Bacterial Meningitis

What is Bacterial Meningitis?

- Inflammation of the meninges (area between brain and skull), caused by a bacteria.
- Bacteria gets into the CSF
o Which has bad defense mechanisms
- Presentations:
o Headache, fever, rigidity, delirium
- Risk factors:
o Bacteremia
o Endocarditis
▪ Prolonged infection
o Surgery or trauma
o Immunocompromised

Characteristics of CSF that point to bacterial meningitis

1. Glucose concentration ____________

2. CSF to serum glucose ratio of ____________
3. Protein concentration ____________
4. WBC count above ____________
a. With presentation of neutrophils usually greater than 80%

**If missing one of these, cannot rule out!

Better prediction with >99% certainty: WHEN 1 WAS PRESENT!

1. CSF glucose below ____________

2. Protein concentration above ____________
3. WBC count above ____________
4. Neutrophil count more than ____________

Initial Management:

1. When bacterial meningitis is suspected:

a. Blood sample
i. Often positive
b. Lumbar puncture
i. Everyone!
ii. Unless: ______________ or ______________
1. →Then order a CT before the lumbar puncture
How do we decide empiric therapy?

- Age and conditions!

- So for initial therapy, we assume resistance is likely because it is a high mortality disease!
- Empiric therapy is started in:
o Purulent meningitis with negative CSF gram stain
o Lumbar puncture is delayed

Should we use oral or IV therapy?

Age:

1. < 1 month
a. Common pathogens
i. Streptococcus agalactiae
ii. E. Coli
iii. Listeria monocytogenes
iv. Klebsiella species
b. Therapy
i. Ampicillin + 3rd generation Cephalosporin
ii. Ampicillin + AMG
2. 1-23 months
a. Common pathogens
i. Streptococcus pneumonia
ii. Neisseria Meningitidis
iii. Strepococcus agalaciae
iv. Haemophilus influenzae
v. E. Coli
b. Therapy
i. Vancomycin + 3rd generation cephalosporin
3. 2-50 years old
a. Common pathogens
i. N. Meningitidis
ii. Streptococcus pneumonia
b. Therapy
i. Vancomycin + 3rd generation cephalosporin
4. >50 years old
a. Common pathogens
i. Streptococcus pneumonia
ii. Neisseria meningitdis
iii. Listeria monocytogenes
iv. Gram-negative bacilli
b. Therapy
i. Vancomycin + Ampicillin + 3rd generation cephalosporin
 Strep. Neisseria Listeria Streptococcus Haemophilus E. coli
pneumoniae meningitidis monocytogenes agalactiae influenzae
Recommended Vancomycin + 3rd generation Ampicillin or Ampicillin or 3rd generation 3rd generation
Therapy 3rd generation cephalosporin PCN G PCN G cephalosporin cephalosporin
cephalosporin

Alternative Meropenem, PCN G, TMP/SMX, 3rd generation Chloramphenicol, Cefepime,

Fluroquinolone ampicillin, meropenem cephalosporin cefepime, meropenem,
chloramphenicol, meropenem, aztreonam,
fluoroquinolone, fluoroquinolone fluoroquinolone,
aztreonam TMP/SMX

Based on isolated pathogen, how do we determine antimicrobial therapy?

1. Susceptibilities!
2. As always we want to direct therapy as much as possible. So depending on the bacteria and
susceptibilities we direct our therapy!
a. Streptococcus pneumoniae
i. We look at PCN MIC

PCN MIC (mcg/ml) Therapy Alternative

< 0.1 PCN G or Ampicillin 3rd Generation
Cephalosporin,
Cefepime, Meropenem
0.1 – 1 3rd Generation Fluoroquinolone
Cephalosporin
>2 Vancomycin + 3rd Fluoroquinolone
Generation
Cephalosporin
a. Neisseria meningitides
ii. We look at PCN MIC

PCN MIC (mcg/ml) Therapy Alternative

< 0.1 PCN G or Ampicillin 3rd Generation
Cephalosporin,
Chloramphenicol
0.1 – 1 3rd Generation Fluoroquinolone,
Cephalosporin Meropenem
 b. Haemophilus influenzae
iii. Our therapy is dependent on resistance (B-Lactamase)

Therapy Alternative
B-Lactamase Ampicillin 3rd Generation
Negative Cephalosporin, cefepime,
Chloramphenicol,
Fluoroquinolone
B-Lactamase Positive 3rd Generation Cefepime,
Cephalosporin Chloramphenicol,
Fluoroquinolone

c. Staphylococcus aureus
iv. Also dependent on resistance (Methicillin resistant)

Therapy Alternative
Methicillin Nafcillin or oxacillin Vancomycin, meropenem
susceptible
Methicillin Vancomycin TMP/SMX, linezolid
resistant

Dosing in bacterial meningitis

When dosing antibiotics it is important to think about what we have to overcome: THE BLOOD BRAIN
BARRIER! → we use high doses!

- In the presence of meningitis there is inflammation

o The inflammation allows for more penetration into the BBB
▪ As the inflammation goes away it is harder to penetrate, so it is important to
continue the higher doses throughout therapy
o Drug characteristics that help cross the BBB
▪ ________________
▪ ________________
▪ ________________
▪ ________________

Role of Adjunctive Dexamethasone Therapy:

- Reason:
o In animal studies, the inflammatory response in the subarachnoid space during bacterial
meningitis is a major factor for morbidity and mortality
- Data:

Infants and Children:

o Available evidence shows that the addition of dexamethasone in infants and children
with H. influenza type b meningitis is beneficial!
▪ Give it PRIOR TO or WITH the first antimicrobial dose
➢ IF already gave first dose of ABX, do not give Dexamethasone (no
benefit)
▪ 0.15mg/kg Q6h for 2-4 days

Adults:

o Addition of dexamethasone is recommended in suspected strep. Pneumococcal

meningitis
▪ 0.15mg/kg Q6h for 2-4 days
➢ 10-20 mins prior to ABX or WITH ABX
o Data is inadequate for other pathogens

Lets Dig Deeper on Medications Used

• Cephalosporins
o H. Influenzae type B meningitis
▪ Chloramphenicol = Resistance!
• 3rd Generation Cephalosporin are the DOC
o Also good to treat aerobic gram negative bacilli
▪ E. coli or Klebsiella
o Ceftazidime
▪ Has shown efficacy against pseudomonas meningitis
 o Cefepime
▪ Shown to be safe and effective in infants and children
▪ Also covers for Enterobacter and pseudomonas species
• Vancomycin
o Used in penicillin resistant pneumococci
o Meningitis caused by higher penicillin and cephalosporin resistant strain
▪ Vancomycin should be used in combination with _____________
▪ Not used as monotherapy
• Rifampin
o Good CSF penetration
o Activity against many pathogen
o HOWEVER
▪ Resistance rapidly develops
▪ MUST be used with other antimicrobial agents
o When to use
▪ Susceptible organisms and there is a delay in response
▪ Shunt infections caused by ____________ combined with vancomycin
• Carbapenems
o Two have been studied
▪ Imipenem
• Seizure activity was high → Not recommended in most patient
▪ Meropenem
• Adults and children
• Alternative to ceftriaxone
• Can be used in cephalosporin resistant strains
• Can be used in ESBL producing bacteria
• Fluoroquinolones
o Used in gram negative infections (especially Cipro)
o Should be reserved for MDR gram negative bacilli
o HAVE NOT BEEN STUDIED IN NEWBORNS OR CHILDREN
▪ Should only be used in this group if not responding to therapy

Meningitis from a CSF shunt

• Shunt needs to be removed, some external drainage needs to be removed, and ABX are needed
o This is the most effective treatment
Duration of Therapy:

Depends on the pathogen!

Organism Duration (Days)

Neisseria meningitides 7
Haemophilus influenza 7
Streptococcs pneumoniae 10-14
Streptococcus agalactiae 14-21
Aerobic gram negative bacilli 21
Listeria monocytogenese >21

Sources

Allan R. Tunkel, Barry J. Hartman, Sheldon L. Kaplan, Bruce A. Kaufman, Karen L. Roos, W. Michael
Scheld, Richard J. Whitley, Practice Guidelines for the Management of Bacterial Meningitis, Clinical
Infectious Diseases, Volume 39, Issue 9, 1 November 2004, Pages 1267–
1284, https://doi.org/10.1086/425368