U of M PHAR 6124 - Pathophysiology And Therapeutics Of Meningitis (59 pages)

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Pathophysiology And Therapeutics Of Meningitis



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Pathophysiology And Therapeutics Of Meningitis

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Pages:
59
School:
University of Minnesota- Twin Cities
Course:
Phar 6124 - Pharmacotherapy IV: Patient-Centered Pathophysiologic Approach
Unformatted text preview:

Pathophysiology And Therapeutics Of Meningitis Robert J Konop Pharm D Manager Clinical Formulary Development Pharmacotherapy Assessment Policy Prime Therapeutics Inc Objectives Identify the most common organisms for both viral and bacterial meningitis Understand the difference between viral and bacterial meningitis Know the composition of normal and abnormal CSF Objectives List the risk factors for CNS infections Describe the clinical presentation and laboratory results of characteristic meningitis Know both empiric and pathogen specific antibiotic regimens in meningitis Understand the recommended prophylactic regimens and their indications for use Definitions 1 Meningitis Inflammation of the meninges abnormal WBC in CSF 2 Septic versus Aseptic meningitis 3 Encephalitis Inflammation of the brain 4 Meningoencephalitis Inflammation of the brain accompanied by meningitis Meninges Dura Mater pachymeninges Directly beneath and is adherent to the skull Pia Mater Lies directly over the brain tissue Arachnoid The middle layer between the dura mater and the pia mater Subarachnoid Space Between the pia mater and the arachnoid Anatomy Physiology of the CNS Cerebrospinal Fluid Origin Infants 40 60ml Children 60 100ml Adults 110 160ml Viral Meningitis 1 Incidence 2 Clinical presentation Viral Meningitis Pathogens A Enteroviruses 85 B Mumps Virus 5 10 C Lymphocytic choriomeningitis virus D Herpes Simplex Virus HSV 2 Viral Meningitis Other Pathogens 10 adenoviruses poliovirus rhinoviruses influenza A B rotavirus CMV coronavirus Varicella Zoster virus Epstein Barr virus Enteroviruses Group A coxsackie 23 serotypes 14 of the cases Group B coxsackie 6 serotypes 12 of the cases Echoviruses 31 serotypes 75 of the cases Enteroviruses Respiratory Common cold Pharyngitis Pneumonia Gastrointestinal Vomiting Diarrhea Abdominal pain Eye Acute hemorrhagic conjunctivitis Heart Myopericarditis Skin Exanthem Neurologic Meningitis Enteroviruses Most common 85 95 of the cases Seasonal Late summer to fall Fecal to oral route Effects all age groups Typically 1 year old Mumps Virus Parotitis Meningitis occurs in 10 30 of the cases Encephalitis is rare Second most common viral meningitis 10 to 20 Peak late winter to early spring Humans only natural hosts Lymphocytic Choriomeningitis Virus Nonspecific prodrome Meningitis Chronic infection of the house mouse Infected rodent Common in the winter Herpes Simplex Virus HSV 2 Neonates during birth Sexually active adults Treatment Viral Meningitis SUPPORTIVE CARE Antibiotics until bacterial meningitis is ruled out Seizure control Symptom control Acyclovir Bacterial Meningitis Incidence 0 2 2 9 cases 100 000 year 1986 0 2 1 1 cases 100 000 year 1995 Very Young and Very Old Dramatic decrease in H flu Mortality Sequelae Incidence and Mortality Rate Organism of Total Cases Annual Incidence Fatality Rate H flu S pneumo N menin GBS L mono other 1986 45 18 14 5 7 3 2 15 1986 2 9 1 1 0 9 0 4 0 2 1 0 1995 7 47 25 12 8 1995 0 2 1 1 0 6 0 3 0 2 1986 3 19 13 12 22 18 1995 6 21 3 7 15 Bacterial Meningitis in the United States in 1995 NJM October 2 1997 337 14 970970 976 Bacterial Meningitis Most common organisms by population 0 4 weeks 4 12 weeks 3mo 4 yrs 5 9 yrs GBS E coli L monocytogenes other gram negatives GBS E coli L monocytogenes H influenzae S pneumoniae N meningitidis S pneumoniae H influenzae N meningitidis S pneumoniae H influenzae Bacterial Meningitis 9 18 years 18 60 years 60 years Neurosurg Closed Head Open Head N meningitidis S pneumoniae H influenzae S pneumoniae N meningitidis S pneumoniae N meningitidis L monocytogenes other gram negatives S aureus S epidermidis gram negatives S pneumoniae H influenzae S aureus gram negatives Pathogenesis Bacterial Invasion Parameningeal focus colonization Adhesions binding receptors pili Hematogenous spread Parameningeal seeding Colonization of hardware Direct inoculation Pathogenesis Bacterial elements inflammatory response Endotoxin Lipopolysaccharide Peptidoglycan Lipoteichoic acid Release of inflammatory mediators by astrocytes microglial endothelial cells TNF alpha IL 1 Pathophysiology Reduced cerebral perfusion secondary to edema Cerebral ischemia secondary to thrombosis Vasculitis Alteration of cerebral blood flow Direct neuronal cell damage secondary to bacterial elements activated leukocytes cytokines and other inflammatory mediators Pathophysiology Increased intracranial pressure Vasogenic edema cytokines act on endothelial cells to damage the BBB Cytotoxic edema direct damage to cells allowing buildup of intracellular water Interstitial edema obstruction of CSF flow and removal Brain herniation Risk Factors 1 Respiratory tract infection 2 Otitis media 3 Mastoiditis 4 Head trauma 5 Splenectomy 6 Sickle cell disease 7 Immunosuppressive therapy 8 Immunocompromised host 9 Alcoholic patients 10 Patients with hardware shunts etc Clinical Presentation Physical signs symptoms Fever Headache Photophobia Nausea vomiting Mental status changes Stiff neck back Positive Brudzinski s sign Positive Kernig s sign Deafness Seizures Focal neurologic deficit Hydrocephalus Laboratory Studies Lumbar Puncture CSF cell count CSF chemistries CSF gram stain CSF culture Blood Culture Sputum Culture Urine Culture Peripheral CBC and Electrolytes Clinical Presentation and Diagnosis Abnormal CSF findings by type of meningitis Type WBC mm2 NML 10 Bact 400 100 000 Viral 5 500 Fungal 40 400 T B 100 1 000 Diff 50 lymphs 90 PMN s 50 lymphs 50 lymphs 50 lymphs Protein mg L 50 80 500 30 150 40 150 40 400 Glucose mg dL 30 70 35 NML low NML low NML low Clinical Presentation and Diagnosis Bacterial antigen detection tests 69 accurate when positive cultures Useful when antibiotics were given before the CSF culture was taken May react to other organisms Other tests Counterimmunoelectrophoresis CIE and latex fixation encapsulated organisms Limulus lysate assay gram negative endotoxin Common Bacterial Organisms Haemophilus influenzae Peak incidence 6 12 months of age declines after 24 months of age Deafness 6 Coma seizures common Close contacts are 200 1000 x risk Resistance pattern is growing throughout the U S Dramatic decrease in cases since 1990 Common Bacterial Organisms Neisseria meningitidis Usually occurs winter spring Five main serogroups A B C Y and W 135 A and C epidemics B individual cases Y pneumonia May present with a characteristic immune reaction 10 14 days after infection fever arthritis pericarditis Rx with NSAID s Common Bacterial Organisms


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