Meningitis

 The brain and spinal cord are

protected by three membranes
called meninges: the outermost
dura mater, the middle arachnoid

mater, and the innermost pia mater.

 The space between the arachnoid

mater and the pia mater is known as
the subarachnoid space, which contains
cerebrospinal fluid (CSF).

 CSF, approximately 150mL in a normal

individual, is produced by the choroid
plexuses and vascular structures in the
ventricles of the brain.
  CSF flows from the ventricles to the subarachnoid space through
communicating apertures.

 From the subarachnoid space, CSF circulates over the surface of the brain
and spinal cord.

 The volume of CSF is regulated by its absorption into the bloodstream

through structures called arachnoid villi located in the subarachnoid space.

 Infective meningitis is an inflammation of the arachnoid and pia mater

caused by bacteria, viruses, fungi, or protozoa present in the CSF.

 Meningitis is a serious infectious disease associated with significant mortality

and the risk of severe complications in survivors

Aetiology and Epidemiology of Meningitis:

 Approximately 1500 cases of meningitis are reported annually in the UK.

 The actual incidence of meningitis is likely higher than reported.

 Viral meningitis is the most common form and is generally less severe than
bacterial or fungal meningitis.

II. Bacterial Meningitis

 Predominantly affects young children, with 40-50% of cases occurring in the

first four years of life.

 Two bacteria, Neisseria meningitidis (meningococcus) and Streptococcus

pneumoniae (pneumococcus), account for about 75% of cases.

 The prevalence of micro-organisms causing meningitis varies with age and

underlying health conditions.
A. Neisseria meningitidis - Most common cause of bacterial meningitis from
infancy to middle age. - Different serogroups exist, including A, B, C, W135, and Y. -
Serogroup B is currently responsible for over 80% of meningococcal disease cases
in the UK. - Vaccination against serogroup C is included in routine immunization,
but no vaccine is available for serogroup B.

B. Streptococcus pneumoniae - Most common cause of meningitis in adults over

45 years of age. - Almost half of all pneumococcal meningitis cases occur in
children under 5 years. - Routine childhood immunization program includes
vaccination against common serotypes of S. pneumoniae.

C. Haemophilus influenzae type b (Hib) - Previously a major cause of bacterial

meningitis in children aged 3 months to 5 years. - Routine immunization since 1992
has almost eliminated Hib disease in the UK and other developed countries.

D. Other Causes - Group B streptococci are the most common cause of bacterial
meningitis in the neonatal period. - Other causes include Escherichia coli, Listeria
monocytogenes, Staphylococcus aureus, enterococci, and others. L.
monocytogenes is also an occasional cause of meningitis in immunocompromised
patients. Meningitis can also occur as a complication of neurosurgery, especially in
patients who have ventriculoatrial or ventriculoperitoneal shunts. Coagulase-
negative staphylococci are the major causes of shunt-associated meningitis, but
other bacteria are important, including Enterobacteriaceae and S. aureus.
Meningitis due to S. aureus may also be secondary to trauma, or local or
haematogenous spread from another infective focus. Meningitis may also be a
feature of multisystem bacterial diseases such as syphilis, leptospirosis and Lyme
disease-

III. Tuberculous Meningitis

 The incidence of tuberculous meningitis has declined in developed countries

along with tuberculosis.
  It can occur as part of primary infection or as a result of recrudescence of a
previous infection.

IV. Viral Meningitis

 Human enteroviruses (e.g., echoviruses, Coxsackie viruses) account for

around 70% of viral meningitis cases in the UK.

 Herpes simplex and varicella-zoster viruses are other common causes.

 Mumps virus and human immunodeficiency viruses can occasionally cause

viral meningitis.

V. Fungal Meningitis

 Rare in individuals without underlying diseases in Europe.

 Candida species can cause shunt-associated meningitis.

 Cryptococcus neoformans is a significant cause in patients with late-stage

HIV infection and T-cell defects.

 Cryptococcus is the leading cause of infective meningitis in sub-Saharan

African countries with high HIV prevalence.

 Infections with other fungi like Coccidioides immitis and Histoplasma

capsulatum are endemic in certain regions.

I. Pathophysiology of Bacterial Meningitis

A. Nasopharyngeal Colonization

- Most cases of bacterial meningitis are preceded by colonization of the

nasopharynx by the causative organism.

- In the majority of colonized individuals, the infection does not progress further.
- Susceptible individuals experience invasion of the submucosa as the organism
bypasses host defenses.

B. Routes of Microorganism Spread

- Microorganisms can reach the meninges through various routes:

1. Direct spread from the nasopharynx.

2. Blood-borne spread from other sites of colonization or infection.

3. Abnormal communications with the skin or mucous membranes, such as skull

fractures or anatomical defects.

4. Spread from an infected adjacent focus, e.g., brain abscess, tuberculoma,

infected paranasal air sinus, or middle ear infection.

C. Invasion and Inflammation

- The organism invades the subarachnoid space, leading to widespread infection

and triggering meningeal inflammation.

- Cerebral tissue is typically not directly involved, although cerebral abscess may
occur in certain types of meningitis.

D. Virulence Factors

- Microorganisms causing meningitis possess virulence factors facilitating their

pathogenicity, including:

1. Attachment to host mucosal surfaces.

2. Evasion of phagocytosis and other host defenses.

3. Invasion of the meninges.

4. Disruption of the blood-brain barrier.

5. Induction of pathophysiological changes in the cerebrospinal fluid (CSF) space.

6. Secondary brain damage.

E. Effects of Infection

- Vascular endothelial injury and increased blood-brain barrier permeability occur,

allowing blood components to enter the subarachnoid space.

- This contributes to cerebral edema and elevated CSF protein levels.

- Neutrophils migrate from the bloodstream to the CSF in response to the cytokine
response.

- Cerebral edema leads to intracranial hypertension and reduced cerebral blood

flow.

- Anaerobic metabolism occurs, resulting in increased lactate and decreased

glucose concentrations.

- If left untreated, this uncontrolled process can cause transient neuronal

dysfunction or permanent neuronal injury.

II. Notes on Other Types of Meningitis (Viral and Fungal)

 The provided text does not include specific pathophysiological details for
viral or fungal meningitis.
 Viral meningitis is generally less severe and is caused by various viruses, with
enteroviruses being the most common.
  Fungal meningitis is rare in individuals without underlying diseases in
Europe, but certain fungi can cause meningitis in specific regions or
immunocompromised individuals.

I. Clinical Manifestations of Acute Bacterial Meningitis

A. Common Symptoms - Sudden-onset headache - Neck stiffness (nuchal rigidity) -

Photophobia (sensitivity to light) - Fever - Vomiting

B. Kernig's Sign - Positive Kernig's sign may be present. - Kernig's sign is resistance
to leg extension when the hip is flexed, indicating meningeal irritation in the
lumbar area.

C. Complications and Additional Symptoms - Septicaemia can occur as a

complication, leading to septic shock. - Hemorrhagic skin rash, although not
pathognomonic, is highly suggestive of meningococcal infection. - Untreated
patients with bacterial meningitis rapidly deteriorate, experiencing seizures, focal
cerebral signs, cranial nerve palsies, and eventually obtundation (reduced alertness)
and loss of consciousness, which can be fatal.

II. Clinical Manifestations of Meningitis in Infants

A. Early Signs - In infants, early physical signs are often nonspecific and may include
fever, diarrhea, lethargy, feeding difficulties, and respiratory distress.

B. Late Signs - Focal signs, such as seizures or a bulging fontanelle (soft spot on the
baby's head), usually occur at a later stage.

III. Clinical Manifestations of Viral Meningitis

 Acute onset of low-grade fever, headache, photophobia, and neck stiffness.

 Patients with viral meningitis typically remain alert and oriented unless they
develop encephalitis.
IV. Clinical Manifestations of Tuberculous and Fungal Meningitis

 Tuberculous and fungal meningitis often have a more indolent (slow-

developing) course compared to acute bacterial meningitis.

 Early stages are characterized by general symptoms such as malaise, apathy,

and anorexia.

 As the diseases progress, symptoms and signs more typical of meningitis

usually appear.

Diagnosis of Meningitis:

1. Definitive Diagnosis:

 Diagnosis of meningitis is established by detecting the causative organism,

demonstrating biochemical changes, and observing a cellular response in
the cerebrospinal fluid (CSF).

2. Lumbar Puncture:

 CSF is obtained through lumbar puncture, where a needle is inserted

between the third and fourth lumbar vertebrae into the subarachnoid space.

 Lumbar puncture should be approached with caution in patients with

intracranial hypertension to avoid precipitating or worsening brain
herniation.

 If neurological abnormalities are present, a CT scan should be performed

before performing lumbar puncture.

3. Normal CSF Parameters:

 In a healthy individual, CSF is a clear, colorless fluid.

 CSF pressure in the lumbar region of the spinal cord is typically between 50-
150 mmH2O.
 Normal CSF may contain up to 5 cells/μL, protein concentration up to 0.4
g/L, and glucose concentration at least 60% of the blood glucose (usually
2.2-4.4 mmol/L).

4. CSF Analysis in Meningitis Diagnosis:

 Table 38.1 provides information on how cell count and biochemical

measurements in CSF can help determine the type of organism causing
meningitis.

5. Microscopic Examination:

 Bacterial and fungal meningitis may reveal the presence of organisms in

Gram-stained smears of the CSF.

 Gram stain appearance can differentiate between common causes of

bacterial meningitis.

 Special stains like the Ziehl-Neelsen method are required to visualize

mycobacteria, although direct microscopy is often inconclusive in
tuberculous meningitis.

 India ink staining is useful for visualizing cryptococci and their capsules.

6. Culture and Non-Culture-Based Methods:

 CSF should be cultured to confirm the identity of the causative organism,

allowing for further investigations such as antibiotic sensitivity testing and
typing.

 Special cultural techniques are necessary for mycobacteria, fungi, and

viruses.

 Blood culture should always be obtained in suspected bacterial meningitis,

and a nasopharyngeal swab culture may be helpful in suspected
meningococcal disease.
  Molecular amplification techniques, such as polymerase chain reaction
(PCR), are increasingly used to detect specific pathogens like meningococci,
pneumococci, Mycobacterium tuberculosis, herpes simplex viruses, and
enteroviruses.

 Serum antibody testing and interferon-gamma release assay can aid in the
diagnosis of specific pathogens like N. meningitidis and M. tuberculosis.

Treatment (refer to book too)

Antimicrobial Therapy for Acute Bacterial Meningitis - Pharmacokinetic

Considerations

Acute bacterial meningitis is a medical emergency that requires prompt

administration of antibiotics. In addition to antibiotics, adjunctive therapy and
preventive measures may be considered for certain forms of meningitis. This
discussion focuses on the pharmacokinetic considerations of antimicrobial therapy
in meningitis.

Route of Antibiotic Entry into CSF: The primary route of entry of antibiotics into the
cerebrospinal fluid (CSF) is through the choroid plexus. An alternative route
involves penetration from the capillaries of the central nervous system into the
extracellular fluid, ventricles, and subarachnoid space. However, the passage of
antibiotics into the CSF depends on several factors.
Factors Affecting Antibiotic Penetration:

1. Meningeal Inflammation and Blood-Brain Barrier: The degree of meningeal

inflammation and the integrity of the blood-brain barrier, which is formed by
capillary endothelial cells, influence antibiotic penetration into the CSF.

2. Properties of the Antibiotic: a. Lipid Solubility: Antibiotics with higher lipid

solubility have better penetration into the CSF. The choroidal epithelium is
highly impermeable to lipid-insoluble molecules.

b. Ionic Dissociation: Antibiotics that undergo ionic dissociation at blood pH tend

to penetrate the CSF more effectively.

c. Protein Binding: The extent of protein binding can affect the availability of
antibiotics for penetration into the CSF.

d. Molecular Size: Smaller molecules generally have better penetration compared

to larger ones.

e. Serum Concentration: The concentration of the drug in the serum also plays a
role in its ability to enter the CSF.

Categories of Antimicrobials Based on CSF Penetration: Antimicrobials can be

categorized into three groups based on their ability to penetrate the CSF:

1. High Penetration, Regardless of Meningeal Inflammation:

 Chloramphenicol

 Metronidazole

 Isoniazid

 Pyrazinamide

2. Penetrate when Meninges are Inflamed (Higher Doses may be required):

 Most β-lactam antibiotics (e.g., penicillins, cephalosporins)

  Quinolones

 Rifampicin

3. Poor Penetration under all Circumstances:

 Aminoglycosides

 Vancomycin

 Erythromycin

Recommended Empirical Antimicrobial Therapy Regimens for Acute Bacterial

Meningitis

In cases of acute bacterial meningitis, empirical antimicrobial therapy needs to be

initiated promptly, even before the causative organism or its antibiotic sensitivities
are known. This section discusses the recommended regimens for empiric
antimicrobial therapy based on different patient groups in acute bacterial
meningitis.

1. Neonates and Infants Aged Below 3 Months:

 Ampicillin plus Cefotaxime or Gentamicin: This combination covers

common pathogens, including Group B Streptococcus, Escherichia
coli, and Listeria monocytogenes.

2. Immunocompetent Older Infants, Children, and Adults:

 Cefotaxime or Ceftriaxone: These third-generation cephalosporins

provide coverage against Streptococcus pneumoniae, Neisseria
meningitidis, and Haemophilus influenzae, the most common
pathogens in this group.

3. Immunocompromised Patients:
  Cefepime or Meropenem: These broad-spectrum antibiotics cover a
wide range of pathogens, including Streptococcus pneumoniae,
Neisseria meningitidis, Haemophilus influenzae, and also account for
potential drug-resistant organisms in immunocompromised
individuals.

4. Patients with Ventricular Shunts:

 Vancomycin plus Cefepime or Meropenem: This combination covers

common pathogens, including Staphylococcus aureus and coagulase-
negative Staphylococci, as well as potential Gram-negative organisms.

Additional Considerations:

 Adjunctive Therapy: In some cases, adjunctive therapy with corticosteroids

may be considered. Dexamethasone is often given empirically before or with
the first dose of antibiotics in suspected bacterial meningitis, particularly in
cases of suspected Streptococcus pneumoniae meningitis.

 Duration of Therapy: The duration of antimicrobial therapy is typically 7-21

days, depending on the causative organism, clinical response, and other
factors. This decision is made on a case-by-case basis by the treating
physician.

Antibiotic Therapy for Meningitis in Neonates and Infants below 3 Months

Meningitis in neonates and infants aged below 3 months is primarily caused by

group B streptococci, Escherichia coli, other Enterobacteriaceae, and Listeria
monocytogenes. Empiric antimicrobial therapy for neonatal meningitis typically
involves a third-generation cephalosporin (such as cefotaxime or ceftazidime)
along with amoxicillin or ampicillin. However, the choice of regimen may vary
depending on regional practices and predominant pathogens.

1. Empiric Therapy for Neonates:

 Option 1: Third-generation Cephalosporin + Amoxicillin/Ampicillin:
 Cefotaxime or Ceftazidime (third-generation cephalosporin)
 Amoxicillin or Ampicillin (to cover Listeria monocytogenes)
 Option 2: Aminoglycoside + Penicillin or Amoxicillin/Ampicillin:
 Gentamicin (aminoglycoside)
 Benzylpenicillin, Ampicillin, or Amoxicillin (to cover group B streptococci and
Enterobacteriaceae)
2. Empiric Therapy for Infants Outside the Neonatal Period:
 Amoxicillin or Ampicillin + Cefotaxime or Ceftriaxone:
 Amoxicillin or Ampicillin (to cover Listeria monocytogenes)
 Cefotaxime

or
Ceftriaxone
(third-
generation

cephalosporin)
Note: Therapy with Amoxicillin or Ampicillin plus Gentamicin is unsuitable for this
age group due to inadequate coverage against Haemophilus influenzae.

Adjusting Therapy: Once the pathogen is identified, therapy can be tailored

accordingly. Adjustments may include narrowing the spectrum or changing
antibiotics based on the susceptibility profile of the isolated pathogen.
Dosages: Appropriate dosages for the recommended antibiotics can be found in
Table 38.2

Conclusion: In neonates and infants below 3 months, the most common pathogens
causing meningitis include group B streptococci, E. coli, other Enterobacteriaceae,
and L. monocytogenes. Empiric therapy should cover these pathogens adequately.
A combination of a third-generation cephalosporin and amoxicillin or ampicillin is
the preferred regimen in many centers. However, some centers may use an
aminoglycoside in combination with penicillin or amoxicillin/ampicillin. In infants
outside the neonatal period, the classic neonatal pathogens become less common,
and amoxicillin or ampicillin plus cefotaxime or ceftriaxone is the recommended
treatment. Adjustments in therapy can be made based on pathogen identification.
Careful consideration of appropriate dosages is essential for optimal treatment.

Antibiotic Therapy for Meningitis in Older Infants, Children, and Adults

Introduction: Meningitis in older infants, children, and adults is primarily caused by

Streptococcus pneumoniae, Neisseria meningitidis, and, in children below 5 years,
Haemophilus influenzae. The choice of antibiotics should cover these pathogens,
taking into account the increasing resistance rates and potential adverse effects of
certain antibiotics.

1. Empiric Therapy:

 Preferred Option: Third-generation Cephalosporin (e.g., Cefotaxime,

Ceftriaxone):

 Cefotaxime or Ceftriaxone (to cover S. pneumoniae, N.

meningitidis, and H. influenzae)

 Alternative Option: Combination Therapy:

 Third-generation Cephalosporin (Cefotaxime or Ceftriaxone) +

  Vancomycin (to cover penicillin-resistant S. pneumoniae)

 Rifampicin (may be used in combination with

cephalosporin and/or vancomycin)

 Chloramphenicol (alternative for penicillin-sensitive

strains, not recommended for penicillin-resistant
pneumococcal meningitis)

2. Specific Pathogens:

 N. meningitidis:

 Emergency administration of Benzylpenicillin (primary care

clinicians)

 Adult: 1200 mg; Children (10 years and above): 1200 mg;

 Children (1-9 years): 600 mg; Children (below 1 year): 300

mg

 Alternatives if allergic to penicillin: Cefotaxime or

Chloramphenicol

 S. pneumoniae:

 Combination Therapy: Third-generation Cephalosporin +

Vancomycin

 Other potential options: Rifampicin, Meropenem, Moxifloxacin,

Linezolid, Daptomycin (case reports)

 H. influenzae:

 Third-generation Cephalosporin (Cefotaxime or Ceftriaxone)

3. Monitoring and Considerations:

  Close observation of patients during treatment, monitoring C-reactive
protein (CRP)

 Repeat examination of CSF during therapy may be considered

Dosages:

 Exact dosages for specific antibiotics are not provided in the given
information. It is recommended to refer to reliable sources or consult a
healthcare professional for appropriate dosing guidelines.

Meningitis in older infants, children, and adults is primarily caused by S.

pneumoniae, N. meningitidis, and H. influenzae. Third-generation cephalosporins,
such as cefotaxime or ceftriaxone, are widely used as empiric therapy due to their
broad spectrum of activity. Adjustments in therapy may be required based on
regional resistance patterns and individual patient factors. Combination therapy
may be necessary for penicillin-resistant S. pneumoniae. Close monitoring and
careful consideration of alternative antibiotics may be necessary in challenging
cases. It is crucial to consult healthcare professionals and refer to appropriate
guidelines for precise dosing recommendations.

Chemoprophylaxis Against Meningococcal and Hib Infection

Chemoprophylaxis is recommended for individuals in close contact with patients

diagnosed with meningococcal or Haemophilus influenzae type b (Hib) infections.
The goal is to prevent the spread of the bacteria and subsequent infections. The
choice of antibiotics and the need for prophylaxis beyond household contacts
should be determined with expert advice. Ceftriaxone is effective in eliminating
nasopharyngeal carriage of meningococci, while rifampicin is effective against Hib.
Ciprofloxacin is widely recommended for its convenience and broad age range
suitability.

1. Meningococcal Infection Chemoprophylaxis:

  Indications: Close household contacts and others as determined by
expert advice.

 Antibiotics for Prophylaxis (Box 38.2):

 Ceftriaxone (recommended for the index case when used for

treatment)

 Ciprofloxacin (preferred due to single-dose convenience and

availability)

 Vaccination: Contacts receiving prophylaxis may require vaccination

against specific serogroups (C, A, W135, Y) but not the index case. No
vaccine is available for group B disease.

2. Hib Infection Chemoprophylaxis:

 Indications: Unimmunized child in the household.

 Antibiotics for Prophylaxis (Box 38.2):

 Rifampicin (proven effective in eliminating nasopharyngeal

carriage)

 Vaccination: Unimmunized household contacts below 4 years should

receive Hib vaccine. The index case should receive rifampicin and be
vaccinated, regardless of age.

 The specific dosages for antibiotics as chemoprophylaxis are not provided.

Consult reliable sources or healthcare professionals for appropriate dosing
guidelines.

 Ciprofloxacin is preferred for meningococcal prophylaxis due to its

convenience and lack of interactions with oral contraceptives.
  Anaphylactoid reactions have been reported with ciprofloxacin
chemoprophylaxis but are non-fatal.

 Expert advice should be sought for the decision to offer prophylaxis beyond
household contacts.

 Meningococcal group B accounts for about 70% of cases in Europe, and

there is currently no vaccine available for it.

 Rifampicin is the only antibiotic proven effective in eliminating

nasopharyngeal carriage of Hib.

Chemoprophylaxis plays a crucial role in preventing the spread of meningococcal

and Hib infections among close contacts. Ceftriaxone and ciprofloxacin are
recommended for meningococcal prophylaxis, with ciprofloxacin being preferred
due to its convenience. Rifampicin is effective for Hib prophylaxis. Vaccination
should also be considered for contacts based on specific serogroups or
unimmunized status. It is essential to consult healthcare professionals and refer to
appropriate guidelines for precise dosing recommendations and specific situations.

Antibiotics for Meningitis in Special Groups

1. Immunocompromised Neutropenic Patients:

 Causes of meningitis: Enterobacteriaceae, Pseudomonas aeruginosa,

and classic bacterial pathogens.

 Therapy: Broad-spectrum coverage with agents having good CSF

penetration.

 Meropenem is the drug of choice for meningitis in this setting.

 Other appropriate regimens are also available.

2. Patients with Cellular Immune Dysfunction:

  Causes of meningitis: Listeria monocytogenes and Cryptococcus
neoformans.

 Empirical antibacterial therapy:

Ampicillin or amoxicillin, along with
cefotaxime or ceftriaxone.

 Definitive treatment for listeria

meningitis: High-dose ampicillin or
amoxicillin with the addition of
gentamicin.

 Penicillin-allergic or ampicillin-
resistant cases require specialist
microbiological advice.

3. Splenectomized Patients:

 Susceptible to infections with

encapsulated bacteria (e.g., Streptococcus
pneumoniae, Haemophilus influenzae
type b).

 Standard therapy: Cefotaxime or

ceftriaxone.

4. Shunt-Associated Meningitis:

 Risk in patients with ventricular shunts; classified as internal or external

infections.

 Internal infections (majority of cases): Coagulase-negative

staphylococci.

 External infections: Staphylococcus aureus and Enterobacteriaceae.

  Management: Antibiotic therapy and shunt removal (controversial).

5. Tuberculous Meningitis:

 Early initiation of appropriate chemotherapy is crucial.

 Most antituberculous agents achieve effective concentrations in the

CSF.

 Adjunctive steroid therapy may be considered in severe cases.

 Early neurosurgical management of hydrocephalus is important.

6. Cryptococcal Meningitis:

 Standard treatment: Amphotericin B ± flucytosine for 6-10 weeks.

 Lipid formulations of amphotericin B may have fewer side effects.

 Alternative therapy: 2 weeks of amphotericin B and flucytosine

followed by fluconazole consolidation.

 Monitoring and management of intracranial pressure are essential.

 Fluconazole maintenance therapy for patients with HIV infection.

7. Viral Meningitis:
  Self-limiting condition; no specific
antiviral agents for enteroviruses.

 Herpes simplex and varicella-zoster

meningoencephalitis treated with
high-dose aciclovir.

Meningitis in special groups requires tailored

antibiotic therapy based on the underlying cause
and patient characteristics. Meropenem is often
the drug of choice for immunocompromised
neutropenic patients. Patients with cellular
immune dysfunction may require ampicillin or
amoxicillin with cefotaxime or ceftriaxone. Splenectomized patients should receive
therapy against encapsulated bacteria. Shunt-associated meningitis may require
shunt removal in addition to antibiotic treatment. Tuberculous and cryptococcal
meningitis have specific treatment regimens. Viral meningitis is usually self-
limiting, while herpes simplex and varicella-zoster meningoencephalitis are treated
with high-dose aciclovir.

Title: Steroids as Adjunctive Therapy in Bacterial Meningitis

1. Mechanism of Action:

- Corticosteroids, particularly dexamethasone, regulate components of the

inflammatory response and lower CSF hydrostatic pressure.

- They reduce inflammation and restore the blood-brain barrier.

- Corticosteroids may potentially reduce CSF penetration of antibiotics.

2. Benefits in Specific Forms of Bacterial Meningitis:

a. Tuberculous Meningitis and Haemophilus influenzae type b (Hib) Meningitis:

- Well-established benefits of corticosteroids in these forms of meningitis.

- Adjunctive therapy with corticosteroids is recommended.

b. Other Forms of Bacterial Meningitis:

- Historically, evidence of benefits from adjunctive steroid therapy has been less
compelling.

- Older studies had methodological flaws and failed to show a benefit.

- Recent research suggests significant benefits in adults with bacterial

meningitis.

3. Recent Evidence and Recommendations:

- Recent studies have shown that adjunctive dexamethasone therapy reduces

unfavorable outcomes in adults with bacterial meningitis.

- Dexamethasone should be given before or with the first dose of antibiotics.

- Corticosteroids significantly reduce mortality, severe hearing loss, and

neurological sequelae.

- Adjunctive dexamethasone therapy is now recommended for children and

adults with community-acquired bacterial meningitis, irrespective of the bacterial
etiology.
 - The treatment should be initiated before or with the first dose of antibiotics and
continued for 4 days.

- Recommended dosage: 10 mg of dexamethasone four times daily for 4 days in

adults, and 0.15 mg/kg four times daily for 4 days in children.

Conclusion:

Adjunctive therapy with corticosteroids, particularly dexamethasone, has

demonstrated benefits in specific forms of bacterial meningitis, such as tuberculous
meningitis and Hib meningitis. Recent evidence supports the use of adjunctive
dexamethasone therapy in community-acquired bacterial meningitis, regardless of
the bacterial etiology. The initiation of corticosteroid therapy before or with the
first dose of antibiotics and continuation for 4 days is recommended. However, the
potential impact on antibiotic penetration should be considered.

Intrathecal and Intraventricular Administration of Antibiotics

1. Intrathecal Administration:

 Intrathecal administration involves delivering antibiotics into the

lumbar subarachnoid space.

 Historically used to supplement systemic therapy, but now rarely used

due to limited evidence of efficacy.

 Low concentrations of antibiotics reach the ventricles, providing little

prevention against ventriculitis, a serious complication of meningitis.

2. Intraventricular Administration:

 Direct intraventricular administration of antibiotics is important in

certain types of meningitis.
  Used when antibiotics that poorly penetrate CSF (e.g., vancomycin or
aminoglycosides) are required.

 Commonly used in shunt-associated meningitis, where antibiotic-

resistant coagulase-negative staphylococci are major pathogens.

 Administered through an external ventricular drain when available.

3. Recommended Doses of Antibiotics:

 Intrathecal and intraventricular administration have different

recommended doses.

 For shunt-associated meningitis in adults with an extraventricular

drain: 15-20mg vancomycin per day.

 For neonates and children with shunt-associated meningitis: 10mg

vancomycin per day.

 Pediatric dose may be adjusted based on ventricular size (reduced:

5mg/day, increased: 15-20mg/day).
  If CSF is not draining freely, the dose frequency should be decreased
to once every 2-3 days.

 CSF vancomycin concentration should be measured after 3-4 days,

aiming for a trough concentration of <10mg/L.

 Recommended antibiotic doses are primarily based on anecdotal

experience.

Conclusion: Intrathecal administration of antibiotics is rarely used due to limited

evidence of efficacy. Intraventricular administration, on the other hand, plays a
crucial role in specific types of meningitis, particularly shunt-associated meningitis.
It allows for direct delivery of antibiotics into the ventricles, addressing poor CSF
penetration by certain agents. The recommended doses of antibiotics for
intraventricular administration vary, and adjustments may be needed based on
patient age and ventricular size. Monitoring CSF antibiotic concentrations is
important to ensure appropriate dosing.

Patient Care
Preventing person-to-person transmission of meningitis:

1. Isolation of Neonates with Meningitis: Neonates with meningitis should be

isolated to prevent the spread of infection to other patients. The causative
organisms can often be isolated from body fluids and feces, indicating the
potential for transmission.

2. Isolation for Meningococcal or Hib Meningitis: Patients with meningococcal

or Haemophilus influenzae type b (Hib) meningitis should be isolated until
after at least 48 hours of antibiotic therapy. These infections have a higher
risk of transmission, and isolation helps prevent the spread of the bacteria.

3. Asymptomatic Carriers and Contacts: Contacts of patients with

meningococcal or Hib meningitis may be asymptomatic carriers of the
bacteria and have the potential to transmit the infection to others or develop
invasive infection themselves.
4. Chemoprophylaxis: Chemoprophylaxis, the use of antibiotics to prevent
infection, is recommended for close contacts of patients with meningococcal
or Hib meningitis. This measure helps reduce the risk of transmission and
secondary cases. Ceftriaxone is often the treatment of choice for
chemoprophylaxis.

5. Vaccination: Vaccination is an important preventive measure for certain

types of meningitis. Vaccines against meningococcal and Hib infections are
available and can significantly reduce the risk of acquiring these diseases.
Routine immunization programs may include these vaccines for infants and
children.

6. Enhanced Infection Control Precautions: For most other types of meningitis,

the risk of person-to-person transmission is not significant, and enhanced
infection control precautions are not usually necessary. However, standard
infection control measures should still be followed to prevent the spread of
any potential pathogens.