Bacterial Meningitis

Afeerah Mumtaz (1), Junaid S Kalia (2)
1 - King Edward Medical University
2 - Founder AINeuroCare.com


Introduction

  • Meningitis refers to the presence of inflammation in the meninges (membranes surrounding the brain and spinal cord)
  • It can be infectious or non-infectious
  • Infectious meningitis could be due to bacterial,viral or fungal
  • Non-infectious meningitis could be chemical (anesthetics,blood) or idiopathic
  • Bacterial meningitis can be acute or chronic
  • It is relatively uncommon in the United States due to widespread use of vaccines
  • Globally it is a serious problem in developing countries like Sub-Saharan Africa (incidence rate 101 per 10,000 populations in the period 1981 to 1996 in Niger)
  • With the use of vaccines, a dramatic decline in Haemophilus Influenzae type b (Hib) and pneumococcal meningitis has been reported.

Pathophysiology

  • Bacteria gain entry into the human body and follow different pathways to gain access to meninges and the brain.
  • Blood brain barrier naturally protects the brain from the body's immune system. In meningitis, this barrier is disrupted as a result of the ongoing inflammatory process
  • Depending upon the severity of infection, the inflammatory process may remain confined to subarachnoid space.
    • In less severe forms, pial barrier is not breached and parenchyma is spared the injury
    • In more severe forms, inflammatory process spreads to the underlying parenchyma and leads to cortical destruction particularly when, left untreated

Etiology

  • Causative organisms for community acquired bacterial meningitis are classified according to age, as follows
  • Healthcare associated bacterial meningitis is mostly caused by Staphylococcus aureus and Gram negative bacilli (including propionibacterium acnes and pseudomonas species)

Table 1: Etiology of bacterial meningitis according to age

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Derived from: Allana Sucher, C., 2021. Treatment and Prevention of Community-Acquired Bacterial Meningitis

Risk Factors

  • Factors predisposing community acquired meningitis include;
    • Skipping vaccinations
    • Living in a community setting
    • Pregnancy
    • Compromised immune system
    • Younger age esp under 5
    • Asplenic patients
    • Travel to the areas (such as Africa) where meningitis is endemic
    • Military recruits
  • Interventions like CSF shunts, CSF drains, implantation of intrathecal infusion pumps, implantation of deep brain stimulation hardware and general neurosurgery put patients at risk of healthcare-associated bacterial meningitis.

Clinical Manifestations

  • The classic triad for bacterial meningitis includes
Fever
Neck stiffness
Altered mental status
However, it is present in less than 50% of the patients with bacterial meningitis
  • Other symptoms includes
Malaise
Headache
Photophobia
Phonophobia
Vomiting
Confusion
Seizures
Sleepiness or difficulty waking
Skin rash (sometimes as in meningococcal meningitis)
  • Meningeal irritation (meningismus) is present at physical examination as neck stiffness, the Kernig sign and the Brudzinski sign
  • Meningismus could be absent very early in disease,in deeply comatose patients and in immunocompromised patients such as with liver cirrhosis
  • 33% of the patients develop focal neurological signs such as epileptic seizures or paresis of a limb
  • 69% of the patients present with impaired consciousness(defined as a score of <14 on Glasgow Coma Scale)
  • 14% of the patients develop coma
  • In infants, presentation is usually non-specific that includes
  • Non Specific Fever
  • Lethargy
  • Poor feeding
  • Inconsolableness
  • Hypertonia or hypotonia
  • Respiratory distress
  • Bulging fontanelle may be present
  • Meningeal signs are usually absent
  • Fever affects less than 40% and seizures affect less than 35% of infected babies

Diagnosis

  • CSF Analysis:
  • Proof of bacteria in CSF by either Gram staining or positive culture is key to diagnosis of bacterial meningitis.
  • CSF culture is gold standard for detecting causative pathogens. However it’s time-consuming and final results are not available before 48h or more.
  • CSF gram staining is a rapid method and has great specificity
  • PCR has an important role in detection of meningococcal infection
  • Latex agglutination-based rapid tests are available but have imperfect sensitivity and specificity.
  • CSF cytology and chemistry is also altered in meningitis and provides a great help in differentiating bacterial from other infectious meningitis
  • Low CSF white blood cell count may confound the diagnosis in bacterial meningitis of immunocompromised patients, patients with leukopenia or in overwhelming bacterial infection (apurulent bacterial meningitis). This further emphasizes the importance of CSF culture and gram stain
  • Peripheral WBCs, ESR, serum C-reactive protein, procalcitonin and other acute phase proteins are elevated in bacterial meningitis but are of limited diagnostic value
  • A cranial CT provides information about intracranial complications (such as brain edema, hydrocephalus).
  • Bone window imaging identifies parameningeal foci such as sinusitis, odontogenic abscess,and mastoiditis. Such local infections may require surgical repair.
  • Some studies suggest performing CT before lumbar puncture in order to rule out the risk of herniation due to increased intracranial pressure. This is particularly important in patients presenting with focal
neurologic deficits
seizures
altered state of consciousness

Table 2: Characteristics assessed to diagnose bacterial, viral and tuberculous meningitis

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Derived from: van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016 Nov 3;2:16074. doi: 10.1038/nrdp.2016.74. PMID: 27808261

Management

  • Patients presenting with unstable vital signs or acute complications( like altered mental status, seizures) must be treated in an intensive care unit with expertise in neurological diseases and need to be stabilized first.
  • Next step should be the prompt initiation of empiric antibiotic therapy as appropriate for the patient's age and condition.
  • After identification of pathogens and determination of susceptibilities ,targeted antibiotic therapy must be given.

Table 3: Vital stabilization of patients with acute bacterial meningitis

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Derived from: Hasbun, R., 2019. Meningitis: Practice Essentials, Background, Pathophysiology.

Table 4: Empiric antibiotic therapy in acute bacterial meningitis

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Ceftriaxone administered 8-12g/day every 4-6 hours or administered at 4g/day every 12 hours; Vancomycin 30-60mg/kg/day
Derived from : Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23(3):467-492. doi:10.1128/CMR.00070-09

Table 5: Specific antibiotic therapy according to pathogen

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Derived from : Hauser, S. and Josephson, S., 2013. Harrison's Neurology in Clinical Medicine, 3E. New York: McGraw-Hill Publishing

Complications

  • Bacterial meningitis is a neurological condition with high morbidity and mortality.
  • Adjunctive dexamethasone therapy has been shown to reduce the unfavorable outcomes and death. However, neurological complications occur in 30% of survivors.
  • Delayed initiation of antibiotic therapy has been shown to significantly increase mortality and adverse outcomes at 3 months
  • Common complications include;
    • Neurological
      • Hydrocephalus
      • Ischemic infarction
      • Cerebral hemorrhage
      • Hearing loss
      • Memory difficulty
      • Learning disabilities
      • Brain damage
      • Gait problems
      • Seizures
      • SIADH
    • Non-neurological
      • Organ failure (such as kidney,adrenals etc)
      • Disseminated intravascular coagulation (DIC)
      • Shock
      • Death

Table 6: Complications and outcome of bacterial meningitis cases.

notion image
Derived: Sunwoo JS, Shin HR, Lee HS, Moon J, Lee ST, Jung KH, Park KI, Jung KY, Kim M, Lee SK, Chu K. A hospital-based study on etiology and prognosis of bacterial meningitis in adults. Sci Rep. 2021 Mar 16;11(1):6028. doi: 10.1038/s41598-021-85382-4. PMID: 33727651; PMCID: PMC7966379

Prevention

  • General measures required to prevent bacterial meningitis include the following;
    • Practice good hygiene
    • Cover your mouth
    • If pregnant,eat healthy foods
    • Avoid sharing utensils with someone having meningitis
    • Take contact precautions (avoid sneezing ,coughing,kissing)
  • Vaccines are available as an efficient means for prevention of bacterial meningitis.
  • Haemophilus influenzae type b (Hib) vaccine: given to children as part of childhood vaccination between age 2 months and 15 months
  • Pneumococcal conjugate vaccine (PCV13): part of routine childhood vaccination. Given under age 2. Additional doses are given to children at high risk between age 2 and 5
  • Pneumococcal polysaccharide vaccine (PPSV23): given to all adults older than age 65. Older children and adults (those with chronic illnesses or weaker immune systems)
  • Meningococcal conjugate vaccine: recommended 1st dose between age 11 and 12. Booster shots are given at age 16. If the first dose is given between age 13 and 15, a booster shot is given between age 16 and 18. No booster shot is needed when the first dose is given after age 16.
  • Chemoprophylaxis is needed in close contacts of someone with meningococcal meningitis
  • Recommended antibiotics for prophylaxis include Rifampin, Ceftriaxone. Ciprofloxacin is also effective in some cases.
  • Prophylaxis is also recommended for close contacts of someone with serious Hib infection
  • Especially when the contacts are at increased risk based upon age,immunocompromised status or vaccination status. Rifampin is given for Hib prophylaxis

Further Reading

  • Liora ter Horst, Matthijs C Brouwer, Arie van der Ende, Diederik van de Beek, Recurrent Community-Acquired Bacterial Meningitis in Adults, Clinical Infectious Diseases, 2020;, ciaa1623, https://doi.org/10.1093/cid/ciaa1623
  • H. Schmidt, B. Heimann, M. Djukic, C. Mazurek, C. Fels, C.-W. Wallesch, R. Nau, Neuropsychological sequelae of bacterial and viral meningitis, Brain, Volume 129, Issue 2, February 2006, Pages 333–345, https://doi.org/10.1093/brain/awh711

Bibliography

  • Hasbun, R., 2019. Meningitis: Practice Essentials, Background, Pathophysiology. [online] Emedicine.medscape.com. Meningitis Available at: <https://emedicine.medscape.com/article/232915-overview#a3>
  • Mayo Clinic. 2021. Meningitis - Symptoms and causes. [online] Available at: <https://www.mayoclinic.org/diseases-conditions/meningitis/symptoms-causes/syc-20350508>
  • Dyckhoff-Shen S, Koedel U, Pfister HW, Klein M. SOP: Emergency workup in patients with suspected acute bacterial meningitis. Neurol Res Pract. 2021;3(1):2. Published 2021 Jan 7. doi:10.1186/s42466-020-00098-6
  • Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23(3):467-492. doi:10.1128/CMR.00070-09
  • Hoffman O, Weber RJ. Pathophysiology and treatment of bacterial meningitis. Ther Adv Neurol Disord. 2009;2(6):1-7. doi:10.1177/1756285609337975
  • Van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016 Nov 3;2:16074. doi: 10.1038/nrdp.2016.74. PMID: 27808261
  • Sunwoo JS, Shin HR, Lee HS, Moon J, Lee ST, Jung KH, Park KI, Jung KY, Kim M, Lee SK, Chu K. A hospital-based study on etiology and prognosis of bacterial meningitis in adults. Sci Rep. 2021 Mar 16;11(1):6028. doi: 10.1038/s41598-021-85382-4. PMID: 33727651; PMCID: PMC7966379.
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