for Differentiating Bacterial from Viral Meningitis in Infants and Children under 3.5 Years of Age , 2000, European Journal of Clinical Microbiology and Infectious Diseases.

[15]  G. Guyatt,et al.  Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. , 1994, JAMA.

[16]  P. Rantakallio,et al.  Incidence and prognosis of central nervous system infections in a birth cohort of 12,000 children. , 1986, Scandinavian journal of infectious diseases.

[17]  J. Heitman Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases , 2000 .

[18]  F. Harrell,et al.  Differential diagnosis of acute meningitis. An analysis of the predictive value of initial observations. , 1989, JAMA.

[19]  J. Viel,et al.  Multivariate approach to differential diagnosis of acute meningitis , 1995, European Journal of Clinical Microbiology and Infectious Diseases.

[20]  K. Kelleher,et al.  Cerebrospinal fluid findings in aseptic versus bacterial meningitis. , 2000, Pediatrics.

[21]  A. Gean,et al.  The spinal tap: a new look at an old test. , 1986, Annals of internal medicine.