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Pharmacology of Encephalitis/Bacterial Meningitis Cheat Sheet by

Pharmacology of Encephalitis and Bacterial Meningitis.

Pathop­hys­iology

Meningitis
Inflection and inflam­mation of the meninges.
Enceph­alitis
Infection and inflam­mation of the brain or spinal cord parenchyma itself.
Common causes:
Viruses, Bacteria, Fungi, and Parasites
 
Viral enceph­alitis is the most common type of enceph­alitis, but less severe than bacterial.

Enceph­alitis

Common Viruses
Herpes Simplex (most common, >42%)
 
Varicella Zoster Virus
 
Epstein Barr Virus
Diagno­stics
Lumbar puncture- CSF
 
PCR for the identi­fic­ation of viruses (HSV, EBV, CMV, HHV6, and entero­vir­uses)
 
*The same organisms respon­sible for viral meningitis usually are also respon­sible for enceph­alitis.
Diagnostic Criteria for Enceph­alitis
Major Criterion
Required
 
Subacute onset of impairment in the domains of consci­ous­ness, memory, mental status, or new onset psychi­atric changes without altern­ative cause.
Minor Criterion
( at least 2)
 
Fever >/= 100.4 F within the 72 hours before or after presen­tation
 
Seizures not attributed to a previous seizure disorder.
 
Cerebr­ospinal fluid pleocy­tosis (WBC > 5/cubic mm)
 
Evidence of brain parenc­hymal inflam­mation on neuroi­maging (acute or subacute)

Symptoms of Meningitis

Early Symptoms
Headache
 
Fever
 
Nausea
 
Vomiting
Later Symptoms
Drowsiness
 
Confusion
 
Stiff ness and pain on flexion of the neck (Nuchal Rigidity)
 
Seizures
 
Non-bl­anching purpuric rash (Menin­goc­occal)
 
Photop­hobia
 
Rapid Breathing Rate
Triad
Headache
 
Fever
 
Nuchal Rigidity

Mening­ococcal Meningitis

Mening­ococcal meningitis is a bacterial form of mening­itis, a serious infection of the thin lining that surrounds the brain and spinal cord.
This is the most important pathogen for meningitis (Neisseria Mening­itides) because it has the potential to cause epidemics.
Charac­terized by non-bl­anching purpura.
You can easily tell it by pushing a glass against it and if it disappears it is not mening­itis.

Mening­ococcal Meningitis

Mening­ococcal meningitis is a bacterial form of mening­itis, a serious infection of the thin lining that surrounds the brain and spinal cord.
This is the most important pathogen for meningitis (Neisseria Mening­itides) because it has the potential to cause epidemics.
Charac­terized by non-bl­anching purpura.
You can easily tell it by pushing a glass against it and if it disappears it is not mening­itis.

Types of Antibi­otics vs. Age

Is Meningitis Contag­ious?

Parasitic
non contagious
Fungal
non contagious
Viral
contagious
Bacterial
contagious
 

General Notes on CNS Infections

Acute infections such as bacterial and viral meningitis and enceph­alitis require quick distin­gui­shing and treatment.
It is imperative to differ­entiate between them, identify the pathogen, and quickly initiate therapy.
Neisseria, Haemop­hilus, Hepes simplex 1, Varicella Zoster

Symptoms of Enceph­alitis

Deep cognitive functions disturbed.
Confusion or disori­ent­ation.
Seizures or fits.
Changes in person­ality and behavior.
Difficulty speaking.
Weakness or loss of movement in some parts of the body.
Loss of consci­ous­ness.

Diagno­stics to Confirm Meningitis

CT- to rule out bleeds
Head Scans
Lumbar Puncture (Gold Standard) confirms diagnosis. This is CI in mening­ococcal septic­emia, so you need to do blood cultures and PCR, instead. CI if there is bulging of the fontanells in an infant (this indicates increased ICP), CI in hydroc­eph­alus.
PCR- determines viral etiology
Blood Culture

Empiric Treatment

Preterm to <1 Month old
Ampici­lli­n+C­efo­taxime
1-3 Months old
Ampici­llin+ Cefotaxime or Ceftri­axone
>3 months to adults <50
Ceftri­axone or Cefota­xime+ Vancom­ycin+ Dexame­thasone (steroid for ICP)
Adults with >55 or with alcoholism or disease
worried about listeria so + ampicillin (Ampic­illin +Ceftr­iaxone or Cefotaxime + Vancomycin + Dexame­tha­sone)
Altern­atives for penicillin allergy
Can substitute TMP-SMP (Bactrim) or meropenem for Ampicillin if you need the possible listeria coverage in immuno­sup­pressed or >50 yo
 
Meropenem can also be substi­tuted in for ceph if can't take ceph. Aztreonam is also an option.
Dexame­thasone
Given 10-20 minutes before antibiotic therapy and continue for 2-4 days
 
Shown to decrease morbidity and mortality by decrease inflam­matory response secondary to bacterial lysis which usually causes detrim­ental physio­logic effects- used for s. pneumo or haemop­hilus causes only, not shown to benefit with other pathogens.
 
No benefit if given after antibi­otics are initiated.
 
Given IV 10mg (0.15 mg/kg ped) Q6hrs for up to 4 days

Bacterial Meningitis Treatment

If the lumbar puncture is delayed for any reason, including the need for additional diagnostic testing, such as a CT scan of the head- then empiric antibiotic therapy should be started as soon as possible, ideally after blood cultures have been performed.
It is important to start antibiotic therapy even if the evaluation for bacterial meningitis is ongoing, since as delay in treatment is associated with increased morbidity and mortality. Recomm­ended empiric treatment of bacterial meningitis is based on a patient's age and comorbid condit­ions.

Vancomycin

MOA:
Inhibits peptid­oglycan cross linking, leading to weaker cell membrane
Indica­tions:
Primarily activity is against gram positive (too large to penetrate through gram negative cell membranes)
Formul­ations:
Admini­stered via IV infusion (oral is only given for the treatment of colitis caused by cdiff)
ADRs
Fairly frequent. Irritating to tissues, chills, fever, nephro­tox­icity is common, rare ototox­icity red man syndrome (infusion flushing caused by the release of histamine can prevent this by admini­stering slowly, or pretre­ating with antihi­sta­mines )
Notes
Widely distri­buted into tissues, including adipose, but poorly absorbed from GI tract
 
Therap­eutic drug monitoring protocols of vancomycin are put in place to measure AUC levels in order to minimize occurrence of nephro­tox­icity. Calcul­ating AUC is used to check for therap­eutic levels and to monitor for toxicity. Accumu­lates in renal therapy.
 
Treats MRSA
 
Works synerg­ist­ically with gentamicin and other aminog­lyc­osides for treating entero­cocci.
 
VRE (vanco­mycin resistant entero­cocci) are becoming more prevalent.
 

Meningitis vs. Enceph­alitis

Treatment of Enceph­alitis

Start IV Acyclovir (for herpes simplex) while awaiting CSF results. This is the empiric therapy of choice.
Herpes Simplex is the most common cause of enceph­alitis so starting acyclovir will help to prevent death or serious outcomes.
Pediatrics and Adults: acyclovir 10mg/kg IV q8h
Acyclovir is used to prevent and treat herpes infection of the skin, mouth, and mucous membranes; herpes zoster (shing­les); chicken pox; and genital herpes.

CFS Analysis

Bacterial
Viral
Cloudy
Clear (Usually)
Glucose is low (bacteria is using the glucose)
60-80% of normal plasma levels
Proteins are high
Normal protein levels
WBC- Neutro­phils, PMNs
Lympho­cytes

Bacterial Meningitis Causes

0-6mos
6mos-6yrs
6yrs-60yrs
60+
Group B Strep
S. Pneumoniae
S. Pneumoniae
S. Peneum­oniae
E. Coli
N. Meningitis
N. Meningitis
Gram Negative Rods
Listeria
Entero­virus
HSV-1
Listeria
 
H. Influenza
Entero­virus

Causes Notes

Usually caused by strep pneumoniae and Neisseria meningitis in those 2-50 yo
Listeria monocy­togenes should be considered in pregnancy, >50, alcoho­lics, and immuno­com­pro­mised patients.

Bacteria Meningitis Causes and Treatments

Medica­tions and the CSF

The CSF is hard for a lot of medica­tions to penetrate due to the BBB. To overcome this you can increase the dose or depend on the inflam­mation to open up permea­bility.
Most medica­tions do not penetrate into the uninflamed meninges, however in meningitis a lot of antibi­otics are able to gain higher concen­tra­tions in the CSF because the inflam­matory response allows the BBB to be more penetrable to hydrop­hilic substances (we already know lipophilic drugs have are more permeable)
Ex. Hydrop­hilic antibi­otics are beta lactams and vancom­ycin.
Beta lactams have the most evidence behind them in meningitis prophy­laxis due to their ability to eradicate the causative pathogens, BUT dosing has to be increased in order to gain approp­riate concen­tra­tions in the CSF.
Of the cephal­osp­orins cefotaxime and ceftri­axone are the most used.

Prophy­laxis for Meningitis

Haemop­hilus Influenza B
Rifampin for 4 days for both peds and adults
 
recomm­ended for all household contacts with kids <4 that haven't been fully vaccin­ated, child care settings when 2 or more chases have occurred within 60 days.
Neisseria Mening­itidis
Rifampin (2 days)
 
Ciprof­loxacin (adults only) (BS)
 
Ceftri­axone (IM 1 dose)
 
start withing 24 hours after identi­fied, should involve household members, child care contacts, direct exposure to oral secret­ions. After 14 days no prophy­laxis is recomm­ended.
Report all cases to the CDC
 

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  • Published: 19th May, 2023

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