1 / 44

Infectious Disease I: Central Nervous System Infections

Infectious Disease I: Central Nervous System Infections. Courses in Therapeutics and Disease State Management. Learning Objectives (Slide 1 of 3). Define meningitis and  encephalitis

alvaroj
Download Presentation

Infectious Disease I: Central Nervous System Infections

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Infectious Disease I:Central Nervous System Infections Courses in Therapeutics and Disease State Management

  2. Learning Objectives (Slide 1 of 3) • Define meningitis and encephalitis • List, in order of relative incidence, the most common age-dependent bacterial causes of meningitis, and identify the fatality rate associated with each • Analyze laboratory values of CSF components and describe the values as normal or as indicative of a specific infective condition • Identify the common signs and symptoms of bacterial meningitis • Select appropriate empirical therapy directed against suspected bacterial meningitis according to age group

  3. Learning Objectives (Slide 2 of 3) • List the antibiotic of first choice and alternatives to treat meningitis secondary to Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae • Identify general principles of chemoprophylaxis after exposure to H. influenzae and N. meningitidis index cases • List the physiochemical properties associated with increased penetration of antibiotics into the CNS • Classify antibiotics according to level of penetration into the CNS • List three reasons why corticosteroid use in bacterial meningitis is controversial

  4. Learning Objectives (Slide 3 of 3) • Assess the value of dexamethasone as adjunctive therapy in meningitis • Discuss the role vaccination plays in the prevention of meningitis and what impact vaccination is having on the epidemiology of meningitis • Select appropriate antifungal therapy to treat Cryptococcus neoformans • List the viruses most commonly associated with encephalitis and meningoencephalitis and provide recommendations for therapy as appropriate

  5. Required Reading • Elshaboury RH, Hermsen ED, Holt JS, Mitropoulos IF, Rotschafer JC. Chapter 84. Central Nervous System Infections In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. • Tunkel AR, Hartman BJ, Kaplan SL, et.al.. 2004. Practice guidelines for the management of bacterial meningitis. Clin. Infect. Dis. 39:1267-1284. • Tunkel AR, Hasbun R, Bhimraj A, et.al.. 2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017; 64 (6): e34-e65.

  6. Overview (Slide 1 of 2) • Infections involving the brain, spinal cord, and associated tissues, fluids, and membranes • Meningitis • Encephalitis • Brain Abscess • Shunt infections • Postoperative infections • High rates of mortality and morbidity

  7. Overview (Slide 2 of 2) • Community Acquired Meningitis • Healthcare-associated Ventriculitis and Meningitis • Cerebrospinal fluid (CSF) shunts • CSF drains • Intrathecal infusion pumps  • Deep brain stimulation hardware • Neurosurgery or Head Trauma

  8. Pathophysiology • Blood Brain Barrier • Pathogen gain entry to the CNS • Contiguous spread • Hematogenous seeding • Direct inoculation • Reactivation of a latent infection • Damage occurs due to immune response to bacterial cellular components Schematic representation of a blood–cerebrospinal fluid barrier capillary, brain tissue capillary, and normal tissue capillary.

  9. Acute Bacterial Meningitis: Most Common Pathogens • Community Acquired Meningitis • Streptococcus pneumoniae • Group B Streptococcus • Neisseria meningitidis • H. influenzae • Listeria monocytogenes • Healthcare-associated Ventriculitis and Meningitis • Community Acquired Meningitis pathogens • Gram negative bacilli • Staphylococcus aureus • Coagulase-negative staphylococci • Propionibacterium acnes Hypothetical schema of pathophysiologic events that occur during bacterial meningitis. (IL-1, interleukin 1; TNF, tumor necrosis factor; PAF, platelet-activating factor; CBF, cerebral blood flow; CSF, cerebrospinal fluid; PGE2, prostaglandin E2; ICP, intracranial pressure.)

  10. Clinical Presentation, Signs and Symptoms (Slide 1 of 2) • Headache • Fever • Nuchal rigidity • Altered mental Status • Nausea • Focal neurological deficits • Brudzinski’s sign • Kernig’s sign • Seizures • Photophobia • Skin lesions • Petechial rash • Neonates • Altered feeding/ sleeping • Bulging fontanel • Seizures • Irritability/ lethargy

  11. Clinical Presentation, Signs and Symptoms (Slide 2 of 2) Link: Schematic of Brudzinski’s signs Link: Schematic of Kernig’s sign

  12. Laboratory Tests • Lumbar Puncture • Opening Pressure • CSF composition • CSF gram stain • CSF culture • Blood Cultures • Scraping of skin lesions • WBC • Cranial Imaging • Magnetic resonance imaging (MRI) • Computed tomography (CT) scan

  13. Mean Values of the Components of Normaland Abnormal Cerebrospinal Fluid aInitial cerebrospinal fluid (CSF) and while blood cell (WBC) count may reveal a predominance of polymorphonuclear leukocytes (PMNs).

  14. Goals of Therapy • Prevent Death • Prevent residual neurological deficits • Eradicate or control invading organism by starting appropriate antimicrobial therapy • Ameliorate clinical signs and symptoms • Provide supportive care • Prevent future infections through timely introduction of vaccination and chemoprophylaxis

  15. Nonpharmacological Treatment • Respiratory and Circulatory Support as needed

  16. Pharmacological Treatment • Early administration of appropriate antimicrobial therapy • Antimicrobial agents must have sufficient CNS penetration • Initial empiric antimicrobial therapy based on patient specific factors • Focused and targeted antimicrobial therapy once pathogen identified • Supportive Care • Fluids • Electrolytes • Antipyretics • Analgesics

  17. Antimicrobial Penetration into the CSF (Table 1 of 3)

  18. Antimicrobial Penetration into the CSF(Table 2 of 3) *May not achieve therapeutic levels against organisms with higher MIC, as in P. aeruginosa. Tazobactam does not penetrate blood–brain barrier.

  19. Antimicrobial Penetration into the CSF(Table 3 of 3) ⱡCefuroxime is an exception. ◊Documented effectiveness for Borrelia burgdorferi. □Includes clavulanic acid, sulbactam, and tazobactam. ∆ Achieves therapeutic concentrations for Cryptococcus neoformans therapy.

  20. Empiric Therapy: Most Common Pathogens by Age (Slide 1 of 4) • Less than 1 months old • Pathogens • S. agalactiae • E. coli • Klebsiella pneumoniae • Enterobacter spp. • Listeria monocytogenes • Empiric Antibiotics • Ampicillin IV plus cefotaxime IV or ampicillin IV plus aminoglycoside IV

  21. Empiric Therapy: Most Common Pathogens by Age (Slide 2 of 4) • 1-23 months old • Pathogens • Streptococcus pneumoniae • Neisseria meningitidis • H. influenzae • S. agalactiae • Empiric Antibiotics • Vancomycin IV plus third-generation cephalosporin IV (cefotaxime or ceftriaxone)

  22. Empiric Therapy: Most Common Pathogens by Age (Slide 3 of 4) • 2-50 years • Pathogens • Neisseria meningitidis • Streptococcus pneumoniae • Empiric Antibiotics • Vancomycin IV plus third-generation cephalosporin IV (cefotaxime or ceftriaxone)

  23. Empiric Therapy: Most Common Pathogens by Age (Slide 4 of 4) • > 50 years • Pathogens • Neisseria meningitidis • Streptococcus pneumoniae • Listeria monocytogenes • E. coli • Klebsiella pneumoniae • Enterobacter spp. • Empiric Antibiotics • Ampicillin IV plus third-generation cephalosporin IV (cefotaxime or ceftriaxone) plus vancomycin IV

  24. Empiric Therapy: Most Common Pathogen Healthcare-associated Ventriculitis and Meningitis • Pathogens • Community Acquired Meningitis pathogens • Gram negative bacilli • Staphylococcus aureus • Coagulase-negative staphylococci • Propionibacterium acnes • Empiric Antibiotics • Vancomycin IV or Linezolid IV plus ceftazidime IV or cefepime IV, or meropenem IV

  25. Streptococcus pneumoniae Targeted Therapy(Slide 1 of 3) • Penicillin MIC < 0.1 mg/L • Standard Therapy • Penicillin G 4 million units IV Q4H • Ampicillin 2 gm IV Q4H • Alternate Therapies • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • True β-lactam Allergy • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of treatment • 10-14 days

  26. Streptococcus pneumoniae Targeted Therapy (Slide 2 of 3) • Penicillin MIC 0.1-1 mg/L • Standard Therapy • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • Alternate Therapies • Meropenem 2 gm IV Q8H • Cefepime 2 gm IV Q8H • True β-lactam Allergy • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of treatment • 10-14 days

  27. Streptococcus pneumoniae Targeted Therapy (Slide 3 of 3) • Penicillin MIC > 2 mg/L or Ceftriaxone MIC ≥ 1 • Standard Therapy • Ceftriaxone 2 gm IV Q12H PLUS Vancomycin • Cefotaxime 2 gm IV Q4H PLUS Vancomycin • Alternate Therapies • Moxifloxacin 400 mg IV q24H • Duration of treatment • 10-14 days

  28. Neisseria meningitidis Targeted Therapy (Slide 1 of 2) • Penicillin MIC < 0.1 mg/L • Standard Therapy • Penicillin G 4 million units IV Q4H • Ampicillin 2 gm IV Q4H • Alternate Therapies • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of treatment • 7-10 days

  29. Neisseria meningitidis Targeted Therapy (Slide 2 of 2) • Penicillin MIC 0.1-1 mg/L • Standard Therapy • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • Alternate Therapies • Meropenem 2 gm IV Q8H • Cefepime 2 gm IV Q8H • True β-lactam Allergy • Moxifloxacin 400 IV Q24H • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of treatment • 7-10 days

  30. H. influenza Targeted Therapy (Slide 1 of 2) • β-lactamase negative • Standard Therapy • Ampicillin 2 gm IV Q4H • Alternate Therapies • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • Cefepime 2 gm IV Q8H • True β-lactam Allergy • Moxifloxacin 400 IV Q24H • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of Treatment • 7-10 days

  31. H. influenza Targeted Therapy(Slide 2 of 2) • β-lactamase positive • Standard Therapy • Ceftriaxone 2 gm IV Q12H • Cefotaxime 2 gm IV Q4H • Alternate Therapies • Cefepime 2 gm IV Q8H • True β-lactam Allergy • Moxifloxacin 400 IV Q24H • Chloramphenical 50-100 mg/kg/day in divided doses every 6 hours; max daily dose: 4 g/day • Duration of Treatment • 7-10 days

  32. Listeria monocytogenes Targeted Therapy • Standard Therapy • Ampicillin 2 gm IV Q4H • Alternate Therapies • Meropenem 2 gm IV Q8H • True β-lactam Allergy • Trimethoprim/ Sulfamethoxazole IV • 10-20 mg TMP/kg/day in divided doses every 6-12 hours • Duration of Treatment • 21 days

  33. Methicillin Susceptible Staphylococcus Aureus Targeted Therapy • Standard therapy • Nafcillin or Oxacillin 1.5-3 gm IV Q4H • Alternate Therapy • Meropenem 2 gm IV Q8H • True β-lactam Allergy • Vancomycin • Duration of Treatment • 2-3 weeks • 4-6 weeks if shunt involved

  34. Methicillin Resistant Staphylococcus Aureus Targeted Therapy • Standard Therapy • Vancomycin • Alternate Therapy • Trimethoprim/ Sulfamethoxazole • 10-20 mg TMP/kg/day in divided doses every 6-12 hours • Linezolid 600 mg IV Q12H • Duration of Treatment • 3-4 weeks • 4-6 weeks if shunt involved

  35. Cryptococcus neoformans Targeted Therapy • Standard Therapy • Amphotericin B combined with flucytosine for 2 weeks • Alternate Therapy • Amphotericin B • Amphotericin B plus High dose Fluconazole • Amphotericin B plus Voriconazole or Itraconazole • Duration of Treatment • 2 to 6 weeks of induction therapy • 8 weeks of consolidation therapy

  36. Viral Encephalitis and Meningoencephalitis Targeted Therapy • Common Viruses • Herpes simplex virus • West Nile virus • Enteroviruses • Standard Therapy • Acyclovir 10 mg/kg IV Q8H • Alternate Therapy • Foscarnet 120-200 mg/kg IV per day in divided doses every 8-12 hours • Duration of Treatment • 14-21 days

  37. Dexamethasone • Corticosteroids inhibit the production of pro-inflammatory cytokines • Clinical trial data surrounding the benefits of corticosteroids in meningitis is conflicting • A series trials and systematic review showed steroids may improve neurological and mortality outcomes in adult patients • A larger trial showed conflicting data • Various antimicrobial agents were used • Dexamethasone was administered at different times in relation to the first antimicrobial dose • Patients had varying levels of illness severity • Overall use of corticosteroids in the setting of meningitis is controversial

  38. Dexamethasone Recommendations • Infants and children • H. influenza: Dexamethasone 0.15 mg/kg Q6H for 2-4 days • Administer before or concurrently with the first dose of antibiotics • Pneumococcal: not routinely recommended must weigh risk versus benefit • Adults • Pneumococcal: Dexamethasone 10 mg IV Q6H for 2-4 days • Administer before or concurrently with the first dose of antibiotics • Other bacterial causes of meningitis: not routinely recommended

  39. Evaluation of Outcomes • Monitor the following every 4 hours for 3 days • Fever • Headache • Meningismus • Vital signs • Acute changes in Mental Status/ Glasgow Coma Scale • Adjust antimicrobial therapy based on microbiologic findings

  40. Prophylactic Antibiotics (Slide 1 of 2) • Prophylaxis of close contacts should be started only after consultation with the local health department • Close Contacts • Members of same household • Individuals who share the same sleeping quarters • Day care contacts • Individuals exposed to oral secretions of infected patient

  41. Prophylactic Antibiotics (Slide 2 of 2) • Neisseria meningitidis • Close contacts • Rifampin 600 mg PO BID x 2 days • Ciprofloxacin 500 mg PO x1 dose • Ceftriaxone 250 mg IM x 1 dose • Azithromycin 500 mg PO x 1 dose • H. influenza • Close Contacts • Rifampin 600 mg PO BID x 4 days • Fully vaccinated children do not require prophylactic antibiotics

  42. Vaccination • Neisseria meningitidis • Meningococcal Polysaccharide Vaccine (Groups A / C / Y and W-135) • Meningococcal (Groups A / C / Y and W-135) Diphtheria Conjugate Vaccine • Meningococcal Group B vaccine • Streptococcus pneumoniae • Pneumococcal Conjugate Vaccines • 7-valent • 13-valent • Pneumococcal Polysaccharide Vaccine • 23-valent • H. influenza • Hib Conjugate vaccine

  43. Summary • Meningitis is an infection of the central nervous system with high rates of morbidity and mortality • Early identification of meningitis and early initiations of antibiotics is key to improve outcomes • High doses of antimicrobials that penetrate the CNS are required • Adjust therapy as soon as cultures finalized • Prevention with vaccination and prophylactic antibiotics

  44. References • Elshaboury RH, Hermsen ED, Holt JS, Mitropoulos IF, Rotschafer JC. Chapter 84. Central Nervous System Infections In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. • Tunkel AR, Hartman BJ, Kaplan SL, et.al.. 2004. Practice guidelines for the management of bacterial meningitis. Clin. Infect. Dis. 39:1267-1284. • Tunkel AR, Hasbun R, Bhimraj A, et.al.. 2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017; 64 (6): e34-e65.

More Related