base harrisons 19 th edition

1. ACUTE BACTERIAL MENINGITIS
- DR. KIRAN BIKKAD

2. DEFINITION
• Bacterial meningitis is an acute purulent infection within the
subarachnoid space.
• It is associated with a CNS inflammatory reaction that may
result in decreased consciousness, seizures, raised intracranial
pressure (ICP), and stroke.
• The meninges, subarachnoid space, and brain parenchyma
are all frequently involved in the inflammatory reaction
(meningoencephalitis)

3. EPIDEMIOLOGY
• M/C suppurative CNS infection
• Annual incidence in the US >2.5 cases/100,000
population.
• M/C Organisms responsible are:-
1. Streptococcus pneumoniae(~50%)
2. Neisseria meningitidis(~25%)
3. Group B streptococci (~15%)
4. Listeria monocytogenes(~10%)
5. Haemophilus influenzae type b (<10%) of cases of
bacterial meningitis.
• N. meningitidis is causative organism for epidemics of
meningitis every 8 to 12 years.

4. ETIOLOGY
• S. pneumoniae
• M/C/C in adults >20 years of age
• Predisposing conditions:-
– pneumococcal pneumonia
– pneumococcal sinusitis or otitis media
– alcoholism, diabetes, splenectomy, hypogammaglobulinemia,
complement deficiency
– head trauma with basilar skull fracture and CSF rhinorrhea.
• The mortality rate ~20%

5. N. Meningitidis
• Incidence decreased d/t immunization with quadrivalent
(serogroups A, C, W-135, and Y) meningococcal
glycoconjugate vaccine.
• Presence of petechial or purpuric skin lesions - clue
• Initiated by nasopharyngeal colonization

6. Gram-negative bacilli
• Individuals with chronic & debilitating diseases
1. Diabetes
2. Cirrhosis
3. Alcoholism
4. Chronic UTI.
• Complicate neurosurgical procedure (associated with CSF
rhinorrhea or otorrhea)
1. Craniotomy
2. Head trauma
• Predisposing conditions : Otitis, mastoiditis, and sinusitis

7. • Meningitis complicating endocarditis d/t viridans
streptococci, S. aureus, Streptococcus bovis, HACEK group
(Haemophilus, Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, Kingella
kingae), or enterococci.
• Group B Streptococcus, or Strep. Agalactiae:- in individuals
>50 years
• S. aureus & CONS causes meningitis following invasive
neurosurgical procedures, particularly shunting procedures
for hydro-cephalus or intrathecal chemotherapy

8. • L. monocytogenes :-in neonates (<1 month of age), pregnant
women, individuals >60 years, and immuno-compromised Pts.
• Infected by foods contaminated by Listeria.
• E.g. coleslaw, milk, soft cheeses, ready-to-eat foods, meat &
hotdogs.

9. PATHOGENESIS

11. CLINICAL PRESENTATION
• Classic clinical triad :-
1. Fever
2. Headache
3. Nuchal rigidity
• Decreased level of consciousness: >75% of patients
• Fever & either headache/stiff neck/altered
consciousness in every patient
• Nausea, vomiting & photophobia

12. • Seizures occur as initial presentation in 20–40%.
1. Focal seizures d/t focal arterial ischemia or infarction,
cortical venous thrombosis with hemorrhage, or focal
edema.
2. Generalized seizure d/t hyponatremia, cerebral anoxia, or
toxic effects of antimicrobial agents.

13. • Raised ICP
• 90% patients will have CSF opening pressure >180 mmH2O.
• Signs of increased ICP :
– Deteriorating level of consciousness,
– Papilledema
– Dilated poorly reactive pupils
– 6th CN palsy
– Decerebrate posture
– Cushing reflex (bradycardia, hypertension, irregular respiration).
• Most disastrous complication of increased ICP is cerebral
herniation.

14. DIAGNOSIS
1. Blood culture
2. Examination of the CSF
3. Neuroimaging studies (CT or MRI) prior to LP
• Perform LP without prior neuroimaging
– Immuno-competent patient
– No h/o recent head trauma
– Normal level of consciousness &
– No evidence of papilledema / focal neurologic deficits

15. • The classic CSF abnormalities in bacterial meningitis
– (1) polymorphonuclear (PMN) leukocytosis (>100 cells/μL in 90%)
– (2) decreased glucose concentration (<2.2 mmol/L [<40 mg/dL] and/or
CSF/serum glucose ratio of <0.4 in ~60%)
– (3) increased protein concentration (>0.45 g/L [>45 mg/dL] in 90%
– (4) increased opening pressure (>180 mmH2O in 90%).
• CSF bacterial cultures are positive in >80% of patients &
• CSF Gram’s stain demonstrates organisms in >60%.

16. • The CSF glucose conc. is low when CSF/serum glucose ratio is
<0.6.
• A CSF/serum glucose ratio <0.4 is highly suggestive of
bacterial meningitis
• Also be seen in :-
– Fungal
– Tuberculosis &
– Carcinomatous meningitis.
• PCR that uses specific bacterial primers to detect the nucleic
acid of S. pneumoniae, N. meningitidis, Escherichia coli, L.
monocytogenes, H. influenzae, and S. agalactiae can be
obtained

17. • Latex agglutination (LA) test for the detects bacterial antigens
• The CSF LA test has a specificity of 95–100% for S. pneumoniae &
N. meningitidis & sensitivity of the CSF LA test 70–100% for detec-
tion of S. pneumoniae & 33–70% for detection of N. meningitidis
antigens, so a negative test does not exclude infection
• Limulus amebocyte lysate assay is a rapid diagnostic test for
detection of gram-negative endotoxin in CSF for diagnosis of gram-
negative bacterial meningitis.

18. • Neuroimaging studies :-
1. CT
2. MRI
• MRI is preferred over CT, b’coz superior in demonstrating cerebral
edema and ischemia.
• Diffuse meningeal enhancement, seen after administration of
gadolinium.
• Meningeal enhancement is not diagnostic of meningitis & occurs in
any CNS disease associated with increased blood-brain barrier
permeability.
• Petechial skin lesions : - meningococcemia

19. DIFFERENTIAL DIAGNOSIS
• 1.. Viral meningo-encephalitis
• Particularly HSV encephalitis
• HSV encephalitis presentation
– headache, fever, altered consciousness, focal neurologic deficits (e.g.
dysphasia, hemiparesis), and focal or generalized seizures.
• How to distinguish HSV encephalitis from bacterial
meningitis:-
• CSF studies
• Neuroimaging
• EEG

20. • The typical CSF of viral CNS infection
1. Lymphocytic pleocytosis
2. Normal glucose concentration
– (in contrast to PMN pleocytosis and hypoglycorrhachia characteristic of
bacterial meningitis)
• MRI abnormalities :-
1. Bacterial meningitis :- only meningeal enhancement in uncomplicated.
2. HSV encephalitis:- on T2-weighted, fluid-attenuated inversion recovery
(FLAIR) and diffusion-weighted MRI images, high signal intensity lesions in
orbito-frontal, anterior & medial temporal lobes in the majority of patients
within 48 h of symptom onset.
• In HSV encephalitis EEG have a distinctive periodic pattern.

21. Rickettsial disease (RMSF)
• Present with high fever, prostration, myalgia, headache, nausea,
vomiting
• Characteristic rash within 96 hrs.
• The rash is initially a diffuse erythematous maculopapular difficult
to distinguish from meningococcemia.
• It progresses to a petechial , then purpuric rash, and if untreated,
necrosis/gangrene.
• Rash typically begins in wrist, ankles & spreads distally &
proximally within few hours.
• Diagnosis by immunofluorescent staining of skin biopsy specimens.

22. Ehrlichioses
• Trans-mitted by tick.
• The clinical & laboratory manifestations of infections are
similar.
• Patients present with:- fever, headache, confusion, nausea,
and vomiting.
• Laboratory :-
– Decreased RBC, WBC, Platelet.
– Elevations in LDH, ALP, LDH.
• MRI done if:- features of FND.
– To detect the intracranial infection
– To search for associated areas of infection in sinuses or mastoid.

23. Non infectious CNS disorders
1. SAH
2. Chemical meningitis
1. d/t rupture of tumor contents into the CSF
2. (e.g., from a cystic glioma or craniopharyngioma epidermoid or
dermoid cyst)
3. Drug-induced hypersensitivity meningitis
4. Carcinomatous/lymphomatous meningitis
5. Meningitis with inflammatory disorders
1. E.g. sarcoid, SLE, Behçet’s syndrome, pituitary apoplexy,
uveomeningitic syndromes (Vogt-Koyanagi-Harada syndrome).
6. Subacute meningitis
1. E.g. Mycobacterium tuberculosis, Cryptococcus neoformans,
Histoplasma capsulatum, Coccidioides immitis, Treponema pallidum.

24. TREATMENT
• EMPIRICAL ANTIMICROBIAL THERAPY
• Medical emergency
• Goal : to begin antibiotic therapy within 60 min
• Empirical antimicrobial therapy should include a
combination of
1. Dexamethasone
2. 3rd/4th -generation cephalosporin (e.g., ceftriaxone, cefotaxime, or
cefepime)
3. Vancomycin +
4. Acyclovir (as HSV encephalitis is leading D/D) &
5. Doxycycline (during tick season)

25. • Ceftriaxone or cefotaxime :- coverage for susceptible S. pneumoniae,
group B streptococci, and H. Influenzae & N. meningitidis.
• Cefepime 4th-gen cephalosporin with greater activity against
Enterobacter & Pseudomonas aeruginosa.
• Ampicillin added to empirical regimen for coverage of L. monocytogenes
– in <3 months of age & >55yrs or those with impaired cell-mediated immunity
• Metronidazole :- for gram-negative anaerobes in otitis, sinusitis, or
mastoiditis.
• Hospital-acquired meningitis, following neurosurgical procedures:-
vancomycin + ceftazidime/cefepime/meropenem.
• Meropenem : carbapenem antibiotic, highly active against L.
monocytogenes, P. aeruginosa, and penicillin-resistant pneumococci.

26. SPECIFIC ANTIMICROBIAL THERAPY
• Meningococcal Meningitis
• penicillin G - antibiotic of choice (in sensitive cases)
• CSF isolates of N. meningitidis tested for penicillin and ampicillin susceptibility
• if resistance :- Rx- cefotaxim/ceftriaxone
• A 7-day course of i.v. antibiotic - adequate for uncomplicated meningococcal
meningitis.
• Chemoprophylaxis :-
• For index case & close contacts
• 2-day regimen of rifampin (600 mg, 12 hrly x 2 days in adults & 10 mg/kg 12 hrly
for 2 days in children >1 year).
• Rifampin:- not recommended in pregnant women.
• Alternative, azithromycin (500 mg) one dose or one i.m. ceftriaxone (250 mg).
– Close contacts definition : individuals who had contact with oropharyngeal secretions, through
kissing, sharing toys, beverages or cigarette

27. Pneumococcal Meningitis
• A cephalosporin (ceftriaxone, cefotaxime or cefepime) and vancomycin.
• All CSF isolates tested for sensitivity , therapy modified accordingly
• An isolate of S. pneumoniaeis considered to be
• susceptible to penicillin with a MIC <0.06 μg/mL
• Resistant when MIC is >0.12 μg/mL.
• cephalosporin MICs ≤0.5 μg/mL are considered sensitive to the
cephalosporins
• Those with MICs of 1 μg/mL - intermediate resistance
• MICs ≥2 μg/mL - resistant.
• For MIC >1 μg/mL, vancomycin is antibiotic of choice.

28. • Rifampin can be added to vancomycin for its synergistic effect
• Resistance develops rapidly when it is used alone.
• 2-week course of i.v. antimicrobial therapy is recommended
• Repeat LP : 24–36 h after the initiation of antimicrobial therapy to
document sterilization of CSF.
• Failure to sterilize the CSF after 24–36 h of therapy consider evidence of
antibiotic resistance.
• The intraventricular route of administration is preferred over the
intrathecal route because adequate concentrations of vancomycin in the
cerebral ventricles are not always achieved with intrathecal
administration

29. Listeria Meningitis
L. Monocytogenesis
• Ampicillin for at least 3 weeks
• Gentamicin is added (critically ill patients)
2 mg/kg loading dose
7.5 mg/kg/day, 8 hrly -adjusted for renal function
• Alternative (penicillin-allergics)
– Trimethoprim (10–20 mg/kg per day) & sulfa-methoxazole (50–100
mg/kg per day) given every 6 h.

30. Staphylococcal Meningitis
• Meningitis due to susceptible strains of S. aureus or
coagulase-negative staphylococci is treated with Nafcillin
• Vancomycin is DOC for MRSA & penicillin allergics.
• If the CSF is not sterilized after 48 h of i.v. vancomycin, then
either intraventricular or intrathecal vancomycin, 20 mg once
daily

31. Gram-Negative Bacillary Meningitis
• 3rd gen cephalosporins—
• cefotaxime, ceftriaxone, and ceftazidime
• Exception:- P. aeruginosa (treated with
ceftazidime/cefepime/meropenem)
• 3-week i.v. antibiotic therapy recommended

32. ADJUNCTIVE THERAPY
• Release of bacterial cell-wall components by bactericidal antibiotics l/t
production of inflammatory cytokines (IL-1β and TNF-α) in subarachnoid
space.
• Dexamethasone exerts beneficial effect by inhibiting synthesis of IL-1β
and TNF-α at level of mRNA, decreasing CSF outflow resistance,
stabilizing BBB.
• Giving dexa 20 min before antibiotic therapy :- inhibits production of TNF-
α by macrophages and microglia only if administered before cells are
activated by endotoxin.

33. • Dexa 10 mg i.v. , 15–20 min before first dose of antimicrobial agent &
repeated every 6 h for 4 days.
• Dexa may decrease the penetration of vancomycin into CSF & delays the
sterilization of CSF in experimental models of S. pneumoniae
• As a result, to assure reliable penetration of vancomycin into the CSF,
vancomycin dose of 45–60 mg/kg/day.
• Alternatively, vancomycin given by intra-ventricular route.

34. INCREASED INTRACRANIAL PRESSURE
• Emergency treatment :
1. Elevation of Pts head to 30–45°
2. Intubation and hyperventilation (PaCO2:- 25–30 mmHg)
3. Mannitol
4. Should be managed in ICU with accurate ICP measurement.

35. PROGNOSIS
• Mortality rate :-
– 3–7% for meningitis caused by H. influenzae, N. meningitidis, or group
B streptococci
– 15% for that due to L. monocy-togenes
– 20% for S. pneumoniae
• Decreased CSF glucose concentration <40 mg/dL] and
markedly increased CSF protein concentration (>3 g/L [> 300
mg/dL]) predictive of increased mortality and poorer
outcomes

36. Risk of death
• Increases with:
– (1) Decreased level of consciousness on admission
– (2) Onset of seizures within 24 h of admission
– (3) Signs of increased ICP
– (4) Infancy and age >50
– (5) Presence of comorbid conditions including shock
and/or mechanical ventilation
– (6) Delay in the initiation of treatment.

37. Common Sequelae
• Decreased intellectual function
• Memory impairment
• Seizures
• Hearing loss
• Dizziness
• Gait disturbances.

40. THANK YOU