EXAM 3 CNS Infections Dr. Cluck Flashcards by o e

Objectives

list common organism causing CNS infection

-appropriate drugs and formulations -> especially for ACUTE bacterial meningitis

-drugs for chemoprophylaxis
-who needs chemoprophylaxis and who doesn’t!

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What is the definition of meningitis?

inflammation of the membrane that covers the brain and the spinal cord, and the CSF that is in contact with that membrane

Bacterial meningitis is considered a medical emergency –> should be treated ASAP

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Gram-positive bacterial organisms causing CNS infections

Strep pneumonia (+)
Streptococcus agalactiae (+) (Group B strep) - 35% in neonates

Staph aureus (+)
Listeria monocytogenes (+)

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Gram-negative bacterial organisms causing CNS infections

Neisseria meningitis (-)
Haemophilus influenza (-)

Enterobacterales (-)

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Which organism causes the majority of CNS infections?

Strep pneuomonia (+)

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Which organism is known to cause CNS infections in neonates?

Streptococcus agalactiae (+) (Group B strep)
-also listeria and E.coli

-when seen in adults they often have other risk factors

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Which bacterial organisms are likely to be hospital-acquired?

Staph aureus (+)
Enterobacterales (-)

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Which bacterial organisms are likely to be community-acquired?

Strep pneumonia (+)
Streptococcus agalactiae (+)

Neisseria meningitis (-)
Haemophilus influenza (-)
Listeria monocytogenes (+)

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Which viral pathogens may cause CNS infection?

-Enteroviruses
-HIV
-HSV 1-> encephalitis
-HSV 2 -> meningitis

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Which other pathogens may cause CNS infection?

Fungal (Cryptococcal) -> patients often immunocompromised (fe AIDS with low CD4 count)

-Parasitic/Protozoal: Naegleria fowleri

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Which parasitic organism causes CNS infection?

Naegleria fowleri
-brain-eating ameba

often seen when people use Neti-pods with tap water (the water should be boiled)

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What are the general risk factors for CNS infections?

Immunosuppressive states
-HIV
-malingnancy (cancer)
-transplantations

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When to consider vaccination against encapsulated organisms?

in case of asplenia or splenectomy
-S. pneumo
-Haemophilus influenzae
-Neisseria meningiditis

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What are the risk factors for a S. pneumoniae CNS infection?

-Pneumococcal pneumonia
-sinusitis
-otitis media

-Alcoholism
-diabetes
-Asplenia/splenectomy
-Cochlear implants (ear, passage way to get into the CNS)

-S. pneumo bacteremia (S. pneumo in the blood)
-> consider Pneumococcal meningitis and treating with Ceftriaxone 2g IV q12h at least until meningitis is ruled out

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What are the risk factors for N. meningitis CNS infection?

-Complement deficiencies
-Nasopharyngeal carrier

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What are the risk factors for Group B streptococcus (S. agalactiae) CNS infection?

neonates

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What are the risk factors for L. monocytogenes CNS infection?

-neonates (< 1 month of age)
-pregnant women !!!
->60y of age (immunosenescence)

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What are the risk factors for H. influenzae CNS infection?

-Lack of vaccination !!!
-diabetes
-splenectomy
-chronic alcoholism
-multiple myeloma
-immund deficiency

What are the risk factors for Enteric gram-negative bacilli (hospital-acquired)?

chronic and debilitating diseases
-poorly controlled diabetes
-cirrhosis, alcoholism
-chronic UTI

neurosurgical procedures, particularly craniotomy
-> patient comes back with symptoms (febrile)
-> consider gram-negative Staph aureus, gram-negatives (but rare)

What are the risk factors for Strep pneumo?

-most common
-patients often with contiguous focus or foci (concomitant endocarditis, PNA, sinusitis)

-non-resistant stereotypes are more drug-resistant (what are the stereotypes?)

-> Ceftriaxone and Vancomycin

What are the risk factors for N. meningitis?

often in children in young adults (college age)
->patients living close promixity (dorms, base camps)

-Serotype B, C, and Y most often in US

Which vaccine protects against Serotype B N. meningitis?

Trumenba and Bexsero

What are the risk factors for Group B Strep ( Strep agalactiae)?

half of cases in the first month of life

adults may be affected by GBS meningitis, likely have risk factors

What are the risk factors for Listeria monocytogenes?

-use of TNF-alpha inhibitors (infliximab) - BIOLOGICS
-certain foods (cheese, deli meats, franks, cantaloupes!)
-pregnancy (200x greater risk)

Clinical Presentation of patients with meningitis

Fever strong headache altered mental status (AMS) nuchal rigidity (stiff neck) rash (not so often) -> presentation depends on patients age, etiology agent (organisms), immune status, area of brain that is involved

What is the gold standard for meningitis diagnosis?

Lumbar puncture (caution with increased cranial pressure) -> culture CSF -> PCR ->antimicrobial should not be delayed, given it too early may hinder diagnosis since it sterilizes the CSF within hours

When is the CSF indicative for a meningitis infection?

turbid or cloudy CSF fluid could be indicative of an infection -bloody: traumatic tap -other indicators: CRP, procalcitonin, CSF lactate -> not often used

Common CSF findings (not on exam?)

-elevated WBC >1000 per mm3 -predominance of PMNs (neutrophils) -low CSF to glucose ration

Which physical exams may be indicative of meningitis?

Brudzinski's sign Kernig's sign -> indicative of meningeal irritation if positive -LOW sensitivity

Which antimicrobials penetrate the CNS regardless of inflammation?

Sulfonamides Metronidazole (great when anaerobs are involved) Chloramphenicol Trimethoprim Rifampin Isoniazid -> they are usually not used, they use ß-lactams

Which antimicrobials penetrate the CNS with inflammation?

Penicillin G Ampicillin/sulbactam Ceftriaxone Cefuroxime Imipenem Meropenem Ciprofloxacin Levofloxacin Moxifloxacin (best penetration of the FQs) and more if there are newer drugs on the EXAM the answer is wrong, bc there is not enough data that supports sufficient CNS penetration

What are the antimicrobials of choice for meningitis?

Ceftraixone 2g q12h !!! Meropenem 2g q8h (needs dose adjustment in renal impairment)

Which drug may be used for Listeria?

Ampicillin/Gentamicin -> despite having low CNS penetration (data suggest lower mortality risk) -> could use Meropneme instead in case of allergy Meropenem alone covers all community acquired diseases Ceftriaxone/ampicillin

Which drugs have low CNS penetration?

Aminoglycosides 1st gen cephalosporin (cefazolin) -> use nafcillin instead 2nd gen cephalosporin Clindamycin Ketaconazole Itraconazol

How should CNS infection be treated empirically?

3rd/4th gen cephalosporin (ceftriaxone, ceftizidim, cefepime) + Vancomycin +/- rifampin Vancomycin: to cover penicillin-resistant Strep penumo or elevated MIC to cephalosporin Rifampin: not seen in praxis (due to DDIs) expert opinion add Aminoglycoside + Gent in patients who at risk for Listeriosis (homemade cheese, deli meats, elderly) -> de-escalate once culture and sensitivity come back

What is the duration of therapy?

7 days: (probably 10 d) N. meningitidis H. influenza 10-14 days: Strep pneumo 14-21 days- Strep agalactiae 21 days: Aerobic negatives Listeria (more than 21 days)

What is the role of Corticosteroids in CNS infection?

adjunct drug - Dexamethasone when used it should be given with the first dose of antimicrobials, bc some antimicrobials need inflammation for penetration

Treatment Aseptic meningitis

supportive care, self-limiting -initially the gram stain is negative, but still infectious -causing organism: enteroviruses, west-nil virus -drug-induced: (IV immunoglobulins (IVIG), NSAIDs TMP-SMX

Which organism may cause Aseptic meningitis?

-enteroviruses (most common 85%) -west-nil virus -Herpes simplex (HSV 1 and 2) -Spirochetes (T- palladium and B.burgdorferi) -Fungal - Cryptococcus neoformans and Coccidioides immitis -Tuberculous meningitis

Who needs meningitis prophylaxis?

-patients who are exposed to patients with confirmed N. meningitidis or H. influenza -Rule: >8h and <3ft

When is chemoprophylaxis not needed?

when exposed to patients with Strep penumo -> no data to support use of chemoprophylaxis

Meningitis prophylactic agents

-Ciprofloxacin 500 mg x1 dose (drug of choice) -Rifampin 600 mg q12h x4 doses (different dosing with H. influenza, often DDI with rifampin) -Ceftriaxone 250 mg IM x1 dose -Azithromycin 500 mg x1 dose (alternative) -> need prophylaxis regardless of immune state (also if they have been vaccinated)

Which organism causes Encephalitis?

inflammation of the brain parenchyma -caused by Herpesviruses (VZV, CMV, HHV-6) HSV-1 Arboviruses (West Nile Virus, St. Louis) Enteroviruses -HSV commonly affects the brain focally (on one area) -> personality changes, seizures, decreased level of consciousness