Development and Validation of a Multivariable Predictive Model to Distinguish Bacterial From Aseptic Meningitis in Children in the Post-Haemophilus influenzae Era Lise E. Nigrovic, MD*; Nathan Kuppermann, MD, MPH§; and Richard Malley, MD*‡ ABSTRACT. Context. Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results be- cause distinguishing bacterial meningitis from aseptic meningitis is often difficult. Objective. To develop and validate a simple multiva- riable model to distinguish bacterial meningitis from aseptic meningitis in children using objective parameters available at the time of patient presentation. Design. Retrospective cohort study of all children with meningitis admitted to 1 urban children’s hospital from July 1992 through June 2000, randomly divided into derivation (66%) and validation sets (34%). Patients. Six hundred ninety-six previously healthy children aged 29 days to 19 years, of whom 125 (18%) had bacterial meningitis and 571 (82%) had aseptic meningi- tis. Intervention. Multivariable logistic regression and recursive partitioning analyses identified the following predictors of bacterial meningitis from the derivation set: Gram stain of cerebrospinal fluid (CSF) showing bacte- ria, CSF protein >80 mg/dL, peripheral absolute neutro- phil count >10 000 cells/mm 3 , seizure before or at time of presentation, and CSF absolute neutrophil count >1000 cells/mm 3 . A Bacterial Meningitis Score (BMS) was de- veloped on the derivation set by attributing 2 points for a positive Gram stain and 1 point for each of the other variables. Main Outcome Measure. The accuracy of the BMS when applied to the validation set. Results. A BMS of 0 accurately identified patients with aseptic meningitis without misclassifying any child with bacterial meningitis in the validation set. The neg- ative predictive value of a score of 0 for bacterial menin- gitis was 100% (95% confidence interval: 97%–100%). A BMS >2 predicted bacterial meningitis with a sensitivity of 87% (95% confidence interval: 72%–96%). Conclusions. The BMS accurately identifies children at low (BMS  0) or high (BMS >2) risk of bacterial meningitis. Outpatient management may be considered for children in the low-risk group. Pediatrics 2002;110: 712–719; prediction model, bacterial meningitis, aseptic meningitis. ABBREVIATIONS. CSF, cerebrospinal fluid; WBC, white blood cell count; Hib, Haemophilus influenzae type b; ANC, absolute neutrophil count; RBC, red blood cells; ROC, receiver operating characteristic; BMS, Bacterial Meningitis Score; NPV, negative pre- dictive value; CI, confidence interval; PPV, positive predictive value. B acterial meningitis remains an important cause of morbidity and mortality in children despite the advent of highly effective bacterial conju- gate vaccines. In the United States each year, there are close to 6000 new cases of bacterial meningitis, of which approximately half occur in children younger than 18 years of age. 1 Streptococcus pneumoniae and Neisseria meningitidis are the major bacterial patho- gens in children beyond the immediate neonatal pe- riod 1 and have associated overall mortality rates of 6% to 12% 2–4 and 3% to 5%, 1,5 respectively. Despite antimicrobial therapy, up to 25% of survivors of bacterial meningitis have significant sequelae, such as neurologic deficits or hearing loss. 6 Because discrimination between bacterial menin- gitis and aseptic meningitis at the time of presenta- tion is often difficult, children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital to receive broad-spectrum antibiotics pend- ing bacterial culture results. Previously, investigators have evaluated means to distinguish bacterial from aseptic meningitis before the results of blood and/or CSF cultures are available. When evaluated on pa- tients not previously treated with antibiotics, the CSF Gram stain has been reported to have a sensitivity between 60% and 92%. 7,8 Other rapidly available parameters, such as the peripheral white blood cell count (WBC) and the CSF WBC with differential, have wide zones of overlap in patients with bacterial and aseptic meningitis. 9 –14 Measurements of CSF leukocyte aggregation, CSF lactate, and serum pro- calcitonin lack either sensitivity or specificity and are not routinely available. 15–22 The serum concentration of C-reactive protein has been evaluated as well, but has limited value as it may be low early in bacterial disease or elevated in patients with viral infec- tions. 23,24 Endogenous inflammatory mediators such as CSF tumor necrosis factor-, interleukin-1, or interleukin-6 have good predictive power but are not routinely available in the clinical setting. 25,26 Two multivariable models have previously been developed to distinguish bacterial versus aseptic meningitis. The first study—which was derived from From the *Department of Medicine and ‡Divisions of Infectious Diseases and Emergency Medicine, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, and the §Department of Internal Medicine, Division of Emergency Medicine and the Department of Pediatrics, Univer- sity of California, Davis, School of Medicine, Davis, California. Received for publication Feb 19, 2002; accepted May 20, 2002. Reprint requests to (R.M.) Divisions of Infectious Diseases and Emergency Medicine, Children’s Hospital, 300 Longwood Ave, Boston MA 02115. E-mail: richard.malley@tch.harvard.edu PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- emy of Pediatrics. 712 PEDIATRICS Vol. 110 No. 4 October 2002 by on June 7, 2005 www.pediatrics.org Downloaded from