Meningitis

Tirsit K.
March 2024
 Introduction
Anatomy and Physiology
• The brain and spinal cord are ensheathed by a protective covering known
as the meninges and suspended in cerebrospinal fluid (CSF)
• CSF--- a clear, colorless fluid providing nourishment, waste removal,
and protection to the brain
• The meninges consist of three layers of fibrous tissue:
• pia mater, arachnoid, and dura mater
• Subarachnoid space:
• Separates the pia mater from the more loosely enclosed arachnoid
membrane
• CSF resides here
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 Cont.….
• The term central nervous system (CNS) infections describes a variety of
infections involving the brain and spinal cord and associated tissues,
fluids, and membranes, including:
• Meningitis = inflammation of the meninges, specifically of the
subarachnoid space.
• Encephalitis = inflammation of the brain parenchyma
• Meningoencephalitis (encephalomyelitis) = inflammation of both
• Myelitis = inflammation of spinal cord parenchyma
• Encephalomyelitis= inflammation of the brain and spinal cord
parenchyma
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 Cont.…..
• Meningitis
• is an inflammatory disease of the meninges, the tissues
surrounding the brain and spinal cord, and is defined by an
abnormal number of white blood cells in the cerebrospinal
fluid (CSF). Or
• It is an inflammation of the membranes that surround the
brain and the spinal cord

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 Cont.….
Classification
• Based on duration of symptoms
• Acute ----- acute bacterial meningitis, viral meningitis
• Chronic --------- TB meningitis
• Based on etiology
• Bacterial
• Viral
• Fungal
• TB
• Parasitic

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 cont.….
Risk factors
• Respiratory tract infection
• Otitis media
• Head trauma
• High-dose steroids
• Splenectomy
• Sickle cell disease
• Immunoglobulin (Ig) deficiency)
• Immunosuppression
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Acute Bacterial meningitis
• Inflammation of the meninges surrounding the brain and
spinal cord pia arachnoid and subarachnoid matter
• With positive Gram stain CSF ,WBC count
>1000/microL with CSF glucose concentration <40
mg/dL

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Cont.….
Pathogenesis
• Hematogenous
• Dissemination of micro-organisms from a distant site of
infection---most common route.
• Direct invasion
• Contiguous focus of infection: otitis media,sinusitis
• Through anatomic abnormalities
• Head trauma
• Neurosurgical procedures
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 Cont.….
• Bacterial cell death causes the release of cell wall components such as
• lipopolysaccharide, lipid A(endotoxin),lipoteichoic acid, and
Teichoic acid
• These cell wall components cause capillary endothelial cells and CNS
macrophages to release cytokines (interleukin-1, tumor necrosis factor,
and other inflammatory mediators).

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 Cont.….
• Proteolytic products and toxic oxygen radicals cause an alteration of
the blood–brain barrier (BBB)
• BBB---a selective semi-permeable membrane between
the blood and the interstitium of the brain, allowing
cerebral blood vessels to regulate molecule and ion
movement between the blood and the brain.
• platelet-activating factor activates coagulation
• arachidonic acid metabolites stimulate vasodilation.

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 Cont.….
These events lead to
cerebral edema
elevated intracranial pressure
cerebrospinal fluid (CSF) pleocytosis
decreased cerebral blood flow
cerebral ischemia, and
Finally death.

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 Summery of pathophysiology

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Cont.….
Clinical presentation
• nuchal rigidity---Resistance of the extensor muscles of the
neck to being bent forwards (i.e., impaired neck flexion)
• altered mental status
• Chills,Vomiting,Photophobia,severe headache
• Kernig’s and Brudzinski’s signs may be present but are
poorly sensitive and frequently absent in children.
• Irritability,delirium, drowsiness, lethargy, and coma.
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Cont.….
In infants, manifestations may include
• fever,
• hypothermia,
• lethargy,
• respiratory distress,
• poor feeding,
• vomiting, diarrhea, seizures, restlessness, irritability, and/or bulging
fontanel

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 Cont.….
Diagnosis
• Lumbar puncture test
• CSF gram stain
• Blood Culture
• Imaging
• MRI
• CT
• Polymerase chain reaction(PCR)-if viral

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Lumbar puncture test
• performed in lower back, in the lumbar region.
• Contraindications for LP
• Elevated ICP and focal Neurologic deficit
• Severe cardio respiratory compromise
• Infection of the overlying skin
• Thrombocytopenia

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 Cont.….
Physical examination
• Neck stiffness---- the inflamed nerve roots and meninges of the
cervical region get stretched.
• Positive Kerning’s sign
• Positive Brudzinski’s sign
• Altered state of consciousness

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 cont.….
Differential diagnosis
• Aseptic meningitis
• Subdural hematoma
• Metastatic brain disease
• Encephalitis
• Tuberculosis meningitis
• Cerebral malaria
• Brain abscess
• Brain tumor
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 Management
Goal of therapy
• Eradication of infection
• Amelioration of signs and symptoms
• Prevention of neurologic sequelae, such as seizures, deafness,
coma, and death.

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 cont.….

General Principles
• avoidance of delay in administering therapy and the choice of
drug regimen.
• Antibiotic therapy should be initiated immediately after
lumbar puncture (LP) is performed if the clinical suspicion for
meningitis is high
• Delay in the administration of appropriate antibiotics can have
a deleterious effect on outcome for patients who are
deteriorating rapidly.

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Cont.….
• Antibiotic regimen — There are two general principles of
antibiotic therapy for bacterial meningitis
The agent(s) used must be bactericidal against the infecting
organism
The agent(s) used must be able to penetrate the blood-brain
barrier to reach a sufficient concentration in the CSF

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Cont.….

• Drug entry into CSF — Treatment of bacterial meningitis

requires adequate concentration of antibiotics in the CSF.
• Most drugs reach peak concentrations in the CSF that are only
10 to 20 percent of peak concentrations in the serum.
• This is because the blood-brain barrier blocks macromolecule
entry into the CSF, with small, lipophilic molecules
penetrating most easily.

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Cont.…..
Pretreatment Evaluation
Complete history and physical examination, cerebrospinal
fluid (CSF) examination
Glucose, protein, Gram stain and culture
Complete blood count (CBC) with differential and platelet
count
Blood urea nitrogen, and creatinine
Evaluation of clotting function is especially indicated if
petechiae are noted
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Cont.….
Supportive Measures
 Vital Signs every 15-30 min.
 Frequent Neurologic assessment
 Serum electrolytes
 Antipyretics
 Fluid restriction
 Coma care

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 Cont.….
• Seizure control
• Active SZ –arrest with diazepam 0.1 -0.3 mg/kg/IV
• Prevention of recurrence of seizure
• Phenytoin- 20mg/kg loading then 5mg/kg/ 24 hrs bid
• Phenobarbitone can be added for refractory SZ
• Shock
• IV NS/RL /

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Cont.….
Empirical therapy : neonates to age 1 month
• In the first month of life, the most common pathogens are GBS, E
coli and L monocytogenes.
• Primary treatment consists of a combination of ampicillin and
cefotaxime.
• Cefotaxime is 50 mg/kg IV every 6 hours, up to 12 g/day. +
Ampicillin
• Ampicillin dosages are as follows:
• Age 0-7 days – 50 mg/kg IV every 8 hours
• Age 8-30 days – 50-100 mg/kg IV every 6 hours
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cont.….
• Alternative treatment consists of ampicillin plus gentamicin.
• Gentamicin dosages are as follows:
• Age 0-7 days – 2.5 mg/kg IV or intramuscularly (IM) every
12 hours
• Age 8-30 days – 2.5 mg/kg IV or IM every 8 hours

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Cont.….
Age 1-3 months

The first-line agent is cefotaxime (50 mg/kg IV every 6 hours, up

to 12 g/day) or ceftriaxone (75 mg/kg initially, then 50 mg/kg
every 12 hours, up to 4 g/day) + ampicillin (50-100 mg/kg IV
every 6 hours).
An alternative agent is chloramphenicol (25 mg/kg orally or IV
every 12 hours) + gentamicin (2.5 mg/kg IV or IM every 8
hours).
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Cont.…

Age 3 months to 7 years

The most common microorganisms are S pneumoniae, N

meningitidis, and H influenzae.
Primary treatment is with either cefotaxime (50 mg/kg IV every 6
hours, up to 12 g/day) or ceftriaxone (75 mg/kg initially, then 50
mg/kg every 12 hours, up to 4 g/day).

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 Cont….

Age 7-50 years

• The most common microorganisms in bacterial meningitis are S

pneumoniae, N meningitidis, and L monocytogenes.
• Primary treatment consists of with either cefotaxime or ceftriaxone
plus vancomycin.
Pediatric dosing is as follows:
• Cefotaxime – 50 mg/kg IV every 6 hours, up to 12 g/day
• Ceftriaxone – 75 mg/kg initially, then 50 mg/kg every 12 hours, up
to 4 g/day
• Vancomycin – 15 mg/kg IV every 8 hours
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Cont.….
STG
• Up to 50 years
• Ceftriaxone 2gm IV BID + vancomycin 1gm IV BID 10-14
days
• > 50 years
• Ceftriaxone 2gm IV BID + vancomycin 1gm IV BID +
Ampicillin 2g IV q4h 21 days

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Cont.….
• Immunocompromised and Alcoholism
• vancomycin 1gm IV BID + Ampicillin 2g IV q4h +
Ceftazidime 2g IV q6-8h
• Hospital acquired , Post- neurosurgery , Penetrating head trauma
• vancomycin 1gm IV BID + Ceftazidime 2g IV q6-8h

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Cont.…
Adjuvant therapy
• Dexamethasone--- blunting the inflammatory response secondary
to bacterial lysis
• causes a significant improvement in CSF concentrations of
proinflammatory cytokines, glucose, protein, and lactate as well
as a significantly lower incidence of neurologic sequelae
commonly associated with bacterial meningitis.
• It should be administered prior to the first antibiotic dose and not
after antibiotics have already been started
• 0.15 mg/kg every 6 hours for 4 days.

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Cont.….
Duration of therapy
• 5-7 days for meningococcal meningitis
• 5-10days Neisseria meningitides
• 21 days E.coli
• 14-21 days Listeria monocytogenes
• 7-10 days for H. influenzae meningitis
• 10-14 days for pneumococcal meningitis

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Complications
• Complications of bacterial meningitis can be divided into
systemic and neurologic.
• Systemic complications, consequence of the bacteremia
• Septic shock
• Disseminated intravascular coagulation (DIC)
• Acute respiratory distress syndrome (ARDS)
• Septic arthritis are usually the.

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 Cont.….

• The neurologic complications of meningitis may be sudden or

gradual in onset and can appear at any time after the onset of
symptoms, including after the completion of therapy.
• Impaired mental status
• Cerebral edema and increased intracranial pressure
• Seizures
• Focal deficits (e.g., hearing loss, cranial nerve palsies,
hemiparesis or quadriparesis)

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Cont.…

• Cerebrovascular abnormalities
• Neuropsychologic impairment, developmental disability
• Subdural effusion or empyema
• Hydrocephalus
• Hypothalamic dysfunction

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Cont.….

Increased Intracranial Pressure

• Cytotoxic cerebral edema due to cell swelling to cell death
• Vasogenic cerebral edema due to cytokine induced increased
capillary vascular permeability
• Interstitial cerebral edema increased hydrostatic pressure after
impaired reabsorption or obstruction of CSF flow
(Hydrocephalus)

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 Cont.….

• If the patient develops clinical signs of increased intracranial

pressure, interventions to maintain cerebral perfusion include:
• Elevating the head of the bed to 30 degrees
• Inducing mild hyperventilation in the intubated patient
• Osmotic diuretics such as 25% mannitol or 3% saline
• Dexamethasone 0.25 -0.5mg/kg QID

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Monitoring and evaluation

• Assess the patient’s signs, symptoms, and risk factors for

meningitis.
• Perform ongoing surveillance for adverse drug reactions, drug
allergies, and drug interactions.
• Monitor the patient’s response to therapy (i.e., clinical
signs/symptoms and laboratory data), as well as the development
of complications, including seizures and hearing loss.

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Cont.…

• Evaluate whether the patient is a candidate for finishing out his or

her course of parenteral treatment on an outpatient basis.
• If so, the importance of close medical follow up and medication
compliance should be stressed to the patient and his or her family.

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Osteomyelitis
 Introduction
• Is an infection of the bone
• inflammatory process involving the bone and its structures
caused by pyogenic organisms that spread through the
bloodstream, fractures, or surgery
• The inflammatory response associated with acute osteomyelitis
can lead to bone necrosis and subsequently chronic infections

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Classification
• Based on route of infection
• Hematogenous Vs contiguous/direct inoculation
• Based on duration of the disease
• Acute (first episode or less than one week)
• Chronic (beyond 1 month or relapse or presence of
necrotic bone)

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Pathophysiology
• Bone can become infected:
• Via the presence of bacteria in the bloodstream,
• By direct inoculation from trauma or surgery
• By spread from an adjacent site (e.g., soft-tissue
infection).
• Microorganisms adhere to the bone and elicit an
inflammatory response
• Changes in vascular permeability (edema) and decreased
oxygen tension (ischemia)necrosis
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Type of Typical Age Site(s) Involved Risk Factors
Osteomyelitis (years)

Hematogenous Younger than Long bones and joints Prematurity, umbilical catheter or venous cut
1 down, respiratory distress syndrome, perinatal
asphyxia

1–20 Long bones (femur, tibia, Infection (pharyngitis, cellulitis, respiratory

humerus) infections), trauma, sickle cell disease, puncture
wounds to feet

Older than 50 Vertebrae Diabetes mellitus, blunt trauma to spine, urinary

tract infection

Contiguous without Older than 50 Femur, tibia, mandible Hip fractures, open fractures
Vascular
insufficiency

Contiguous with Older than 50 Feet, toes Diabetes mellitus, peripheral vascular disease,
Vascular pressure sores
insufficiency
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 Cont.…..
• Acute Hematogenous Osteomyelitis
• Single pathogen most often isolated
• S. aureus is the predominant pathogen
• Other pathogens based on risk factors:
• Neonates: E. coli or group B streptococci
• Elderly: E. coli [secondary to urinary tract infections
(UTIs)]
• Patients with diabetes and PVD : Polymicrobial
• Sickle cell patients: Salmonella
• Patients with prosthetic implants: Coagulase-negative
staphylococci
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• Contiguous Focus Osteomyelitis with Vascular Insufficiency
• Multiple pathogens often isolated
• Mixture of aerobic and anaerobic organisms:
• S. aureus, Enterococcus spp. Enterobacteriaceae, P.
aeruginosa
• Anaerobes

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• Contiguous Focus Osteomyelitis without Vascular Insufficiency
• Single or multiple pathogens isolated
• S. aureus is predominant pathogen
• Other pathogens based on source of infection:
• For example: Mandibular osteomyelitis (mixture of aerobic
and anaerobic oral flora)

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 Clinical presentation & Dx tests
• Systemic: Fever, chills, malaise
• Localized: Pain or tenderness, edema, erythema, inflammation, decreased
range of motion of infected area
• Non-specific inflammatory markers for infection include:
• WBC
• Erythrocyte sedimentation rate (ESR)--- measures how quickly red blood
cells settle to the bottom of a test tube.
• C reactive protein( CRP) may be elevated or within normal limits.
• CRP 0.3 to 1.0 mg/dL
• An elevated WBC is mostly seen in patients with acute osteomyelitis.
• CRP rises faster than ESR during early stages of infection.
• CRP returns to normal levels more quickly than ESR.
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• Imaging studies include:
• Plain film radiographs
• Most commonly used for initial screening
• Bone destruction is not apparent for 10 to 21 days following
infection
• Magnetic resonance imaging (MRI)
• Most accurate for diagnosing bone infection
• Can detect early infection
• More expensive than radiograph

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• Microbiologic evaluation:
• Bone biopsy can provide definitive diagnosis:
• Samples should be submitted for culture and histology
• Rarely performed due to invasive nature
• Blood cultures may be positive in patients with hematogenous
osteomyelitis
• Superficial swabs should have limited role in directing therapy
• May represent colonization rather than infecting organism(s)

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Management
• Goal of therapy
• To relieve sign and symptoms
• To eradicate the infection
• To prevent recurrence

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Cont.….
General Approach To Treatment
• Antimicrobial therapy alone is the mainstay of treatment for
acute osteomyelitis.
• Treatment for chronic osteomyelitis typically requires a
combination of antimicrobial therapy and surgical
intervention
• If the patient is not a candidate for surgical intervention,
prolonged antimicrobial therapy is generally necessary

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 Pharmacologic Therapy
• Empiric antimicrobial therapy should target likely causative
pathogen(s) based on patient-specific risk factors and route of
infection
• Empiric antimicrobial coverage against S. aureus should be
considered for all classifications of osteomyelitis.
• Specific recommendations may vary based on factors such as
patient allergies, potential for harboring a resistant organism,
institution formulary, and cost considerations.

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 Cont.….
• Typically, treatment is initiated with intravenous
antimicrobials
• to ensure that therapeutic drug concentrations will be
achieved in the bone.
• Following 1 to 2 weeks of intravenous therapy,
• a switch to oral antibiotics may be considered in patients
with good adherence and outpatient follow-up.

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 Cont.….

• The duration of treatment is typically 4 to 6 weeks for acute

osteomyelitis.
• Chronic osteomyelitis also requires 4 to 6 weeks of therapy;
• However, the total length of therapy should be counted after
the date of the last major surgical intervention
• Antibiotics used in the management of acute osteomyelitis
generally are given in high doses

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Cont.….
STG
• Vancomycin, 30mg/kg/day , IV , in two divided doses (initially 20
mg/kg loading dose, not to exceed 2 g/dose) + Ceftriaxone 2 g IV
every 24 hours OR Ciprofloxacin, 400 mg IV q12 hours or 750mg,
PO BID
• Alternative
• Cloxacillin, 2gm, I.V . QID +Ciprofloxacin, 400 mg IV q12 hours
or 750mg, PO BID

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 Empirical Treatment of Osteomyelitis
Patient Subtype Likely Infecting Organism Antibiotica

Newborn Staphylococcus aureus, streptococci, Nafcillin or oxacillin 50–150 mg/kg/day IV plus cefotaxime 100–
Escherichia coli 200 mg/kg/day IV

Children 5 years of age or If vaccinated for Haemophilus influenzae Nafcillin 150 mg/kg/day IV or cefazolin 100 mg/kg/day IV
younger type B: S. aureus or streptococci

If not vaccinated against H. influenzae type B Cefuroxime 150 mg/kg/day IV

Children older than 5 years of S. aureus Nafcillin 150 mg/kg/day IV or cefazolin 100 mg/kg/day IV
age

Adults S. aureus Nafcillin 2 g IV every 4 hours or cefazolin 2 g IV every 8 hours

IV drug abusers Pseudomonas Ciprofloxacin 750 mg PO twice daily or ceftazidime 2 g IV every 8

hours plus tobramycin 5 mg/kg/day IV

Postoperative or posttrauma Gram-positive and gram-negative organisms Nafcillin 2 g IV every 4 hours plus ceftazidime 2 g IV every 8 hours
patients or ticarcillin-clavulanate 3.1 g IV every 4 hours

Patients with vascular Gram-positive and gram-negative organisms Nafcillin 2 g IV every 4 hours or cefazolin 2 g IV every 8 hours plus
insufficiency ceftazidime 2 g IV every 8 hours

If anaerobes suspected Cefotetan 2 g IV every 12 hours or clindamycin 900 mg IV every 8

hours plus ceftazidime 2 g IV every 8 hours
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 Outcome Evaluation
• Therapeutic success is measured by the extent to which the care
plan:
• Resolves signs and symptoms (with in 48-72 hours)
• Normalizes of laboratory tests (WBC, CRP, and ESR) (with in
1 week)
• Eradicates the microorganism(s)
• Prevents relapses
• Prevents complications such as amputation.

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• If poor response is noted, the following should be evaluated:
• Patient compliance
• Appropriate dosage to achieve therapeutic concentrations
• Development of antimicrobial resistance
• Need for additional imaging studies
• Diagnostic re-evaluation.
• Due to high rates of relapse, patients should have medical
follow-up for at least 1 year following resolution of symptoms

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 Questions ?

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