Bacterial Meningitis Quiz

Pharmacotherapy II (PPP407)

• Course offered by King Salman International University
• Bachelor of Pharmacy Pharm-D program (Clinical Pharmacy)
• Fall semester 2024-2025
• Date: October 2024

Bacterial Meningitis

• A serious bacterial infection of the meninges (membrane surrounding the brain and spinal cord)

• Can be life-threatening

• Classification:

  • Community acquired: caused by bacterial invasion of the CNS via bacteremia or direct extension through dural defects or local infection
  • Nosocomial/post-surgical: occurs after CNS manipulation allowing pathogen entry

• Common causative organisms for community-acquired meningitis:

  • Streptococcus pneumoniae (about 50%)
  • Neisseria meningitidis (about 30%)
  • Listeria monocytogenes (about 5%, more common in >50 years old and immunocompromised)

• Common community-acquired pathogens impacting other age groups

• Routine childhood vaccinations have reduced infections

• Common causes of nosocomial meningitis include Staphylococcus aureus, coagulase-negative staphylococci (including methicillin-resistant strains), and gram-negative bacilli (especially Enterobacteriaceae).

• Complications include septic shock, increased intracranial pressure (ICP), syndrome of inappropriate diuresis (SIAD), focal neurologic deficits, hearing loss, and cognitive impairments.

• Complications also include purpura fulminans (severe complication of meningococcal disease)

Diagnosis

• Testing prior to lumbar puncture (LP): blood cultures, complete blood count (CBC), coagulation studies
• Non-contrast head CT before LP to assess for herniation if patient is immunocompromised, has papilledema, CNS history, focal neurologic deficits, new onset seizures, or altered consciousness
• CSF analysis:
  • Opening pressure: usually >180-200mm Hg in bacterial meningitis
  • Cell count with differential usually > 1x10^9/L in bacterial meningitis
  • CSF glucose usually low
  • CSF protein usually high
• Herpes simplex virus (HSV) can be identified with PCR

Clinical Presentation

• Prompt diagnosis and management is critical to avoid significant morbidity and mortality.
• Signs and symptoms can vary, including indolent presentation (at extremes of age, immunocompromised patients, or in patients with partially treated infections)
• A small percentage of patients can present with fulminant bacterial meningitis presenting with sudden onset, rapid deterioration, abrupt cerebral edema, intracranial hypertension, and brain herniation
• A triad of fever, neck stiffness (nuchal rigidity), and altered mental status is seen in approximately 40% cases (most common in elderly and pneumococcal meningitis).
• Petechial or purpuric rash may indicate meningococcal disease
• Brudzinski and Kernig signs may help detect meningeal irritation, but aren't reliable for definitively ruling out meningitis.
• Provocative maneuvers for assessing signs of meningitis include patient lying supine and flexing the hip, maintaining a 90-degree angle, and extending the knee. Resistant extension of the knee, causing pain in the low back area, indicated a positive Kernig sign.

Management

• Antibiotics:
  • Timing: initiate therapy as soon as possible after diagnosis (or if suspected, use empiric antibiotics, especially with delayed LP or if CT required).
  • Dexamethasone: begin 10-20 minutes before or during antibiotic administration for suspected pneumococcal meningitis
  • LP and head CT required if delayed, purulent meningitis or negative CSF Gram stain
  • Empirical Acyclovir (10mg/kg IV every 8 hours): used for all suspected encephalitis, while awaiting diagnostic workup results
• Antibiotic Regimens: empirical antibiotic therapy based on predisposing factors (age, head trauma, etc.)

Antibiotic Dosing

• Specific dosages for various antibiotics categorized by infant/children and adult doses

Duration of Antibiotics

• Recommended duration of antibiotics varies based on organism (N. meningitidis, S. pneumoniae, etc.) and if community-acquired or hospital-acquired
• Outpatient antibiotic therapy is often recommended after inpatient treatment if the patient is clinically stable.

Antibiotic Selection/Dosing

• Optimize antibiotic dosing to ensure adequate CNS penetration
• Select antibiotic based on pharmacokinetics, pharmacodynamics, and available data regarding CNS penetration

Blood Brain Barrier (BBB)

• BBB is a functional barrier that controls access of serum components.
• Endothelial tight junctions restrict access to CSF and brain tissue.
• Alterations of BBB in meningitis occur when inflammatory response (mediated by cytokines and free radicals) leads to altered permeability.
• Increased permeability, increased pinocytotic vesicle formation and separation of intercellular tight junctions occur

CSF

• CSF is an ultrafiltrate of plasma.
• CSF production rates may be unaffected or decreased.
• CSF outflow through subarachnoid granulations may be reduced, thus contributing to prolonged half-life of drugs

Antibiotic Pharmacokinetics in CSF

• Considerations for ensuring adequate CNS penetration include lipophilicity, protein binding, molecular weight, active transport, and CNS inflammation.

Intrathecal/Intraventricular

• Used as adjunctive therapy for poor CNS penetration, IV response & MDR organisms; should be avoided with B-lactams because of potential seizure risk, while also considering CSF pH and osmolality match, and limited volumes administer using the ventricular drain.
• Consider neurotoxicity risks for potential adverse effects

Steroids

• Dexamethasone (0.15 mg/kg IV every 6 hrs for 2-4 days) may reduce cerebral edema, increased ICP, altered cerebral blood flow, and potential cerebral vasculitis and neuronal injury.
• Give first steroid dose 10-20 minutes prior, or with the first antibiotic dose; steroids should not be given if the patient has already received antibiotic therapy.

Antimicrobial Prophylaxis

• Prevention through antibiotic prophylaxis for close contacts, droplet precautions for hospitalized patients suspected for bacterial infections, and specific prophylaxis regimens based on the causative agent.

Case Studies

• Case 1 details a 7-year-old male presenting with fever, headache, and vomiting, and a history of suspected pneumococcal meningitis following amoxicillin-clavulanate treatment.
• Pertinent labs show elevated WBCs count
• LP analysis indicated elevated WBC, low glucose, and elevated protein in CSF.

Case Study Questions:

• Q1:* What are the LP results implying? (answer: low glucose & high protein w/ high white blood cell count with neutrophil predominance).
• Q2:* Which pathogens are likely? (answer: S. pneumoniae, N. meningitidis).
• Q3:* Which antibiotic regimen is considered best? (answer: Ceftriaxone 100 mg/kg/day with vancomycin 60 mg/kg/day)
• Q4:* Which bacteria characteristic promotes CNS penetration? (answer: High lipophilicity).
• Q5:* What is correct about the use of corticosteroids in bacterial meningitis? (answer: Give the first dose at least 10-20 minutes before/with the first antibiotic administration. Do not give to patients who have already received antibiotic therapy).