Community-Acquired Bacterial Meningitis

Question 1

What is meningitis?

Answer 1

Inflammation of the (lepto)meninges

Meninges - 3 protective layers that protect the brain and spinal cord (Dura Mater, Arachnoid, Pia Mater)

Leptomeninges - Arachnoid and Pia Mater, in between there is the subarachnoid space which contains cerebrospinal fluids

Question 2

Meningitis is inflammation of the brain (T/F)

Answer 2

False

Inflammation of the brain is encephalitis
Inflammation of the (lepto)meninges is meningitis
Inflammation of both is meningoencephalitis

Question 3

What are the 3 causes of meningitis?

Answer 3

1. Infection

• Bacteria (septic)
• Virus (enterovirus, herpes)
• Others: Fungal (cryptococci), Parasites (malaria), Mycobacterium (TB), Syphilis

2. Drugs

• Trimethoprim/sulfamethoxazole
• Ibuprofen

3. Autoimmune disease

Question 4

What is the incidence of bacterial meningitis?

Answer 4

• More common in developing countries compared to high-income countries (geographical region)
• More common in males than females
• More common in children and infants (immunity not yet well-developed)

Question 5

Explain the pathogenesis and risk factors of bacterial meningitis

Answer 5

1. Risk factors: immune deficiency, prolonged close contact, travel to endemic areas
2. Predispose to infection and colonization by bacteria that can cause meningitis
3. Bacteria gain entry into the body via various mechanisms (also risk factors):

• Invasion of mucosal surface (e.g., respi tract), then hematogenous spread to brain
• Spread from para-meningeal focus (otitis media, sinusitis)
• Penetrating head trauma
• Anatomic defects in meninges
• Previous neurosurgical procedures

4. In susceptible host, bacteria enter the CNS and colonize the meninges (esp arachnoid)

Question 6

What are some predisposing (risk factors) for bacterial meningitis?

Answer 6

• Head trauma
• CNS shunts
• Neurosurgical patients
• Cerebrospinal fluid fistula or leak
• Local infections (sinusitis, otitis media, pharyngitis)
• Immunosuppression
• Splenectomized patients
• Congenital defects

Question 7

1. Confirm presence of infection

Describe the clinical presentation of bacterial meningitis

Answer 7

1. Symptoms

=> General systemic symptoms: fever, chills etc.

=> BM symptoms:

• Classic triad: headache, backache, nuchal (neck) rigidity
• Mental status changes (irritability)
• Photophobia
• N&V, anorexia, poor feeding habits (esp infants)
• Petechiae or purpura (Neisseria meningitidis)

2. Physical signs

• Kernig sign: stiff hamstring, back pain when hip flexed to 90 degrees
• Brudzinski sign: stiff neck, hips and knees flex when neck lifted
• Bulging fontane: rather than normal induration [INFANTS]

Question 8

1. Confirm presence of infection

How to diagnose bacterial meningitis?

Answer 8

1. History and physical examination (signs and symptoms)
2. Blood cultures
3. Lumbar puncture (draw out CSF from L3/L4)
   - Elevated opening pressure
   - CSF composition
   - CSF gram stain and culture
   - CSF PCR
4. Lab findings
   - General labs (signs of systemic infection, but NON-SPECIFIC for BM): WBC, neutrophils, CRP, PCT
5. Radiology - Brain imaging (CT scan, MRI)
   - NOT required for diagnosis of meningitis, but typically done to evaluate differential diagnosis and complications (e.g., stroke, brain abscess)
   - (rare) in pt with concern for brain shift due to mass lesion, do brain imaging (e.g., CT scan/MRI) before LP to reduce risk of brain herniation during LP

Question 9

1. Confirm presence of infection

Elaborate on the CSF composition in bacterial meningitis in contrast to normal and viral meningitis

Answer 9

1. CSF turbidity
   - Normal: clear
   - Viral: clear
   - Bacterial: turbid
2. Glucose
   - Normal: 2.6-4.5, CSF:Blood >0.66
   - Bacterial: very low, CSF:Blood <0.4
   - Viral: normal or slightly low
3. Protein
   - Normal: <0.4g/L
   - Bacterial: >1.5g/L (raised)
   - Viral: normal to mildly raised
4. WBC
   - Normal: <5 cells/mm3
   - Bacterial: >100 cells/mm3 (predominantly neutrophils, pleocytosis)
   - Viral: 5-1000 cells/mm3 (predominantly lymphocytes)

Question 10

2. Identification of pathogens

List the common pathogens according to patient’s age group

Neonates <1month

Answer 10

Neonates <1month
- Streptococcus Agalactiae (Grp B)
- E. coli
- Listeria monocytogenes

Question 11

2. Identification of pathogens

List the common pathogens according to patient’s age group

Infants and childrens (1-23months)

Answer 11

Infants and childrens (1-23months)
- Streptococcus Agalactiae (Grp B)
- E. coli
- Streptococcus pneumoniae
- Neisseria meningitidis

Question 12

2. Identification of pathogens

List the common pathogens according to patient’s age group

Children and adults (2-50y)

Answer 12

Children and adults (2-50y)
- Streptococcus pneumoniae
- Neisseria meningitidis

Question 13

2. Identification of pathogens

List the common pathogens according to patient’s age group

Adults (>50y)

Answer 13

Adults (>50y)
- Streptococcus pneumoniae
- Neisseria meningitidis
- Aerobic GNR (E. coli, Klebsiella)
- Listeria monocytogenes

Question 14

2. Identification of pathogens

Which pathogen is most commonly found in neonates <1month and adults >50years?

Answer 14

Listeria monocytogenes

Question 15

2. Identification of pathogens

Why is Streptococcus Agalactiae common amongst neonates, infants, and childrens <23months?

Answer 15

Grp B Streptococcus Agalactiae is common colonization in vulvovaginal area of pregnant women, hence can colonize infants at birth

Question 16

2. Identification of pathogens

What are the two key organisms in bacterial meningitis and where do they commonly come from?

Answer 16

Streptococcus Pneumonia
Neisseria meningitidis

Both are habitants of the nasopharynx

Question 17

2. Identification of pathogens

Describe Listeria monocytogenes
- Morphology
- Where it is commonly found

Answer 17

Listeria monocytogenes is a gram-positive intracellular rod

Found in moist environment, replicate well in refrigerator temperature, commonly linked to food-borne disease outbreak (hence, may find in cold deli meats, unpasteurized dairy products)

Question 18

2. Identification of pathogens

Describe Neisseria meningitidis
- Morphology
- Where it is commonly found

Answer 18

Neisseria meningitidis is a fastidious, encapsulated, aerobic gram-negative diplococcus

It is a habitant of the nasopharynx of healthy individuals

Question 19

3. Selection of antimicrobial and regimen

Antibiotics for bacterial meningitis are given via the _____ route

Answer 19

IV route (to achieve high conc. in CSF)

Question 20

3. Selection of antimicrobial and regimen

What are the 3 main considerations for antibiotics choice for use in meningitis?

Answer 20

1. Must distribute to CSF and achieve adequately high CSF conc. (high dose + IV)
2. Active against likely pathogen
3. Should not aggravate CNS morbidity (avoid drugs that cause seizures)

• E.g., Meropenem over imipenem as imipenem has higher risk of seizures
• E.g., B-lactam dose adjusted in renal impairment as high conc. of B-lactam antibiotic in blood can cause neurotoxicity and seizures

Question 21

3. Selection of antimicrobial and regimen

What is the antibiotic of choice used to cover Listeria Monocytogenes?

Answer 21

Ampicillin

Question 22

3. Selection of antimicrobial and regimen

When should empiric antibiotic be started for bacterial meningitis?

Answer 22

Start ASAP within 1h

*LP should be done before antibiotic is started (to collect proper CSF)
*However, it should not be a reason to delay antibiotic treatment

Question 23

3. Selection of antimicrobial and regimen

Discuss the empiric antibiotic choice for neonates (<1month)

Answer 23

1. Neonates <1month
   - Streptococcus Agalactiae (Grp B)
   - E. coli
   - Listeria monocytogenes

IV Ampicilin 2g q4h (covers Listeria, Strep Agalactiae, E. coli)
+
IV Ceftriaxone 2g q12h (covers Strep Agalactiae, E. Coli)

Question 24

3. Selection of antimicrobial and regimen

Discuss the empiric antibiotic choice for infants and childrens (1-23 months)

Answer 24

2. Infants and childrens (1-23months)
   - Streptococcus Agalactiae (Grp B)
   - E. coli
   - Streptococcus pneumoniae
   - Neisseria meningitidis

IV Ceftriaxone 2g q12h (covers Strep Agalactiae, E. Coli, Strep Pneumo, Neisseria)
+
IV Vancomycin 25-30mg/kg LD, 15mg/kg q8-12h, to achieve AUC/MIC 400-600 (covers penicillin and cephalosporin resistant Strep Pneumo)

Question 25

3. Selection of antimicrobial and regimen Discuss the empiric antibiotic choice for children and adults (2-50y)

Answer 25

3. Children and adults (2-50y) - Streptococcus pneumoniae - Neisseria meningitidis IV Ceftriaxone 2g q12h (covers Strep Pneumo, Neisseria) + IV Vancomycin 25-30mg/kg LD, 15mg/kg q8-12h, to achieve AUC/MIC 400-600 (covers penicillin and cephalosporin resistant Strep Pneumo)

Question 26

3. Selection of antimicrobial and regimen Discuss the empiric antibiotic choice for adults (>50y)

Answer 26

4. Adults (>50y) - Streptococcus pneumoniae - Neisseria meningitidis - Aerobic GNR (E. coli, Klebsiella) - Listeria monocytogenes IV Ceftriaxone 2g q12h (covers Strep Pneumo, Neisseria, GNR) + IV Vancomycin 25-30mg/kg LD, 15mg/kg q8-12h, to achieve AUC/MIC 400-600 (covers penicillin and cephalosporin resistant Strep Pneumo) + IV Ampicilin 2g q4h (covers Strep Pneumo, Neisseria, Listeria, GNR)

Question 27

3. Selection of antimicrobial and regimen Discuss the culture-directed antibiotic choice for Streptococcus pneumoniae *Consider Penicillin and Cephalosporin resistance *State the duration of therapy

Answer 27

Streptococcus Pneumoniae (Duration of treatment: 10-14 days) Penicillin susceptible: - IV Ampicillin 2g q4h - IV Penicillin G 4MU q4h Pencillin resistant, but Cephalosporin susceptible: - IV Ceftriaxone 2g q12h Pencillin and Cephalosporin resistant: - IV Vancomycin + Rifampicin 300mg q12h

Question 28

3. Selection of antimicrobial and regimen Discuss the culture-directed antibiotic choice for Neisseria Meningitidis *Consider Penicillin resistance or mild allergy *State the duration of therapy

Answer 28

Neisseria Meningitidis (Duration of treatment: 5-7 days) Penicillin susceptible: - IV Ampicillin 2g q4h - IV Penicillin G 4MU q4h Penicillin resistant, mild allergy (e.g., rash): - IV Ceftriaxone 2g q12h *If severe allergy (e.g., anaphylaxis), get allergist involve in selection of abx regimen

Question 29

3. Selection of antimicrobial and regimen Discuss the culture-directed antibiotic choice for Listeria Monocytogenes *Consider Penicillin allergy *State the duration of therapy

Answer 29

Listeria Monocytogenes (Duration of treatment: >=21 days) Penicillin susceptible: - IV Ampicillin 2g q4h - IV Penicillin G 4MU q4h Penicllin allergy: - IV Co-trimoxazole - IV Meropenem 2g q8h

Question 30

3. Selection of antimicrobial and regimen Discuss the culture-directed antibiotic choice for Grp B Streptococcus (Strep agalactiae) *Consider Penicillin mild allergy *State the duration of therapy

Answer 30

Streptococcus agalactiae (Duration of therapy: 14-21 days) Penicillin susceptible: - IV Ampicillin 2g q4h - IV Penicillin G 4MU q4h Penicillin mild allergy: - IV Ceftriaxone 2g q12h

Question 31

3. Selection of antimicrobial and regimen If culture is unavailable, what should be the duration for empiric treatment?

Answer 31

At least 14 days of empiric antibiotic, may extend depending on patient condition

Question 32

3. Selection of antimicrobial and regimen Discuss the risks and benefits of adjunctive dexamethosone therapy in bacterial meningitis

Answer 32

Adjunctive Dexamathosone Therapy Benefits: - Less hearing loss and other neurologic sequelae in H. influenzae and S. pneumoniae meningitis - Decreased mortality in S. pneumoniae meningitis Risk: - May decrease antibiotic penetration (less inflammation of meninges, BBB less leaky, less antibiotic conc. in CSF) - ADR of Dexamethasone: mental status changes, hyperglycemia, hypertension

Question 33

3. Selection of antimicrobial and regimen In which group of patients with bacterial meningitis is adjunctive dexamethosone therapy recommended for?

Answer 33

Patients beyond the neonatal age (6 weeks onwards)

Question 34

3. Selection of antimicrobial and regimen What is the dosage and administration of adjunctive dexamethosone therapy?

Answer 34

Adult Dose: 10mg q6h for up to 4 days Administration: 10-20min before or at the same time as first dose of antibiotics (possibly within 4h or even 12h of Abx use) - Reason for administration before Abx: abx can cause more inflammation hence we want to prevent this

Question 35

3. Selection of antimicrobial and regimen In what cases is Dexamethosone stopped before 4 days of use?

Answer 35

If CSF culture shows negative for H. influenza or S. pneumoniae, then Dexamethasone is stopped as there is no benefit in other bacterial causes. If pt is not having bacterial meningitis, Dexamethasone is stopped as well.

Question 36

4. Monitor response - Therapeutic response - ADR - Morbidity

Answer 36

Therapeutic response - Most pt will improve within 48h - If not, brain imaging is indicated to detect cerebrovascular complications (e.g., stroke, brain abscess) - No need to repeat microbiological test if pt improve clinically ADRs of antibiotics - E.g., B-lactam (seizures at high blood conc.) - renal dose adjustment to prevent - E.g., Rifampicin - orange discoloration of bodily fluids, hepatotoxicity, flu-like syndromes, cutaneous reactions, GI effects, CYP450 inducer Morbidity - Morbidity is common in meningitis - Focal neurological deficits can lead to hearing impairment, cognitive impairment, seizures - After BM infection, adults are at high risk of long-term neurological and neuropsychological deficits that impair QoL

Question 37

Discuss Chemoprophylaxis for close contacts of Neisseria Meningitidis infected individuals *Meningococcal vaccination is available but not compulsory or part of immunization programs in Singapore

Answer 37

For close contacts, and exposure to oral secretions of index case, choose one of the following for chemoprophylaxis: Rifampicin PO - Adults: 600mg q12h, 4 doses - Children: 10mg/kg q12h, 4 doses - Infants <1month: 5mg/kg q12h, 4 doses Ciprofloxacin PO - Adults: 500mg, 1 dose - NOT for use in children <18yo Ceftriaxone (IM inj) - 125-250mg injection, 1 dose