Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era.

CONTEXT Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results because distinguishing bacterial meningitis from aseptic meningitis is often difficult. OBJECTIVE To develop and validate a simple multivariable 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 meningitis. 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 bacteria, CSF protein > or =80 mg/dL, peripheral absolute neutrophil count > or =10 000 cells/mm3, seizure before or at time of presentation, and CSF absolute neutrophil count > or =1000 cells/mm3. A Bacterial Meningitis Score (BMS) was developed 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 negative predictive value of a score of 0 for bacterial meningitis was 100% (95% confidence interval: 97%-100%). A BMS > or =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 > or =2) risk of bacterial meningitis. Outpatient management may be considered for children in the low-risk group.

[1]  A. Wilkinson,et al.  Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn. , 1993, Archives of disease in childhood.

[2]  S. Berliner,et al.  Cerebrospinal fluid leukocyte aggregation in meningitis. , 1997, The Pediatric infectious disease journal.

[3]  Hj Norussis,et al.  SPSS for Windows , 1993 .

[4]  P. Domenico,et al.  Bacterial or viral meningitis? Measuring lactate in CSF can help you know quickly. , 1990, Postgraduate medicine.

[5]  C Bohuon,et al.  Measurement of procalcitonin levels in children with bacterial or viral meningitis. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  F. Oski,et al.  Oski's pediatrics : principles and practice , 1999 .

[7]  J. Bertrand,et al.  High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  M. Lipsitch.  Interpreting results from trials of pneumococcal conjugate vaccines: a statistical test for detecting vaccine-induced increases in carriage of nonvaccine serotypes. , 2000, American journal of epidemiology.

[9]  S. Kaplan,et al.  Three-Year Multicenter Surveillance of Pneumococcal Meningitis in Children: Clinical Characteristics, and Outcome Related to Penicillin Susceptibility and Dexamethasone Use , 1998, Pediatrics.

[10]  W. Hacke,et al.  Serum procalcitonin levels in bacterial and abacterial meningitis , 2000, Critical care medicine.

[11]  J. Pachón,et al.  Cerebrospinal fluid tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, and interleukin‐8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients , 2000 .

[12]  S. Lockhart,et al.  Efficacy of a pneumococcal conjugate vaccine against acute otitis media. , 2001, The New England journal of medicine.

[13]  R. C. Baker,et al.  The predictive value of cerebrospinal fluid differential cytology in meningitis. , 1989, The Pediatric infectious disease journal.

[14]  National, state and urban area vaccination coverage levels among children aged 19-35 months--United States, July 1994-June 1995. , 1996, MMWR. Morbidity and mortality weekly report.

[15]  C. Hadjichristodoulou,et al.  Epidemiology of invasive childhood pneumococcal infections in Greece , 2000, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[16]  L. Mccawley,et al.  Cytokine elevations in infants with bacterial and aseptic meningitis. , 1995, The Journal of pediatrics.

[17]  B. Lowe,et al.  Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa , 2001, The Lancet.

[18]  R. Malley,et al.  Cerebrospinal fluid pleocytosis and prognosis in invasive meningococcal disease in children. , 1998, The Pediatric infectious disease journal.

[19]  J. Bradley,et al.  Safety and efficacy of once daily ceftriaxone for the treatment of bacterial meningitis. , 1986, Pediatric infectious disease.

[20]  J. Bradley,et al.  Outpatient therapy of serious pediatric infections with ceftriaxone. , 1988, The Pediatric infectious disease journal.

[21]  G. Rijkers,et al.  Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  E. Lewis,et al.  Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children , 2000, The Pediatric infectious disease journal.

[23]  C. Marchant,et al.  Acute phase reactants and risk of bacterial meningitis among febrile infants and children. , 1991, Annals of emergency medicine.

[24]  W. Bonadio.  The cerebrospinal fluid: physiologic aspects and alterations associated with bacterial meningitis , 1992, The Pediatric infectious disease journal.

[25]  M. Lipsitch.  Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae. , 1999, Emerging infectious diseases.

[26]  O. Gratzl,et al.  Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  M. McIntosh.  Dexamethasone therapy for children with bacterial meningitis , 1995 .

[28]  I. Stiell,et al.  Methodologic standards for the development of clinical decision rules in emergency medicine. , 1999, Annals of emergency medicine.

[29]  M. Mufson,et al.  A 20-year epidemiological study of pneumococcal meningitis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

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

[31]  A. Laupacis,et al.  Clinical prediction rules. A review and suggested modifications of methodological standards. , 1997, JAMA.

[32]  L. Anderson,et al.  Temporal and geographic patterns of isolates of nonpolio enterovirus in the United States, 1970-1983. , 1986, The Journal of infectious diseases.

[33]  S B Freedman,et al.  Predictors of bacterial meningitis in the era after Haemophilus influenzae. , 2001, Archives of pediatrics & adolescent medicine.

[34]  K. Oizumi,et al.  RETRACTED ARTICLE: Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis , 1998, Journal of Neurology.

[35]  W. Bonadio,et al.  Distinguishing Cerebrospinal Fluid Abnormalities in Children with Bacterial Meningitis and Traumatic Lumbar Puncture , 1990 .

[36]  J. Hicks,et al.  Cerebrospinal fluid lactic acid levels in meningitis. , 1977, The Journal of pediatrics.

[37]  J. Pettifor,et al.  Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children. , 2000, The Pediatric infectious disease journal.

[38]  A. Schuchat,et al.  Bacterial Meningitis in the United States in 1995 , 1997 .

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

[40]  D. Musher,et al.  Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis , 1998, Journal of Clinical Microbiology.

[41]  A. Leach.  Multidrug-resistant Streptococcus pneumoniae: An opportunity to further understand pneumococcal ecology and to better predict intervention outcomes. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[42]  J. Deeks,et al.  Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom. , 2000, JAMA.

[43]  L. Hansson,et al.  Serum C-reactive protein in the differential diagnosis of acute meningitis. , 1993, Scandinavian journal of infectious diseases.

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