Podcast
Questions and Answers
What is the most common cause of community-acquired bacterial meningitis?
What is the most common cause of community-acquired bacterial meningitis?
Which statement accurately differentiates between community-acquired and nosocomial bacterial meningitis?
Which statement accurately differentiates between community-acquired and nosocomial bacterial meningitis?
Which of the following bacteria is least likely to cause bacterial meningitis in individuals over 50 years old?
Which of the following bacteria is least likely to cause bacterial meningitis in individuals over 50 years old?
What is the primary benefit of routine vaccinations in children concerning bacterial meningitis?
What is the primary benefit of routine vaccinations in children concerning bacterial meningitis?
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What is the role of pharmacokinetics and pharmacodynamics in the treatment of central nervous system infections?
What is the role of pharmacokinetics and pharmacodynamics in the treatment of central nervous system infections?
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Which of the following pathogens are most commonly associated with nosocomial meningitis?
Which of the following pathogens are most commonly associated with nosocomial meningitis?
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What is a severe complication that can arise from meningococcal disease?
What is a severe complication that can arise from meningococcal disease?
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Which population is at the highest risk for developing meningococcal meningitis?
Which population is at the highest risk for developing meningococcal meningitis?
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What percentage of patients typically present with the classic triad of fever, neck stiffness, and altered mental status in meningitis cases?
What percentage of patients typically present with the classic triad of fever, neck stiffness, and altered mental status in meningitis cases?
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Which symptom may indicate a meningococcal infection when observed in patients?
Which symptom may indicate a meningococcal infection when observed in patients?
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What condition can occur during acute illness in patients with acute meningitis?
What condition can occur during acute illness in patients with acute meningitis?
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Which provocative maneuver is typically unreliable for ruling out meningitis despite being used as part of the examination?
Which provocative maneuver is typically unreliable for ruling out meningitis despite being used as part of the examination?
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Which clinical sign indicates involuntary flexion of the hip and knee when lifting the head while lying supine?
Which clinical sign indicates involuntary flexion of the hip and knee when lifting the head while lying supine?
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What is the purpose of performing a noncontrast head CT prior to a lumbar puncture?
What is the purpose of performing a noncontrast head CT prior to a lumbar puncture?
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What is the normal opening pressure in cerebrospinal fluid for bacterial meningitis?
What is the normal opening pressure in cerebrospinal fluid for bacterial meningitis?
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At which point should empiric antibiotics be administered in suspected cases of bacterial meningitis?
At which point should empiric antibiotics be administered in suspected cases of bacterial meningitis?
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What is the typical glucose level in cerebrospinal fluid during a bacterial meningitis infection?
What is the typical glucose level in cerebrospinal fluid during a bacterial meningitis infection?
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What should be done if a lumbar puncture is delayed for any reason?
What should be done if a lumbar puncture is delayed for any reason?
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In a case of suspected pneumococcal meningitis, when should dexamethasone be administered?
In a case of suspected pneumococcal meningitis, when should dexamethasone be administered?
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Which of the following substances is typically elevated in cerebrospinal fluid during bacterial meningitis?
Which of the following substances is typically elevated in cerebrospinal fluid during bacterial meningitis?
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What should be measured during a lumbar puncture to aid in the diagnosis of bacterial meningitis?
What should be measured during a lumbar puncture to aid in the diagnosis of bacterial meningitis?
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What is a primary reason for optimizing antibiotic dosing in patients requiring CNS penetration?
What is a primary reason for optimizing antibiotic dosing in patients requiring CNS penetration?
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Which of the following factors does NOT influence antibiotic pharmacokinetics in the CSF?
Which of the following factors does NOT influence antibiotic pharmacokinetics in the CSF?
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How does the inflammatory response in meningitis affect the blood-brain barrier?
How does the inflammatory response in meningitis affect the blood-brain barrier?
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Which antibiotics exhibit similar pharmacodynamics in the CSF as in serum?
Which antibiotics exhibit similar pharmacodynamics in the CSF as in serum?
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What happens to CSF production rates in cases of meningitis?
What happens to CSF production rates in cases of meningitis?
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Which of the following agents' pharmacodynamics is different in the CSF compared to serum?
Which of the following agents' pharmacodynamics is different in the CSF compared to serum?
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What is the role of endothelial tight junctions in the blood-brain barrier?
What is the role of endothelial tight junctions in the blood-brain barrier?
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Which protein binding characteristic is important in determining the pharmacokinetics of antibiotics in the CSF?
Which protein binding characteristic is important in determining the pharmacokinetics of antibiotics in the CSF?
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What does an increase in pinocytotic vesicle formation in meningitis indicate?
What does an increase in pinocytotic vesicle formation in meningitis indicate?
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Study Notes
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
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A serious bacterial infection of the meninges (membrane surrounding the brain and spinal cord)
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Can be life-threatening
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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
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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)
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Common community-acquired pathogens impacting other age groups
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Routine childhood vaccinations have reduced infections
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Common causes of nosocomial meningitis include Staphylococcus aureus, coagulase-negative staphylococci (including methicillin-resistant strains), and gram-negative bacilli (especially Enterobacteriaceae).
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Complications include septic shock, increased intracranial pressure (ICP), syndrome of inappropriate diuresis (SIAD), focal neurologic deficits, hearing loss, and cognitive impairments.
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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).
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Description
Test your knowledge on bacterial meningitis, focusing on its causes, differentiation between community-acquired and nosocomial types, and the significance of vaccinations. This quiz covers various aspects including complications, symptoms, and high-risk populations.
