Bacterial Meningitis Past Paper PDF - King Salman International University

Field of Pharmacy Sciences Bachelor of pharmacy Pharm-D program (Clinical Pharmacy) Pharmacotherapy II PPP407 Fall semester 2024-2025 Date : October 2024  Bacterial Me...

Field of Pharmacy Sciences Bachelor of pharmacy Pharm-D program (Clinical Pharmacy) Pharmacotherapy II PPP407 Fall semester 2024-2025 Date : October 2024  Bacterial Meningitis Dr. Islam Ahmed Assistant Lecturer of Pharmacy Practice & Clinical Pharmacy MSc of Clinical Epidemiology & Clinical Trials Management, Faculty of Medicine, Suez-Canal University MSc of Pharmacy Practice & Clinical Pharmacy, Faculty of Pharmacy, DMU University Doctor of Clinical Pharmacy (PharmD), Faculty of Pharmacy, Alexandria university Bachelor of Pharmaceutical Sciences, Faculty of Pharmacy, Alexandria university  Bacterial Meningitis 1. Interpret signs, symptoms, and laboratory and other relevant diagnostic test results. 2. Assess pharmacotherapies for central nervous system infections, including antimicrobial spectrum of activity, pharmacokinetics, and pharmacodynamics. 3. Select the most appropriate pharmacotherapeutic plan and monitoring based on patient- and disease-specific information, antibiogram data, and best available evidence. 4. Identify preventive therapies for central nervous system infections. BACKGROUND  BACKGROUND ❑ Bacterial meningitis refers to bacterial infection of the meninges resulting in inflammation that can be life-threatening. ▪ Community-acquired bacterial meningitis is caused by invasion of the CNS by bacteria in the setting of bacteremia or by direct extension though dural defects or local infection. ▪ Nosocomial or postsurgical bacterial meningitis occurs after manipulation of the CNS space allowing for entry of pathogenic organisms. ▪ Community-acquired bacterial meningitis is most commonly due to A- Streptococcus pneumoniae (about 50%) B- Neisseria meningitidis (about 30%). C- Listeria monocytogenes accounts for about 5% of cases and is more common in those > 50 years old and immunocompromised patients.  BACKGROUND ▪ Routine childhood vaccination against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis have significantly reduced the incidence of infections. ▪ For nosocomial meningitis, the most common causes are Staphylococcus aureus, coagulase-negative staphylococci (including methicillin-resistant strains), and gram- negative bacilli (especially Enterobacteriaceae). ❑ Complications: Septic shock - Increased intracranial pressure (ICP) - Syndrome of inappropriate diuresis (SIAD) during acute illness - Focal neurologic deficits - Hearing loss - Cognitive impairment after recovery - Purpura fulminans!! BACKGROUND CT of the brain showing diffuse swelling in a patient with meningococcal meningitis. BACKGROUND Purpura fulminans is a severe complication of meningococcal disease. Meningococcal-induced microvascular thrombosis and disseminated intravascular coagulation (DIC) produces widespread hemorrhage into the skin, evolving into painful purple papules which may become necrotic, with the formation of bullae and vesicles.  BACKGROUND ❑ Risk factors: ▪ Age (Extremes of age: infants, elderly) ▪ Community setting (Exposure to large groups (crowding): schools, college dormitories) ▪ Medical conditions/procedures (Cochlear implants, HIV, immunocompromising conditions, asplenia) ▪ Others (Travel, occupational exposure, microbiology lab workers)  CLINICAL PRESENTATION ❑ Prompt diagnosis and management is critical to avoid significant morbidity and mortality. ❑ Presenting signs and symptoms vary. ▪ Presentation can be indolent at the extremes of age, in patients with immunocompromise, and in patients with partially treated infections. ▪ A small percentage of patients experience fulminant bacterial meningitis, with sudden onset, rapid deterioration, abrupt cerebral edema, intracranial hypertension, and brain herniation. ▪ A classic triad of fever, neck stiffness (nuchal rigidity), and altered mental status is seen in about 40% of patients, although it is more common in the elderly and in those with pneumococcal meningitis. ▪ A rapidly evolving petechial or purpuric rash may indicate meningococcal disease. ▪ Brudzinski and Kernig signs of meningeal irritation may help the diagnosis but appear unreliable for ruling out of meningitis.  CLINICAL PRESENTATION Provocative maneuver assessing for signs of meningitis. Patient lying supine; hip flexed to 90 degrees; leg extension at knee with hip flexed is resisted by patient, causing pain in low back; POSITIVE Kernig sign.  CLINICAL PRESENTATION Patient lying supine; lift the head flexing it toward the chest, the maneuver may cause involuntary flexion of the patient's hip and knee ---- POSITIVE Brudzinski sign.  DIAGNOSIS ❑ Testing prior to lumbar puncture (LP): 1. Blood cultures 2. Complete blood count 3. Coagulation studies. 4. Noncontrast head CT prior to LP to assess for the risk of herniation if the patient is ✓ Immunocompromised ✓ Papilledema ✓ History of CNS disease ✓ Focal neurologic deficit ✓ New-onset seizure ≤ 1 week prior ✓ Abnormal level of consciousness. DIAGNOSIS  DIAGNOSIS ❑ Diagnosis is confirmed by LP. ▪ Perform in all patients unless contraindicated. ▪ Consider initiation of empiric antibiotics once the blood cultures are drawn if LP is delayed for any reason (head CT, reversal of anticoagulation, thrombocytopenia, etc). ▪ Measure: ▪ Opening pressure, usually > 180-200 mm H2O in bacterial meningitis ▪ Cell counts with differential, usually > 1 × 109 /L in bacterial meningitis ▪ Cerebrospinal fluid (CSF) glucose, usually low ▪ CSF protein, usually high ▪ CSF for immediate Gram stain and bacterial cultures ▪ Herpes simplex virus (HSV) by PCR, as HSV meningoencephalitis can present in a similar fashion to bacterial meningitis. DIAGNOSIS  MANAGEMENT 1. ANTIBIOTICS ❑ Timing of antibiotic therapy: ▪ IDSA guideline for management of bacterial meningitis recommendations ▪ Start antibiotic therapy as soon as possible after diagnosis of bacterial meningitis is suspected or proven ▪ Dexamethasone beginning 10-20 minutes before or during antibiotic administration in cases of suspected pneumococcal meningitis ▪ Start empiric antibiotics if ▪ LP delayed or head CT required before LP. ▪ Purulent meningitis (even if negative CSF Gram stain). ▪ Empirical Acyclovir (10mg/kg IV every 8 hours) for all patients with suspected encephalitis while awaiting results of diagnostic workup.  MANAGEMENT ❑ Empirical antibiotic therapy:  MANAGEMENT ❑ Antibiotic Dosing:  MANAGEMENT ❑ Duration of Antibiotics: ❑ Outpatient antibiotic therapy is recommended for selected patients to finish antibiotic therapy as outpatient if clinically stable and received inpatient antibiotic for ≥ 6 days.  MANAGEMENT ❑ Antibiotic selection/dosing considerations: A. Optimization of antibiotic dosing is crucial B. Higher doses needed to ensure adequate CNS penetration across blood-brain barrier C. Selection of agent and dosing based on: ▪ 1. Antibiotic pharmacokinetics ▪ 2. Pharmacodynamics of antibiotics in the CNS ▪ 3. Available experimental/clinical data on penetration of specific agents  MANAGEMENT ❑ Blood Brain Barrier (BBB): ▪ Functional barrier. ▪ Controls access of serum components to neuronal tissue. ▪ Endothelial tight junctions limit access into CSF and brain tissue ▪ Alterations of BBB in meningitis - Host inflammatory response mediated by cytokines, and free radicals resulting in: 1. Increased permeability of the BBB to various substances including antibiotics 2. Increase in pinocytotic vesicle formation AND separation of intercellular tight junctions 3. Inflammatory response leads to increased permeability and separated tight junctions MANAGEMENT  MANAGEMENT ❑ Cerebral spinal fluid (CSF): Ultrafiltrate of plasma in a pulsatile flow. ❑ CSF Alterations in meningitis: CSF production rates may be unaltered or decreased - CSF outflow through subarachnoid granulations is reduced - May contribute to prolonged half- lives (t1/2) of drugs in the CSF.  MANAGEMENT ❑ Antibiotic pharmacokinetics in CSF: 1. Lipophilicity 2. Protein binding 3. Molecular weight 4. Active transport mechanisms 5. CNS inflammation 6. Infecting organism ❑ Antibiotic pharmacodynamics in CSF: ▪ Aminoglycosides and fluoroquinolones appear to exhibit similar pharmacodynamics in the CSF as in the serum (Concentration-dependent killing and Post-antibiotic effect). ▪ β-lactams may display concentration-dependent killing !! and a post-antibiotic effect against Gram-negative organisms (Based on experimental meningitis or in vitro data).  MANAGEMENT ❑ Intrathecal and intraventricular ▪ Adjunctive therapy for antibiotics with poor CNS penetration, poor IV response, MDR organism. ▪ Recommended for polymyxins, aminoglycosides, vancomycin, daptomycin but avoided with β-lactams (very high risk of seizures). ▪ Solutions should closely match physiologic pH (7.31) and osmolality (281 mOsm/kg) of CSF. ▪ Avoid medications formulated with preservatives ▪ Administration via ventricular drain – limited volume 5-10 mL - Clamp 15-60 minutes - Usually used once daily. ▪ Adverse effect - Neurotoxicity (e.g., aseptic meningitis, myelopathy, acute/subacute encephalopathy, seizures).  MANAGEMENT 2. Steroids: ▪ Dexamethasone (0.15 mg/kg IV every 6 hours for 2-4 days) may reduce associated cerebral edema, increased ICP, altered cerebral blood flow, cerebral vasculitis, and neuronal injury by decreasing inflammatory response, but does not reverse damage that occurred prior to treatment. ▪ In all adults with suspected or proven pneumococcal, even if highly resistant to reduce mortality. ▪ Give first dose 10-20 minutes before or with first antibiotic dose. Do NOT give to adults who have already received antibiotic therapy because it is unlikely to improve outcome. ❑ Rifampin: Recommended when steroids given as vancomycin may not adequately penetrate the BBB (steroids reduce inflammation).  ANTIBACTERIAL PROPHYLAXIS ❑ Several types of bacterial meningitis can be prevented with antibiotic prophylaxis given to persons coming into contact with infected individuals. ❑ S. Pneumoniae ---- NO prophylaxis. (CDC guidelines) ❑ Hib ---- use Rifampin 20 mg/kg (max: 600 mg) oral once daily x 4 days. ❑ Streptococcus agalactiae ---- Pregnant women with high risk for invasive group B strep (GBS) use Intra-partum IV penicillin G 5 MUx1, then 2.5-3 MU every 4hr until delivery OR Ampicillin 2 g every 4 hr until delivery. ❑ N. meningitidis (Meningococcal meningitis): ▪ Droplet precautions for hospitalized patients as soon as diagnosis is suspected. ▪ Chemoprophylaxis for close contacts ✓ Rifampin (600 mg orally / 12 hours for 2 days) ✓ Ciprofloxacin (500 mg orally once) ✓ Ceftriaxone (250 mg intramuscularly once) CASE STUDIES  CASE. 1 EB is a 7-year-old male patient presenting to the ED with fevers and complaints of a headache and vomiting. His parents report that the patient has not been his ”normal self” (increased irritability) for the past 48 hours. Of note, the patient completed a 10-day course of Amoxicillin-clavulanate approximately 21 days ago for acute otitis media. The patient’s past medical history is notable for cochlear implants, he is up to date on his vaccines, and he has no known drug allergies. Pertinent labs/vitals on admission: Basic metabolic panel: Within normal limits Complete blood count: Notable for a WBCs count of 13.2 × 10*3 cells /mm3 All other values within normal limits Vitals: o Temp: 38.8 °C o BP: 101/63 mm Hg o HR: 70 beats/min o RR: 22 breaths/min  CASE. 1 The LP results are reported the following day: o Opening pressure: 210 mm H20 o CSF analysis WBC (cells/mm3) = 1800 Cell type differential = Lymphocytes 4%, Monocytes 1%, Neutrophils 95%, Eosinophils 0% Glucose (mg/dL) = 25 Protein (mg/dL) = 100  CASE. 1 Q1. Which of the following LP results suggests that this patient has bacterial meningitis? A. High glucose, high protein, and high white blood cell count with neutrophil predominance B. Low glucose, high protein, and high white blood cell count with neutrophil predominance C. Low glucose, high protein, and low white blood cell count with neutrophil predominance D. Low glucose, low protein, and high white blood cell count with neutrophil predominance  CASE. 1 Q2. What are the most likely organisms that may be involved in this case? A. L. monocytogenes and Klebsiella spp. B. S. pneumoniae and N. meningitidis. C. S. pneumoniae and E. coli. D. L. monocytogenes, Gram-negative bacilli.  CASE. 1 Q3. Which of the following antibiotic regimens would be most appropriate to initiate for EB to treat his bacterial meningitis? A. Ampicillin 200 mg/kg/day in divided doses Q3H to Q4H + gentamicin 4.5 to 7.5 mg/kg/day once daily B. B. Ceftriaxone 100 mg/kg/day in divided doses Q12H + vancomycin 60 mg/kg/day in divided doses Q6H to Q8H C. C. Meropenem 120 mg/kg/day divided Q8H + gentamicin 4.5 to 7.5 mg/kg/day once daily D. D. Cefazolin 100 mg/kg/day divided Q8H + vancomycin 60 mg/kg/day in divided doses Q6H to Q8H  CASE. 1 Q4. Which of the following characteristics improves CNS penetration of antibiotics? A. High lipophilicity B. High protein binding C. High molecular weight D. High polarity (carrying a charge at physiologic pH)  CASE. 1 Q5. Which of the following statements about the use of corticosteroids in bacterial meningitis is correct?? A. They should be administered to adult and pediatric patients with confirmed CSF cultures growing N. meningitidis for 2-4 days. B. They should be administered to patients of all ages and should be continued the entire course of antibiotic treatment. C. They should not be administered because they interfere with antibiotic penetration into the CSF. D. They should be administered in pediatric patients with suspected or confirmed H. influenzae meningitis and continued a total of 2-4 days. ANY QUESTIONS ?