Bacterial Meningitis and Other CNS Infections

Objectives

• Identify the most common causes of bacterial meningitis in each patient population.

• Utilize diagnostic tests to determine the likely and definitive pathogens in bacterial meningitis

• Design an empiric pharmacotherapy regimen for bacterial meningitis taking into account:

  • Likely pathogens, antibiotic penetration, and dosing

• Based on culture and sensitivity data, refine antibiotic regimen for a patient with bacterial meningitis

• List advantages and disadvantages of each antimicrobial regimen in the treatment of bacterial meningitis

• Determine treatment options for viral encephalitis given laboratory diagnostic test results

What symptoms/labs suggest meningitis?

• Headache

• Stiff neck

• Elevated temperature (febrile)

• Increased serum WBC count (Neut dominant)

• Presence of ventriculostomy drain

Pathogens in Bacterial Meningitis by Age Group

Newborn-1 month

• S. agalactiae

• Gram negative enteric bacilli

• L. monocytogenes

1 month - 23 months

• H. influenza

• S. agalactiae

>50 years

• Gram negative enteric bacilli

• L. monocytogenes

**1 month - >50 years → everyone is susceptible to:

• S. pneumoniae

• N. meningitidis

What is criteria for neuroimaging?

• Age greater than 60

• History of CNS disease

• Immunocompromised state

• Recent seizure activity

• Altered consciousness/focal neurologic deficit

Patient Management

1. Identify likely organism based on patient presentation, age, and comorbid conditions

2. Perform lumbar puncture (LP) to collect CSF sample

3. Start empiric regimen to cover above pathogens

4. If LP delayed for neuroimaging, initiate empiric treatment within 3 hours of presentation

Empiric Antimicrobial Therapy - Drug

Empiric treatment + Dosing

Ceftriaxone → q12h at least

Vancomycin → 25mg/kg loading dose

Both are given because Ceftriaxone covers both pathogens. Vanco is added to make sure it is right the first time. penicillin and cephalosporin resistant.

Two advantages/characteristics of Ceftriaxone and Vancomycin

• Bactericidal

• Penetration into CSF

  • Molecular weight

  • Ionization

  • Lipid solubility

  • Protein binding

Bactericidal drugs

• Cell wall active agents

  • Beta lactams (rapidly bactericidal → cause apoptosis)

  • Vancomycin (slowly bactericidal)

• Aminoglycosides

• Fluoroquinolones

• Daptomycin

• Sulfamethoxazole/Trimethoprim

Bacteriostatic drugs

• Linezolid

• Tetracyclines

• Macrolides

Empiric Antimicrobial Therapy

Drugs with nontherapeutic levels in CSF (with or without inflammation)

• Aminoglycosides

• Early generation IV cephalosporins (1st and 2nd generation)

• All oral beta lactams

• Clindamycin

• Macrolides

• Beta lactamase inhibitors (pip-tazo)

Drugs with therapeutic CSF levels

• Penicillins

• ampicillin, penicillin G, nafcillin, piperacillin

• 3 rd/4th gen IV cephalosporins

• Fluoroquinolones

• Aztreonam

• Vancomycin

• Daptomycin

• Sulfonamides

From Cetriaxone + Vancomycin → If this patient had a documented prior allergy to PCN/Ceph (anaphylaxis) what alternative regimen would you recommend?

A. Aztreonam + vancomycin

B. Moxifloxacin + vancomycin

C. Gentamicin + vancomycin

D. Meropenem/vaborbactam + vancomycin

A. Aztreonam + vancomycin

Moxifloxacin is not favored

Aminoglycosides are given in addition to systemic IV

Beta-lactamase inhibitor too big.

What lab values indicate meningitis?

• Increased WBC count

• Increased protein

• Decreased glucose

Cerebrospinal Fluid Values

Definitive Antimicrobial Therapy

Assuming the patient is still on ceftriaxone and vancomycin, what changes would you make to the regimen?

A. Continue ceftriaxone monotherapy (discontinue vancomycin)

B. Continue vancomycin monotherapy (discontinue ceftriaxone)

C. Discontinue vancomycin and ceftriaxone and start meropenem

D. Discontinue ceftriaxone and vancomycin and start oral linezolid

A. Continue ceftriaxone monotherapy (discontinue vancomycin)

B → not wrong, beta lactam bactericial (vanco is not → ceftriaxone preferred)

C → Meropenem →not wrong but don’t need to use (we have a less borad spectrum)

D → not ideal Linezolid is bacteriostatic

Should any other medications be administered for meningitis?

Dexamethasone 0.15mg/kg iv q6h

• Administer 10-20 minutes prior to first dose of antibiotics → only for strep pnemno

How long should the patient receive treatment?

• Continue IV antibiotics for 10-14 days

• Continue dexamethasone for 2-4 days

What organisms would be suspected causes of infection in Healthcare-associated/acquired meningitis?

Post neurosurgery = nosocomial setting

Head/Trauma/Neurosurgery

• Aerobic gram neg bacilli including Pseudomonas aeruginosa

• Staphylococcus aureus

  • Including methicillin-resistant S. aureus (MRSA)

• Coagulase negative staphylococci

• Cutibacterium acnes

What empiric regimen would you start?

A. Amikacin 15mg/kg iv q24h + Vancomycin 15mg/kg iv q8-12h

B. Cefepime 2gm iv q8h + Vancomycin 15mg/kg iv q8-12h

C. Imipenem 1gm iv q8h + Vancomycin 15mg/kg iv q8-12h

D. Piperacillin/tazobactam 4.5gm iv q6h + Vancomycin 15mg/kg iv q8-12h

D → Pip-tazo (beta-lactamase inhibitor) not going to penetrate CSF (not going to site of infection).

A → Aminoglycosides don’t really penetrate

C → Seizure risk + does not penetrate CNS

B → Cefepime (has CNS side effects but will penetrate)

Cefepime 2gm iv q8h + Vancomycin 15mg/kg iv q8-12h

List two advantages of selected regimen

• Bactericidal

• Penetration into CSF

  • Check vanco troughs!

• Less risk of neurotoxicity

  • Avoid imipenem

What changes to the current regimen would you make → If culture comes back resistant to Cefepime

A. Continue cefepime and discontinue vancomycin B. Discontinue cefepime and vancomycin and change to meropenem

C. Discontinue cefepime and vancomycin and change to amikacin

B. Discontinue cefepime and vancomycin and change to meropenem

Amikacin cannot be given alone → Aminoglycoside has to be given with gram naegtive drug

Vanco not doing anything (not covering gram negative)

After 2 days of meropenem the repeat CSF cultures are still positive • Would you make any changes?

Could add intraventricular preservative-free tobramycin

Definitive Therapy

Acyclovir 10mg/kg IV

(interval based on crcl)

viral encephalitis symptoms

• Normal CSF glucose

• Increased CSF protein

• Lymphocyte increased

Summary acquired meningitis