Meningitis Hai Ho, MD Department of Family Practice Riverside County Regional Medical Center

Easy Concept Treat empirically with medications that kill the organisms involved Therefore, if you know the organisms involved, you could choose the right medications

Organisms involved Bacteria Bacteria Viruses Viruses Fungi Fungi Parasites Parasites

The most common organisms involved in meningitis? Depend on the age and the clinical situations

Neonates to 2 months of age 4,7 ? VirusesViruses Herpes SimplexHerpes Simplex EnterovirusesEnteroviruses Cytomegalovirus (CMV)Cytomegalovirus (CMV) BacteriaBacteria Group B StreptococcusGroup B Streptococcus Escherichia ColiEscherichia Coli Listeria monocytogenesListeria monocytogenes

Listeria monocytogenes 4,5 Risk groups Risk groups –Extreme age –Impaired immunity –Pregnancy Presentations Presentations –Subacute –Ataxia and myoclonic seizure – small abscesses in cerebellum and brainstem Treatment – aminoglycoside (poor CSF penetration) synergistic with ampicillin Treatment – aminoglycoside (poor CSF penetration) synergistic with ampicillin

Antibiotics for infants 0 to 2 months of age? Third-generation cephalosporins (cefotaxime or ceftriaxone) Ampicillin

Should corticosteroid be used in meningitis 4 ? Controversial Controversial Reduce deafness in children with H. influenza Reduce deafness in children with H. influenza Give before or at the time of initiation of antibiotics x 2 to 4 days Give before or at the time of initiation of antibiotics x 2 to 4 days Lack evidences of beneficial effects in adults Lack evidences of beneficial effects in adults

Greater than 3 months to 60 years of age? Streptococcus pneumoniae Neisseria meningitidis

Antibiotics for patients greater than 2 months to 60 years of age? Third-generation cephalosporins (cefotaxime or ceftriaxone) Vancomycin

Vancomycin 4,5 Not to use as monotherapy because of its poor CSF penetration Not to use as monotherapy because of its poor CSF penetration Added to cover resistant pneumococci Added to cover resistant pneumococci If corticosteroid is used, need to add rifampin because corticosteroid decrease CSF penetration of vancomycin If corticosteroid is used, need to add rifampin because corticosteroid decrease CSF penetration of vancomycin

Greater 60 years of age Streptococcus pneumoniae Neisseria meningitidis Listeria monocytogenes

Antibiotics for patients greater than 60 years of age? Third-generation cephalosporins (cefotaxime or ceftriaxone) VancomycinAmpicillin

Nosocomial meningitis Most cases from neurosurgical procedures or CSF shunt placement Most cases from neurosurgical procedures or CSF shunt placement Common bacteria Common bacteria –Gram negative rods: E. Coli, Klebsiella, pseudomonas, Acinotobacter, Enterobacter, Serratia species –Staphylococci: Staphylococcus aureus, staphylococcus epidermidis

Antibiotics for nosocomial meningitis 4,5 Ceftazidime or cefepime and Vancomycin Ceftazidime or cefepime and Vancomycin Imipenem Imipenem –Resistant Gram negative rods –Associated with seizure Aminoglycoside Aminoglycoside –Indicated in patients with poor response to IV antibiotics –Intrathecal

Aseptic meningitis 8 CSF analysis not consistent with bacterial infection

Infectious aseptic meningitis 9,10 ? Viruses Viruses Bacteria – mycobacterium tuberculosis, treponema pallidum, borerrelia burgdorferi Bacteria – mycobacterium tuberculosis, treponema pallidum, borerrelia burgdorferi Fungi – cryptococcus neoforman, coccidioides immitis, histoplama capsulatum Fungi – cryptococcus neoforman, coccidioides immitis, histoplama capsulatum Parasites Parasites

Non-infectious aseptic meningitis? Drugs Drugs –Penicillin –Trimethoprim/sulfamethoxazole –NSAIDs –Carbamezepine Granuloma Granuloma Neoplasm Neoplasm Idiopathic Idiopathic

Treatment for aseptic meningitis? Viral causes Viral causes –Mainly supportive care –Enterovirus »Most common »Diverse group of RNA viruses including coxsackieviruses, echoviruses, and polioviruses –HIV – anti-HIV meds, but most resolve spontaneously –Herpes simplex – acyclovir –CMV – ganciclovir (not approved for CNS) Syphilis – Penicillin G Syphilis – Penicillin G Fungi – amphotericin Fungi – amphotericin Tuberculosis – Isoniazid, pyazinamide, rifampin, steptomycicin, ethambutol Tuberculosis – Isoniazid, pyazinamide, rifampin, steptomycicin, ethambutol

Clinical presentations in children? Nonspecific General toxic appearance Fever Decreased PO intake Decreased alertness

Clinical presentations in adults? Classic triad Classic triad –Fever, neck stiffness, and altered mental status –Fever is the most sensitive, followed by neck stiffness –Mental status »High sensitivity – normal rules out meningitis in low-risk patients »More common in bacterial than viral meningitis Kernig and Brudzinski - Low sensitivity but high specificity Kernig and Brudzinski - Low sensitivity but high specificity Jolt accentuation of headache – negative test excludes meningitis Jolt accentuation of headache – negative test excludes meningitis

Diagnostic tests 4,5 ? Lumbar puncture Lumbar puncture Head CT prior to lumbar puncture Head CT prior to lumbar puncture –Should NOT delay treatment – blood culture and antibiotics –Indicated if patients have altered mental status, focal neurological deficits, and signs of intracranial pressure such as papilledema

CSF analysis Components Normal Newborn Normal Children Bacterial Meningitis Viral Meningitis Herpes Meningitis Glucose (mg/dL) <30>30>30 Protein (mg/dL) > >75 Leukocytes/  L >1, ,000 Neutrophils (%) 2-30>50<40<50 Erythrocytes/  L True CSF WBC = Measured CSF WBC x (1 – CSF RBC  blood RBC) In bloody tap, if WBC/RBC in CSF < that of blood

Bacterial invasion of CNS Ventriculitis CSF flow resistance Increased ICP Leptomengitis IL1 & TNF production Endothelial injury Increased blood brain barrier permeability Cerebral edema Increased CSF protein Vascular thrombosis Decreased blood flow Cerebral hypoxia Glycolysis Decreased CSF glucose Increased CSF lactate Infarction Seizure Abscesses

CSF analysis Bacterial antigens by counterimmunoelectrophesis and latex agglutination – helpful when patients are already on antibiotics Bacterial antigens by counterimmunoelectrophesis and latex agglutination – helpful when patients are already on antibiotics Culture Culture PCR for viruses and tuberculosis PCR for viruses and tuberculosis VDRL VDRL

Repeat CSF analysis 4 ? Consider in all infants and children with bacterial meningitis – hours after treatment Consider in all infants and children with bacterial meningitis – hours after treatment Adults Adults –Penicillin-resistant pneumococci or Gram negative rod –Poor clinical response

Complications of meningitis? Seizure Seizure Subdural effusion Subdural effusion –20-30% of infants with meningitis –Commonly with H. influenza type b & pneumococcal meningitis –Drain only with neurological symptoms from mass effect Subdural empyema – drainage & prolonged antibiotics Subdural empyema – drainage & prolonged antibiotics Hearing loss Hearing loss SIADH – very cautious with fluid restriction because cerebral vascular autoregulation is compromised in meningitis SIADH – very cautious with fluid restriction because cerebral vascular autoregulation is compromised in meningitis Loss of cognitive functions Loss of cognitive functions

Prevention of meningitis 4 Vaccines Vaccines –H. influenzae in children Chemoprophylaxis Chemoprophylaxis –Rifampin x 4 days –Neisseria meningitidis »Index case to eradicate pharyngeal carriage »Members in same household »Prolonged close contacts »Direct exposure to respiratory secretion (suction, intubation) –Haemophilus influenzae type b »Children <4 years of age with close contact »All household members with children < 4 years of age

References 1. Smith AL. Bacterial Meningitis. Pediatrics in Review 1993;14: Attia J, et al. Does This Adult Patients Have Acute Meningitis? 3. Uchihara T, Tsukagoshi H. Jolt Accentuation of Headache: the Most Sensitive Sign of CSF Pleocytosis. Headache 1991; 31: Thomas F. Prevention and Treatment of Bacterial Meningitis Mathisen GE. Bacterial Meningitis: 11 Questions Physicians Often Ask. Consultant Wubbel L, McCracken GH. Management of Bacterial Meningitis: Pediatrics in Review 1998;19: Prober CG. Central Nervous System Infections. In: Behrman ER, ed. Textbook of Pediatrics. Philadelphia: W.B Saunders Company; 2000: Ryan ME, Brendlinger J, Scott T, Metrishyn L. Aseptic Meningitis. Cortlandt Forum 2000.