Pediatric Bacterial Meningitis: An Update on Early Identification and Management

Table of Contents

 

Since bacterial meningitis can present with many signs and symptoms, differentiation of bacterial meningitis from viral meningitis and from other mimics can be difficult. If the presentation is not “classic” in nature, diagnostic and therapeutic delay can occur, frequently with devastating consequences. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients. You will learn:

The most common causative pathogens, based on patient age

Typical clinical findings that are consistent with bacterial meningitis and how they vary for patients in different age groups

Which physical examination findings indicate that a patient should undergo lumbar puncture

Inflammatory markers in the serum and cerebrospinal fluid, such as procalcitonin, can help detect serious bacterial illness

How clinical prediction scores, such as the bacterial meningitis score, can help distinguish between bacterial meningitis and viral meningitis

Which antibiotic are recommended, and when they should be started

The potential benefits of adjunct therapies, such as corticosteroids, and when they are indicated

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology and Pathophysiology
   1. Causative Pathogens and Mechanisms of Infection
6. Differential Diagnosis
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
      1. Neck Findings
      2. Skin Findings
      3. Findings That Indicate a Patient Should Undergo Lumbar Puncture
9. Diagnostic Studies
   1. Scoring Systems
   2. Serum Studies
      1. Procalcitonin
   3. Lumbar Puncture
      1. Cerebrospinal Fluid Analysis
   4. Imaging
10. Treatment and Complications
    1. Initial Approach
    2. Intravenous Fluids
    3. Antimicrobial Therapy
       1. Empiric Antimicrobial Therapy
       2. Antimicrobial Therapy for Patients Aged < 1 Month
       3. Antimicrobial Therapy for Patients Aged ≥ 1 Month
    4. Neurologic Complications
11. Special Circumstances
    1. Aseptic Meningitis
    2. Lyme Meningitis
    3. Tuberculous Meningitis
    4. Immunocompromised State
    5. Penetrating Trauma or Recent Neurosurgery
    6. Concurrent Urinary Tract Infection
12. Controversies and Cutting Edge
    1. Corticosteroids
13. Disposition
14. Summary
15. Risk Management Pitfalls in the Management of Pediatric Patients With Bacterial Meningitis
16. Time- And Cost-Effective Strategies
17. Case Conclusions
18. Clinical Pathway for the Management of Pediatric Patients With Suspected Bacterial Meningitis
19. Tables
    1. Table 1. Pathogens That Cause Bacterial Meningitis, Based on Patient Age
    2. Table 2. Bacterial Meningitis Score for Children
20. References

Abstract

The presentation of bacterial meningitis can overlap with viral meningitis and other conditions, and emergency clinicians must remain vigilant to avoid delaying treatment for a child with bacterial meningitis. Inflammatory markers, such as procalcitonin, in the serum and cerebrospinal fluid may help distinguish between bacterial meningitis and viral meningitis. Appropriate early antibiotic treatment and management for bacterial meningitis is critical for optimal outcomes. Although debated, corticosteroids should be considered in certain cases. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients.

Case Presentations

On a warm day in June, an unvaccinated 9-year-old girl is sent to your ED. Earlier that day, she was seen at her primary care physician’s office by a physician assistant who reported that the child had headache and fever intermittently for 3 to 4 days. The PA was concerned that she might have meningitis. The patient arrives, ambulatory and alert, complaining of a bitemporal headache. Her fever at home was 38.3°C (101°F). There has been no photophobia or rash, and there are no ill contacts. The child took acetaminophen 2 hours prior to arrival. On physical examination, the child is tired but not toxic-appearing. She had an episode of vomiting in triage. Her vital signs are: temperature, 38.7°C (101.6°F); heart rate, 142 beats/min; respiratory rate, 22 breaths/min; blood pressure, 119/77 mm Hg; and oxygen saturation, 95% on room air. Her pain score is 8/10. Her physical examination is notable for head and neck discomfort when moving from sitting to the supine position. Her neck has full range of motion and she is negative for Kernig sign and Brudzinski sign. The remainder of her examination is normal. The patient is given a 20 mL/kg normal saline bolus IV, 6 mg ondansetron IV, and 10 mg/kg ibuprofen orally. An hour later, her vital signs are: temperature, 37.2°C (99°F); heart rate, 126 beats/min; respiratory rate, 20 breaths/min; and blood pressure 111/67 mm Hg. Her pain score is now 4/10. Her peripheral white blood cell count is 16,000 with a left shift, and her chemistry is notable only for a glucose level of 146 mg/dL. Given the girl’s lack of frank meningismus and improvement with ibuprofen, is a lumbar puncture indicated? What are the most common causes of meningitis in this age group? Should antibiotics be given?

A 4-month-old boy presents with a history of cough, pallor, fever to 38.9°C (102°F), and decreased feeding on the morning of presentation. The infant drank 6 ounces about 4 hours before arrival, but would not feed at presentation. The boy’s parents state he did not vomit or have diarrhea. His past medical history is notable for cesarean delivery at 36 weeks' gestation. There was prolonged rupture of membranes and he was hospitalized for 3 days after delivery. The boy’s parents report no prior illnesses, and his immunizations are up-to-date. On physical examination, the boy’s vital signs are: temperature, 38.9°C (99.6°F); heart rate, 158 beats/min; respiratory rate, 50 breaths/min; and oxygen saturation, 98% on room air. The boy is arousable but sleepy and does not fix and follow. His fontanel is flat. His HEENT examination is notable for nasal congestion with mucus secretions. The boy’s cardiopulmonary and abdominal examinations are unremarkable. The boy’s capillary refill is < 2 seconds, but his muscle tone is decreased. He is fussy during the examination. Is this merely an upper respiratory infection or should meningitis be considered? What are common clinical features of meningitis in this age group? What further management is indicated? Which empiric antibiotics—if any—are indicated at this time?

Introduction

Bacterial meningitis in children is one of the most high-risk diagnostic and management challenges for the emergency clinician. Widespread implementation of vaccination strategies against pneumococcal, meningococcal, and Haemophilus influenzae type b diseases has led to a dramatic decline in the frequency of this condition over the past 3 decades.^1,2 In some ways, however, this has made the early identification of bacterial meningitis more difficult for the emergency clinician. The rare occurrence of the condition means that a high-volume pediatric emergency clinician may evaluate only 1 child with bacterial meningitis every 3 to 5 years. Since bacterial meningitis can present with many signs and symptoms, differentiation of bacterial meningitis from viral meningitis and from other mimics can be difficult. If the presentation is not “classic” in nature, diagnostic and therapeutic delay can occur, frequently with devastating consequences. Inflammatory markers in the serum and cerebrospinal fluid, such as procalcitonin, may help distinguish between bacterial meningitis and viral meningitis. Children with suspected bacterial meningitis should be treated early and aggressively. Adjunct therapies such as corticosteroids are still highly debated but may be indicated in select cases. Until better diagnostic tools and therapies are established, emergency clinicians must remain vigilant to avoid treatment delays for a child with bacterial meningitis.

This issue of Pediatric Emergency Medicine Practice reviews the classic clinical findings associated with bacterial meningitis, offers guidance for using studies and scoring systems to aid in the diagnosis of bacterial meningitis, and provides evidence-based recommendations for the management of patients with bacterial meningitis.

Critical Appraisal of the Literature

A literature search was performed in PubMed and the Cochrane Database of Systematic Reviews using the search terms: pediatric bacterial meningitis, viral meningitis, pediatric lumbar puncture, neonatal fever, antibiotics for pediatric meningitis, and pediatric meningitis diagnostic studies. A total of 98 articles published between 1992 and 2018 were reviewed.

The literature regarding bacterial meningitis management and therapy contains multiple multicenter trials and systematic reviews presenting strong evidence. More-recent articles, including several prospective cohort studies, have evaluated novel markers of bacterial meningitis.

Risk Management Pitfalls in the Management of Pediatric Patients With Bacterial Meningitis

2. “The patient has inflamed tympanic membranes. The fever and irritability are likely due to otitis media. It’s not meningitis.”

Many young children with bacterial meningitis can have concomitant inflammation in other areas on physical examination or diagnostic study. Otitis media and upper respiratory tract infections are common enough conditions that their presence can lead the emergency clinician to “explain away” the child’s more serious symptoms as being due to those pathophysiologic findings. Anchoring on a simpler, less severe diagnosis can result in missing or delaying the correct diagnosis.

6. “The patient likely has viral meningitis, so we don't need to get a lumbar puncture.”

The notion that emergency clinicians can distinguish the difference between viral and bacterial meningitis based on the history and physical examination is not supported by the available evidence. The clinical overlap of these conditions is substantial, particularly early in the course of illness. Diagnosis should not be made based on the history and physical examination alone.

8. “We need to wait for a CT scan and lumbar puncture before we can give antibiotics, as they can cause sterilization of CSF.”

When caring for a patient with a presumptive diagnosis of bacterial meningitis, do not delay administration of appropriate antibiotics for the completion of a CT scan or lumbar puncture or for the results of these studies. Although antibiotics may obscure the ultimate bacteriologic diagnosis, this is a small clinical price to pay to prevent further bacterial proliferation and inflammation within the CNS.

Tables

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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Bacterial Meningitis Score for Children

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Critical Actions
• Instructions
• Evidence Appraisal
• Calculator Creator
• References

Introduction

The bacterial meningitis score for children rules out bacterial meningitis in pediatric patients with suspected meningitis.

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Points & Pearls

• The bacterial meningitis score (BMS) predicts bacterial versus aseptic etiology of meningitis in patients aged 29 days to 19 years with suspected meningitis.
• The BMS can help determine if the patient will require admission for parenteral antibiotics while awaiting cerebrospinal fluid (CSF) culture results.
• A higher BMS indicates a higher likelihood of bacterial meningitis.
• Although the score was derived and validated in a population of children aged 29 days to 19 years, the sensitivity, specificity, and negative predictive value (NPV) of the BMS decrease significantly for children aged < 2 months. Therefore, the creators of the BMS advise against using it for children who are aged < 2 months, as well as for children who have already received antibiotics prior to the lumbar puncture, are ill-appearing, or have examination findings that are indicative of an invasive bacterial infection (eg, petechiae and purpura).
• The BMS is not effective at ruling out potentially harmful nervous system infections (eg, herpes encephalitis, Lyme meningitis, tuberculous meningitis) that would require antibiotics.
• Meningococcal meningitis can present without CSF pleocytosis; thus, patients with meningococcal meningitis could be misclassified as not having inclusion criteria for use of the BMS. It is important to perform a thorough physical examination to assess for petechiae or purpura if there is suspicion for meningococcemia or meningococcal meningitis, as the CSF culture may have a false normal result in these cases.

Why and When to Use, and Next Steps

Calculator Review Author

Cullen Clark, MD

Critical Actions

The clinician’s gestalt and the patient’s severity of illness and clinical presentation supersede the application of the BMS. If there is significant suspicion for bacterial meningitis, clinicians should err on the side of caution and admit the patient for observation and empiric antibiotics.

Instructions

The BMS should be used in patients aged 29 days to 19 years who have a CSF white blood cell count of ≥ 10 cells/μL. Do not use the BMS if the patient is critically ill, has recently received antibiotics, has a ventriculoperitoneal shunt or has recently had neurosurgery, is immunosuppressed, or has another bacterial infection that requires antibiotics (including Lyme disease).

Evidence Appraisal

The original BMS was derived from a multicenter retrospective cohort study published by Nigrovic et al in 2007. Data were collected from 20 participating emergency departments at academic medical centers over a 3-year period. The study used the BMS to classify 3295 patients aged 29 days to 19 years who had CSF pleocytosis. Among the 1714 patients who were categorized as very low risk, 2 were found to have bacterial meningitis. Both of the miscategorized patients were aged < 2 months and had E coli meningitis with an E coli urinary tract infection but a negative urinalysis. The sensitivity of the BMS for bacterial meningitis was 98.3% (95% confidence interval [CI], 94.2%-99.8%) and the NPV was 99.9% (95% CI, 99.6%-100%). The investigators attempted to refine the score using recursive partitioning, which led to a simpler model with only 3 variables, but also led to 1 additional patient with meningitis being misclassified as very low risk.

Given that the 2 misclassified patients were aged < 2 months, the investigators analyzed the BMS for a subgroup of all patients aged < 2 months and found that the sensitivity was 92.3% (95% CI, 74.9%-99.4%) and the NPV was 99.5% (95% CI, 98.3%-99.9%). The BMS was validated by Nigrovic et al in 2012, in a meta-analysis of studies published between 2002 and 2012 that included 4896 patients aged 29 days to 19 years. The sensitivity for bacterial meningitis was 99.3% (95% CI, 98.7%-99.7%) and the NPV was 98.3% (95% CI, 96.6%-99.3%).

In 2013, Kulik et al published a systematic review of several bacterial meningitis predictive rules. Among the studies reviewed, the authors found that the BMS had the highest quality of evidence and the best performance to date, but they still recommended that the score be further evaluated with prospective trials.

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Lise Nigrovic, MD, MPH

References H4

Original/Primary Reference

• Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297(1):52-60. DOI: https://doi.org/10.1001/jama.297.1.52

Validation

• Nigrovic LE, Malley R, Kuppermann N. Meta-analysis of bacterial meningitis score validation studies. Arch Dis Child. 2012;97(9):799-805. DOI: https://doi.org/10.1136/archdischild-2012-301798

Other References

• Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivariate predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenza era. Pediatrics. 2002;110(4):712-719. https://www.ncbi.nlm.nih.gov/pubmed/12359784
• Kulik DM, Uleryk EM, Maguire JL. Does this child have bacterial meningitis? A systematic review of clinical prediction rules for children with suspected bacterial meningitis. J Emerg Med. 2013;45(4):508-519. DOI: https://doi.org/10.1016/j.jemermed.2013.03.042

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