CNS INFECTIONS MENINGITIS

CNS INFECTIONS MENINGITIS Learning Objectives: 1. Describe patient risk factors,signs and symptoms that may indicate meningitis 2. Identify tests and significant laboratory values used to diagnose meningitis 3. List common causative organisms for meningitis 4. Distinguish between antimicrobial treatment options for meningitis based on causative organisms 5. Describe supportive care and prophylactic treatment that may be required for meningitis Patient Case: Chief Complaint: From mom - Why is my baby so sleepy? And what is this purple rash? HPI: David St. Hubbins is a 2 yo, 13.6 kg male toddler who presented to the emergency department with his mother. Mom reports that she noticed him sleeping longer than normal since yesterday evening after returning from daycare, as well as this morning. She also reports that he had a poorer than normal appetite at dinner and breakfast. She also notes the rapid appearance of a purplish rash on his extremities, trunk, and back. At 08:00 she checked his temperature, reporting a temperature of 39.1 C. At this point, the mother reports that she called her sister who is a nurse, and was told to go straight to the emergency room. When aroused prior to transport, David was irritable and frequently crying. She indicates that during transport, David was in and out of sleep and did not respond well to normal stimuli. There was one episode of slight vomiting during transit. Meds: None; immunizations up to date per the U.S. CDC Advisory Committee for Immunization Practices (ACIP) PMH: David was born via an uncomplicated vaginal delivery at 39 weeks. Mother reports one episode of otitis media at 13 months of age, treated with amoxicillin. FH: Mother is in good health; father has hypercholesterolemia; maternal grandparents both with metabolic syndrome; paternal grandfather in good health; maternal grandmother alive, history of breast cancer. SH:Lives with mother and father. Father is a rock musician and mother is a teacher. David began attending daycare 3 months ago. Father is a smoker. No pets in the home. Background Inflammation of the meninges (membranes) surrounding the brain and the spinal cord Neurological complications Seizures Hearing loss Hydrocephalus (CSF within ventricles of brain) Categories of Meningitis Hospital or community acquired Acute (hours-days) or chronic (weeks-months) Bacterial, viral, fungal Bacterial is most common, fungal is least common

Pathophysiology Entry into host Nasopharyngeal colonization leading to phagocytosis into bloodstream (most common) Host inflammatory response triggered by phagocytosis of organism Causes alteration of BBB Ultimately leads to increased cranial pressure, cerebral edema, CSF pleocytosis, decreased cerebral blood flow, cerebral ischemia, and death Direct inoculation ( trauma, CSF catheter) & parameningeal focus (middle ear infection, paranasal sinus infection) possible Risk factors - most common Bacterial Passive or active cigarette smoke exposure Children with cochlear implants with a positioner Signs/Symptoms Fever/chills Vomiting Photophobia Severe headache Rash (not always) Meningismus Neck rigidity Brudzinski s or Kernig s sign (less common in children) Altered mental status (lethargy, coma, drowsy) Seizures Sepsis (low BP, high HR, poor peripheral perfusion) Shock N. meningitidis Neonates/infants: fever, poor feeding, irritability only Petechiae N. meningitidis Septic emboli Back to our case: What are the symptoms of meningitis in this patient? Gen: Lethargic toddler with generalized rash in mild-moderate distress VS: SBP 75, HR 152, RR 48, T 39.4 C; Wt 13.6 kg, SatO2 (RA): 98% HEENT: PERRLA, tympanic membranes erythematous bilaterally Chest: Lungs clear bilaterally CV: Sinus tachycardia, regular rhythm, no murmurs, rubs, gallops Abd: Soft, distended, (+) BS, (+) purpuric rash Extremities: Capillary refill 4 seconds, extremities mottled and cool to the touch; (+)mildly blanching, purpuric rash is present; petechial lesions noted

Neuro: Listless; arousable to strong stimuli only, ( ) Brudzinski s, ( ) Kernig s, (+) Babinski Testing/Diagnosis for Meningitis Lumbar Puncture for CSF (adult) Marker Normal Bacterial Viral Fungal TB WBC (cells/mm 3 ) <5 1,000-5,000 100-1,000 40-400 100-500 Differential (%) >90 monocytes > or = 80 PMNs 50 lymphs, PMNs >50 lymphs >80 lymphs, PMNs Protein (mg/dl) <50 100-500 30-150 40-150 < or = 40-150 Glucose (mg/dl) 50 (66%) <40 <30-70 <30-70 <30-70 CSF and gram stain are most important for bacterial Gram stain rapid and sensitive if done before antibiotic therapy PCR, latex agglutination and enzyme immunoassays also done Back to our case: What lab values indicate meningitis in our patient? How do you know if this bacterial/viral/or fungal? CSF analysis: Color/appearance: straw/cloudy, glucose 38 mg/dl, protein 315 mg/dl, WBC 420/mm3 (2% lymphocytes, 2% monocytes, 96% neutrophils), RBC 500/mm3 Chest X-Ray: No acute cardiopulmonary process noted Causal Organisms Bacterial By age < 1 month S. agalactiae, E. coli, Listeria, Klebsiella 1-23 months S. pneumoniae, N. meningitidis, S. agalactiae, H. influenzae, E. coli 2-50 years N. meningitidis, S. pneumoniae > 50 year S. pneumoniae, N. meningitidis, Listeria, aerobic gram-negative bacilli *Newborns, 50+, newborns -1 month at risk for Listeria

** Haemophilus Influenzae less common now due to Hib vaccine Viral Herpes Simplex Most treatable Influenza Epstein Barr Varicella West Nile Fungal Cryptococcus neoformans, gattii Back to our case: What are the most common causative organisms in our patient based on the information below and patient characteristics? CSF serology/urine antigen testing: Haemophilus influenzae type B ( ); Streptococcus pneumoniae ( ); group B Streptococcus ( ) CSF Gram stain: Gram-negative diplococci Cultures: Blood, Urine, and CSF cultures: Pending Treatment Options - Bacterial Considerations Needs to distribute to CSF! Lipophilic > hydrophilic Consider the inflammation in meninges - increases drug penetration Use maximum doses to reach CNS IV route needed Use bactericidal agents

Drugs and their relative CNS penetration Empiric antibiotic regimens (before organism is known) Do NOT delay empiric antibiotics, even if delaying lumbar puncture Continue for at least 48-72 hours or until meningitis can be ruled out

Back to the case: What empiric antibiotic regimen(s) would be appropriate for this patient based on patient factors and most likely causative organism? CSF serology/urine antigen testing: Haemophilus influenzae type B ( ); Streptococcus pneumoniae ( ); group B Streptococcus ( ) CSF Gram stain: Gram-negative diplococci Cultures: Blood, Urine, and CSF cultures: Pending Definitive therapy (once organism is identified) Duration of therapy N. meningitidis 7 days H. influenzae 7 days S. pneumoniae 10 to 14 days Aerobic gram-negative rods 21 days Listeria monocytogenes at least 21 days Adjunctive Therapy Steroids- Dexamethasone Recommended for children six weeks or older with H. influenzae meningitis or adults with S. pneumoniae meningitis Dosed 0.15 mg/kg IV every 6 hours for 2 to 4 days, initiated 10 to 20 minutes before/with but NOT after 1st dose of abx Watch GI bleeds and hyperglycemia Use is controversial due to decreased antibiotic penetration into CSF Does not seem to affect vancomycin and ceftriaxone Antipyretics/analgesics

IV fluids Immunizations Hib Meningococcal Pneumococcal Seasonal influenza H1N1 Prophylactic antibiotics for close-contacts ** Close contact = at least 4 hours/day with infected patient for 5 out of 7 days before treatment was started** H. influenzae - for close contacts that are unimmunized children; only after reporting to local health department and CDC Rifampin 20 mg/kg/day (600 mg max) once/day x4 days if not vaccinated Due to high risk of secondary cases w/in 30 days of contact N. meningitidis - for any close contact (regardless of vaccination status) Rifampin Adults 10 mg/kg/dose (600 mg max) x4 doses Children over 1 month 10 mg/kg BID Children under 1 month 5 mg/kg BID Ceftriaxone 125 mg (under 12) or 250 mg (over 12) IM x1 dose Ciprofloxacin 500 mg PO x1 dose (over 12) S. pneumoniae None Viral Meningoencephalitis rare, but toxic and merits treatment Empiric Therapy - initiate as soon as possible if suspected encephalitis Acyclovir 10 mg/kg IV every 8 hours in children/adults with normal renal function 20 mg/kg IV every 8 hours in neonates No specific treatment If signs of rickettsial or ehrlichila infection add doxycycline Definitive therapy See Dipiro Chapter 106 See Mcgill F, Heyderman RS, Michael BD, et al. Corrigendum to "The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent Adults" [J Infect 72 (2016) 405-438]. J Infect. 2016;72(6):768-769. Fungal - Most rare! See Dipiro Chapter 106 and Dipiro Handbook Chapter 38

Monitoring Signs of fever, headache, meningismus (nuchal rigidity, Brudzinski s or Kernig s sign), blood pressure, heart rate, respiratory rate, and signs of cerebral dysfunction every 4 hours for 3 days, then daily Glasgow Coma Scale in critically ill patients Repeat lumbar puncture Indicated for: Patients who do not clinically respond to appropriate antibiotics after 48 hours Neonates with gram negative bacilli (because treatment duration depends on results) Protein, glucose, WBC count and differential References: - Link to CDC Meningitis Guidelines - https://www.cdc.gov/meningitis/viral.html - Link to IDSA Meningitis Guidelines - http://www.idsociety.org/guidelines/patient_care/idsa_practice_guidelines/infections_ by_organ_system/central_nervous_system_(cns)/bacterial_meningitis/ - Link to Dipiro Textbook- Chapter 36 - https://accesspharmacy.mhmedical.com/content.aspx?bookid=2177&sectionid=1654728 51 - Link to Dipiro Handbook - Chapter 36 - http://accesspharmacy.mhmedical.com/content.aspx?bookid=2177&sectionid=16547285 1 - Fungal Infections, Invasive. In: Wells BG, DiPiro JT, Schwinghammer TL, DiPiro CV. eds. Pharmacotherapy Quick Guide New York, NY: McGraw-Hill;. http://accesspharmacy.mhmedical.com/content.aspx?bookid=2177&sectionid=165472919. Accessed January 30, 2018. - Mcgill F, Heyderman RS, Michael BD, et al. Corrigendum to "The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent Adults" [J Infect 72 (2016) 405-438]. J Infect. 2016;72(6):768-769.