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Pediatric Bacterial Meningitis Workup

  • Author: Martha L Muller, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Aug 19, 2015
 

Approach Considerations

Bacterial meningitis is a medical emergency. A firm diagnosis is usually made when bacteria are isolated from the cerebrospinal fluid (CSF) and evidence of meningeal inflammation is demonstrated by increased pleocytosis, elevated protein level, and low glucose level in the CSF. Timely collection and processing of CSF and isolation of an organism allows optimization of choice of antimicrobial agent and duration of therapy. CSF chemistries and cytology vary, depending on the maturity and age of the newborn.[16]

A lumbar puncture (LP) may be contraindicated in some of the following conditions: unstable patients with hypotension or respiratory distress who may not be able to tolerate the procedure, brain abscess, brain tumors or other cause of raised intracranial pressure, and occasionally infection at the lumbar puncture site.

The Bacterial Meningitis Score, a clinical decision rule developed by Nigrovic et al,[17] has shown high accuracy and usability and continues to be evaluated with respect to its effectiveness as an aid to identify those children with CSF pleocytosis who are at low risk for bacterial meningitis.[2] The components of the score include the following:

  • Positive CSF Gram stain
  • CSF absolute neutrophil count of 1000/µL or higher
  • CSF protein level of 80 mg/dL or higher
  • Peripheral blood absolute neutrophil count of 10,000/µL or higher
  • History of seizure before or at the time of presentation

Specific hematologic, radiographic (eg, computed tomography [CT] and magnetic resonance imaging [MRI]), and other studies assist in diagnosis.

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Blood and Urine Studies

Blood studies that may be indicated include the following:

  • Complete blood count (CBC) with differential
  • Blood cultures
  • Coagulation studies
  • Serum glucose
  • Electrolytes

Measurement of the serum glucose level close to the time of CSF collection is helpful for interpreting CSF glucose levels and assessing the likelihood of meningitis.

Bacterial antigen studies can be performed on urine and serum and can be useful in cases of pretreated meningitis; however, a negative bacterial antigen study result does not rule out meningitis. The group B streptococcal (GBS) antigen test in urine is unreliable and should not be used to make a diagnosis of sepsis or meningitis.

Some data suggest that procalcitonin may be a useful biomarker for distinguishing bacterial meningitis from aseptic meningitis. Its use may enhance the sensitivity of the Bacterial Meningitis Score.[18, 19, 17] In a retrospective analysis of admitted patients with meningitis, Dubos et al found procalcitonin at a level of 0.5 ng/mL to have a sensitivity of 99% and a specificity of 83% for differentiating bacterial from aseptic meningitis.[18]

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Lumbar Puncture and CSF Analysis

Definitive diagnosis is based on examination of CSF obtained via lumbar puncture. Opening and closing pressures should be measured in the cooperative patient. Similarly, the color of the CSF (eg, turbid, clear, or bloody) should be recorded. If the CSF is not crystal clear, administer treatment immediately without waiting for the results of CSF tests.

In a traumatic lumbar puncture, where bleeding occurs and the CSF is contaminated with blood, interpretation becomes especially difficult. In this situation, it is better to initiate treatment before the results of the CSF culture are available. In very bloody lumbar punctures, a drop of the fluid on the sterile dressing usually will produce a double ring if CSF is present. Generally, when in doubt, proceed with treatment and attempt the lumbar puncture again later.

In particular, if the patient shows signs of pending herniation, consider treatment without performing a lumbar puncture. The puncture can be performed later, when intracranial pressure (ICP) has been controlled and the patient is clinically stable. CT or MRI is helpful in managing patients who require control of ICP and herniation.

CSF studies

Perform total and differential cell counts, chemistries (ie, glucose and protein), Gram stains, and cultures on all CSF specimens. In a setting of antibiotic pretreatment, rapid bacterial antigen testing may be considered. Note that patients with both fulminant disease and poor immune response may not show cytologic or chemical changes in CSF. In about 2-3% of bacterial meningitis cases, bacterial cultures may be positive even when the Gram stain is negative and the cell counts and glucose and protein levels are normal.

White blood cell (WBC) counts higher than 1000/µL are usually caused by bacterial infections. Counts of 500-1000/µL may be bacterial or viral and call for further evaluation. Lower counts are usually associated with viral infections.

The total WBC count cannot definitely distinguish between bacterial and other causes. At one time, it was generally believed that a predominance of polymorphonuclear leukocytes (PMNs) pointed to bacterial meningitis, but this has been an unreliable indicator; bacterial meningitis may also present with a lymphocytic predominance. Attempts to differentiate bacterial and aseptic meningitis on the basis of percentage and absolute number of premature neutrophils (ie, bands) have not yielded diagnostic results.[20]

The use of a corrected ratio of WBCs to red blood cells (RBCs)—that is, 1:500—or the percentage of neutrophils to “normalize” the cell count was shown to have limited utility in predicting which patients would have meningitis. The “corrected CSF” was shown to underestimate the true WBC count, causing clinicians to underdiagnose borderline meningitis cases. Formulas to adjust the WBC count have not increased the specificity or sensitivity of CSF analysis in traumatic lumbar punctures in neonates.[21]

The CSF protein concentration is usually elevated in bacterial meningitis (greater than 50 mg/dL), but it is also elevated by a traumatic lumbar puncture. The CSF glucose concentration is usually reduced in bacterial meningitis. A normal CSF glucose level should be higher than two thirds of the serum glucose level; a CSF level lower than 50% of the serum level is suggestive of bacterial meningitis. In patients with very early disease, however, CSF protein and glucose values may be within the reference range.

A Gram stain of cytocentrifuged CSF may reveal bacterial morphology. The CSF should be plated immediately onto a chocolate and blood agar media. Smears of petechial lesions may reveal microorganisms on Gram stain. Although Gram stain may aid in diagnosis, the diagnosis may be missed in up to 30-40% of cases of culture-proven disease. The sensitivity of a positive Gram stain is 67%.[22]

Examination of a buffy coat smear also may reveal intracellular microorganisms. The results of a retrospective cohort study found that WBC counts in the CSF of febrile infants without bacterial or enteroviral infection are lower than was previously reported.[23]

Even when CSF results are otherwise normal, the fluid should still be sent for culture. Both N meningitidis meningitis and S pneumoniae meningitis are known to give normal CSF results. In an evidence-based article, Ray et al found that meningitis may still exist in 10% of children who have normal CSF analysis.[24] Their recommendation is to treat any child with antibiotics if there is a risk of bacterial meningitis.

Several tests based on the principle of agglutination are available for the detection of bacterial antigens in body fluids. Bacterial antigen detection can be carried out in samples of CSF, blood, and urine. A negative result, however, does not rule out bacterial infection. Antigen detection tests are most helpful in patients with partially treated meningitis in whom bacteria may not grow from CSF but antigens persist in body fluids. Antigen detection in urine is particularly helpful in such circumstances because urine can be concentrated severalfold in the laboratory.

Several gram-negative bacteria and higher serotypes of S pneumoniae have capsular antigens that cross-react with H influenzae type b polyribophosphate. Capsular antigens of group B meningococcus cross-react with K1-containing Escherichia coli. Gram stains of CSF are more sensitive than these rapid diagnostic tests for the detection of N meningitidis.

Partially treated meningitis

Many children receive antibiotics before definitive diagnosis is made. As a rule, a few doses of oral antimicrobial agents, or even a single injection of an antibiotic, do not significantly alter CSF findings, including bacterial cultures, especially in patients with H influenzae type b (Hib) disease. Oral antibiotics have never convincingly been shown to render patients with bacterial meningitis CSF culture–negative.

CSF cultures may become sterile rapidly if the pathogen was a pneumococcus or meningococcus, though cellular changes, an increase in protein, and low glucose levels persist. In such cases, CSF, blood, and urine should be tested for bacterial antigens; however, the presence of a negative antigen result does not entirely rule out a bacterial source.

In cases where antibiotic administration leads to CSF sterilization, polymerase chain reaction (PCR) testing may have a role to play in identifying the pathogen. PCR testing is able to identify the pathogen quickly and accurately and does not require a large number of organisms; however, it does require further validation in this setting.

Nigrovic et al found that Gram stain results (WBC count and absolute neutrophil count) in CSF were not affected by pretreatment with antibiotics; however, the rates of positive CSF culture and blood culture were lower with antibiotic pretreatment.[25] After pretreatment with antibiotics for 12 hours or longer, the patients had higher CSF glucose levels and lower CSF protein levels.

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CT and MRI

CT and MRI may reveal ventriculomegaly and sulcal effacement (see the images below).

Acute bacterial meningitis. This axial nonenhanced Acute bacterial meningitis. This axial nonenhanced CT scan shows mild ventriculomegaly and sulcal effacement.
Acute bacterial meningitis. This axial T2-weighted Acute bacterial meningitis. This axial T2-weighted MRI shows only mild ventriculomegaly.
Acute bacterial meningitis. This contrast-enhanced Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).
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Contributor Information and Disclosures
Author

Martha L Muller, MD Associate Professor of Pediatrics, Division of Infectious Diseases, University of New Mexico School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert Allan Felter, MD, FAAP, CPE, FACPE Professor of Clinical Pediatrics, Department of Pediatrics, Georgetown University School of Medicine; Medical Director, Pediatric Emergency Medicine and Inpatient Services, Inova Loudoun Hospital

Robert Allan Felter, MD, FAAP, CPE, FACPE is a member of the following medical societies: American Academy of Pediatrics and American College of Physician Executives

Disclosure: Nothing to disclose

Jeffrey Hom, MD, MPH, FACEP, FAAP Assistant Professor, Department of Pediatrics/Emergency Services and Department of Emergency Medicine, New York University School of Medicine

Jeffrey Hom, MD, MPH, FACEP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

David Jaimovich, MD Chief Medical Officer, Joint Commission International and Joint Commission Resources

David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Garry Wilkes, MBBS, FACEM Director of Emergency Medicine, Calvary Hospital, Canberra, ACT; Adjunct Associate Professor, Edith Cowan University, Western Australia

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Grace M Young, MD Associate Professor, Department of Pediatrics, University of Maryland Medical Center

Grace M Young, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians

Disclosure: Nothing to disclose.

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Acute bacterial meningitis. This axial nonenhanced CT scan shows mild ventriculomegaly and sulcal effacement.
Acute bacterial meningitis. This axial T2-weighted MRI shows only mild ventriculomegaly.
Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).
Table 1. Antibiotic Dosages for Neonatal Bacterial Meningitis, Adjusted by Weight and Age
Antibiotic Route Dosage
Birth Weight < 2000 g, Age 0-7 Days Birth Weight >2000 g, Age 0-7 Days Birth Weight < 2000 g, Age >7 Days Birth Weight >2000 g, Age >7 Days
Penicillins
Ampicillin IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
Penicillin G IV 50,000 U/kg q12h 50,000 U/kg q8h 50,000 U/kg q8h 50,000 U/kg q6h
Oxacillin IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
Ticarcillin IV, IM 75 mg/kg q12h 75 mg/kg q8h 75 mg/kg q8h 75 mg/kg q6h
Cephalosporins
Cefotaxime IV, IM 50 m mg/kg g q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q6h
Ceftriaxone IV, IM 50 mg/kg qd 50 mg/kg qd 50 mg/kg qd 75 mg/kg qd
Ceftazidime IV, IM 50 mg/kg q12h 50 mg/kg q8h 50 mg/kg q8h 50 mg/kg q8h
Table 2. Antibiotics for Neonatal Bacterial Meningitis That Must Be Dosed According to Serum levels
Antibiotic Route Desired Serum level, µg/mL Dosage
Birth Weight < 2000 g, Age 0-7 Days* Birth Weight >2000 g, Age 0-7 Days* Birth Weight < 2000 g, Age >7 Days* Birth Weight >2000 g, Age >7 Days*
Aminoglycosides
Amikacin† IV, IM 20-30 (peak), < 10 (trough) 7.5 mg/kg q12h 10 mg/kg q12h 10 mg/kg q8h 10 mg/kg q8h
Gentamicin† IV, IM 5-10 (peak), < 2.5 (trough) 2.5 mg/kg q12h 2.5 mg/kg q12h 2.5 mg/kg q8h 2.5 mg/kg q8h
Tobramycin† IV, IM 5-10 (peak), < 2.5 (trough) 2.5 mg/kg q12h 2.5 mg/kg q12h 2.5 mg/kg q8h 2.5 mg/kg q8h
Glycopeptide
Vancomycin*† IV, IM 20-40 (peak), < 10 (trough) 15 mg/kg q12h 15 mg/kg q8h 15 mg/kg q8h 15 mg/kg q6h
*The dosage stated is the highest within the dosage range.



† Serum levels must be monitored when patient has kidney disease or is receiving other nephrotoxic drugs; adjust doses accordingly.



Table 3. Dosages and Dosing Intervals for Intravenous Antimicrobials in Infants and Children With Bacterial Meningitis
Antibiotic IV Dosage Maximum Daily Dose Dosing Interval
Ampicillin 400 mg/kg/day 6-12 g q6h
Vancomycin 60 mg/kg/day 2-4 g q6h
Penicillin G 400,000 U/kg/day 24 million U q6h
Cefotaxime 200-300 mg/kg/day 8-10 g q6h
Ceftriaxone 100 mg/kg/day 4 g q12h
Ceftazidime 150 mg/kg/day 6 g q8h
Cefepime* 150 mg/kg/day 2-4 g q8h
Imipenem† 60 mg/kg/day 2-4 g q6h
Meropenem 120 mg/kg/day 4-6 g q8h
Rifampin 20 mg/kg/day 600 mg q12h
*Experience with this agent in pediatric patients is minimal; it is not licensed for treatment of meningitis.



† Because of possible seizures, this agent must be used with caution in treating meningitis.



Table 4. Chemoprophylaxis for Bacterial Meningitis Caused by Haemophilus influenzae or Neisseria meningitidis
Causative Organism Drug Name Age of Contact Dosage
Haemophilus influenzae Rifampin Adults >600 mg PO qd for 4 days
  =1 month 20 mg/kg PO qd for 4 days; not to exceed 600 mg/dose
  < 1 month >10 mg/kg PO qd for 4 days
Neisseria meningitidis Rifampin Adults 600 mg PO q12h for 2 days
  >1 month 10 mg/kg PO q12h for 2 days; not to exceed 600 mg/dose
  =1 month >5 mg/kg PO q12h for 2 days
Ceftriaxone >15 years 250 mg IM once
  =15 years >125 mg IM once
Ciprofloxacin =18 years >500 mg PO once
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