Acute meningitis

1. Meningitis
in Adults
Dr. Dino Sgarabotto
Malattie Infettive e Tropicali
Azienda Ospedaliera di Padova

2. ACUTE CNS INFECTIONS
1.Bacterial meningitis***
2.Meningoencephalitis
3.Brain abscess
4.Subdural empyema
5.Epidural abscess
6.Septic venous sinus
thrombophlebitis

3. APPROACH TO THE PATIENT WITH SUSPECTED
MENINGITIS
Decision-Making Within the First 30 Minutes
Clinical Assessment
Mode of presentation
Acute (< 24 hrs)
Subacute (< 7 days)
Chronic (> 4 wks)
Historical/physical exam clues
Clinical status of the patient
Integrity of host defenses

4. APPROACH TO THE PATIENT WITH
SUSPECTED MENINGITIS
Decision-Making at 1-2 Hours
CSF Analysis
CSF smears/stains
CSF antigen screens
CSF “profile”

5. CSF SMEARS & STAINS
GmS + in 60-90% of pts with
untreated bacterial meningitis
With prior ATB Rx, positivity of
GmS decreases to 40-60%
REMEMBER: + GmS = Heavy
organism burden & worse
prognosis

6. CEREBROSPINAL FLUID PROFILES*
Neutrophilic/Low glucose (purulent)
Lymphocytic/Normal glucose
Lymphocytic/Low glucose
*Profile designation based on WBC differential and
glucose concentration.
NE Hyslop, Jr and MN Swartz, Postgrad Med 58:120, 1975.

7. BACTERIAL VS VIRAL MENINGITIS
Predictors of bacterial etiology:
CSF glucose < 34
CSF: Serum glucose ratio < 0.23
CSF protein > 220
CSF WBC count > 2000
CSF neutrophil count > 1180
[Presence of any ONE of the above findings predicts bacterial
etiology with > 99% certainty]

8. APPROACH TO THE PATIENT
WITH SUSPECTED MENINGITIS
Decision-Making at 24-48 hours
CSF Culture Results
Culture positive ® Adjust therapy based
upon specific organism and sensitivities
Culture negative ® Evaluate for “aseptic”
meningitis syndrome

9. TO LP OR NOT TO LP
Single most impt diagnostic
test
Mandatory, esp if bacterial
meningitis suspected
If LP contraindicated, obtain
BCs (+ in 50-60%), then begin
empirical Rx

10. THE PATIENT WITH SUSPECTED
CNS INFECTION
Contraindications to LP
Absolute:Skin infection over site
Papilledema, focal neuro signs, ↓MS
Relative:Increased ICP without papilledema
Suspicion of mass lesion
Spinal cord tumor
Spinal epidural abscess
Bleeding diathesis or ↓ plts

11. CNS INFECTIONS
CCT
Over-employed diagnostic modality ®
Leads to unnecessary delays in Rx & added
cost
Rarely indicated in pt with suspected acute
meningitis
Mandatory in pt with possible focal infection
Increased sensitivity with contrast
enhancement

12. CCT Before LP in Patients with
Suspected Meningitis
301 pts with suspected meningitis; 235
(78%) had CCT prior to LP
CCT abnormal in 56/235 (24%); 11 pts
(5%) had evidence of mass effect
Features associated with abnl CCT
were age >60, immunocompromise, H/
O CNS dz, H/O seizure w/in 7d, &
selected neuro abnls
Hasbun, NEJM 2001;345:1727

13. CCT Before LP
(Cont.)
Neuro abnls included altered MS, inability to
answer 2 consecutive questions or follow 2
consecutive commands, gaze palsy, abnl visual
fields, facial palsy, arm or leg drift, & abnl
language
96/235 pts (41%) who underwent CCT had none
of features present at baseline
CCT normal in 93 of these 96 pts (NPV 97%)
Hasbun, NEJM 2001;345:1727

14. CNS INFECTIONS
MRI
Not generally useful in acute
diagnosis (Pt cooperation; logistics)
Very helpful in investigating
potential complications developing
later in clinical course such as
venous sinus thrombosis or
subdural empyema

15. THE PATIENT WITH SUSPECTED CNS
INFECTION
Role of Repetitive LP’s
1. Rarely indicated in proven bacterial meningitis
unless clinical response not optimal or as
expected, fever recurs, or infection is due to ATB
resistant pathogen
2.Essential in pts with “aseptic meningitis”
syndromes to monitor course &/or response to
empiric therapies
3.Essential in pts with subacute/chronic meningitis
of proven etiology to assess response to Rx
4.Not routinely indicated at end-of-therapy for
bacterial meningitis

19. Skin rashes
Is due to small skin bleed
All parts of the body are affeced
The rashes do not fade under pressure
Pathogenesis:
a. Septicemia
b. wide spread endothelial damage
c. activation of coagulation
d. thrombosis and platelets aggregation
e. reduction of platelets (consumption )
f. BLEEDING 1. skin rashes
2. adrenal hemorrhage
Adrenal hemorrhage is called Waterhouse-Friderichsen Syndrome.
It cause acute adrenal insufficiency and is usually fatal

20. Bacterial meningitis → annual incidence of
4~6 cases per 100,000 adults (defined as
patients older than 16 years of age), and
Strep. pneumoniae and. meningitidis are
responsible for 80 percent of all cases
New Engl J Med 2006;354:44-53

21. initial approach
classic triad of fever, neck stiffness, and altered mental
status → 44%
almost all with at least 2 of 4 symptoms — headache,
fever, neck stiffness, and altered mental status (GCS<
14)
Lumbar puncture is mandatory BUT…
expanding masses (e.g., subdural empyema, brain
abscess, or necrotic temporal lobe in herpes simplex
encephalitis) may MIMICS bacterial meningitis, lumbar
puncture may be complicated by brain herniation.

22. prospective study involving 301adults with
suspected meningitis confirmed that
clinical features can be used to identify
patients who are unlikely to have
abnormal findings on cranial CT (41
percent of the patients in this study), 235
patients who underwent cranial CT, in only
5 patients (2 percent) was bacterial
meningitis confirmed -------------------- Hasbun R
et. Compute tomography of the head before lumbar puncture in adults with suspected
meningitis. N Engl J Med 2001;345:1727-33

23. CT should precede lumbar puncture → new-
onset seizures,immunocompromised state, signs
that are suspicious for space-occupying lesions,
or moderate-to-severe impairment of
consciousness----- 45%
probable bacterial meningitis but neuroimaging
is not available → lumbar puncture should be
DONE in moderate-to-severe impairment of
consciousness or in immunocompromised state.
But new-onset seizure, papilledema, or evolving
signs of brain tissue shift →DEFER lumbar
puncture

24. The median delay between time of arrival at ER
and administration of antibiotics was 4 hours
an association between delays in administering
antibiotics longer than 6 hours after arrival in
ER and death -----Proulx N etc. Delays in the administration of antibiotics are
associated with mortality from adult acute bacterial meningitis. QJM 2005;98:291-8
Antibiotics should be given as soon as possible, even before CT
and LP done

25. 40 % had very high opening pressures (>400 mm, water
manometer) → lower levels of consciousness but not
with adverse outcome
pleocytosis (100 to 10,000 white cells per cubic
millimeter), ↑protein levels (>50 mg per deciliter [0.5 g
per liter]), ↓CSF glucose levels (<40 percent of
simultaneously measured serum glucose) are usually
present
predominance of neutrophils (range, 80 to 95 percent) in
CSF, but a predominance of lymphocytes can occur
Normal or marginally ↑CSF WBC → 5 to 10 % and are
associated with an adverse outcome

26. Gram’s staining (sensitivity 60 to 90%;
specificity ≥97 %), ANTIGEN test, PCR

27. New Engl J Med 2006;354:44-53

28. New Engl J Med 2006;354:44-53

29. ↑penicillin-resistant pneumococci, combination
therapy with vancomycin plus a third generation
cephalosporin (either ceftriaxone or cefotaxime)
→standard empirical antimicrobial therapy…
( some favors to add another rifampin )…..
should also receive adjunctive dexamethasone
therapy
Respiratory isolation for 24 hours is indicated for
suspected meningococcal infection

30. adjunctive dexamethasone
therapy
a prospective, randomized, double-blind, multicenter trial
of adjuvant treatment with dexamethasone, as compared
with placebo, in adults →Dexamethasone (10 mg) or
placebo was administered 15 to 20 minutes before or
with the first dose of antibiotic and q6h for 4 days-----total
of 301 ( 157 dexamethason and 144 placebo ) →
dexamethasone with ↓risk of unfavorable outcome from
25% to 15% (number needed to treat, 10 patients). ↓
Mortality from 15 %to 7 %---Greatest benefit with
intermediate disease severity( GCS8~11) and with
pneumococcal meningitis (unfavorable outcomes in 26
%of the dexamethasone group, as placebo with 52%,
mortality ↓from 34 % to 14 %.--------------de Gans J, van de Beek D.
Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-56

31. dexamethasone should be continued for 4
days in patients with bacterial meningitis,
regardless of microbial cause or clinical
severity
discontinue dexamethasone if the
meningitis is found to be caused by a
bacterium other than S. pneumoniae
-----Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis 2004;39:1267-84.

32. Starting corticosteroids before or with the
first dose of parenteral antimicrobial
therapy appears to be more effective than
starting corticosteroids after the first dose
of antimicrobial therapy----van de Beek D, de Gans J, McIntyre
P, Prasad K. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev
2003;3:CD004305.

33. intensive care management
New Engl J Med 2006;354:44-53

34. decline in consciousness
New Engl J Med 2006;354:44-53

35. Lindvall P, et al Reducing
intracranial pressure may increase
survival among patients with bacterial meningitis Clin Infect Dis 2004;38:384-90
↓ICP with use of an unconventional volume-targeted
(“Lund concept”) ICP management protocol.
mean ICP was significantly higher and cerebral
perfusion pressure was markedly decreased in patients
who did not survive (in spite of treatment).
Lund Concept → antihypertensive therapy (beta1-
antagonist,alpha2-agonist), normalization of the plasma
colloid osmotic pressure and the blood volume, and
antistress therapy

36. seizures or a clinical suspicion of prior
seizure should receive anticonvulsant
therapy, but the low incidence of this
complication does not justify prophylaxis.
Brain EEG--- to R/O nonconvulsive status
epilepticus with conscious disturbance
Repeated lumbar puncture or placement
of temporary lumbar drain may effectively
reduce ICP; performing a ventriculostomy
may also be considered

37. focal neurologic abnormalities
cerebral venous thrombophlebitis should be
considered in patients with deterioration of
consciousness, seizures, fluctuating focal
neurologic abnormalities, and stroke with
nonarterial distribution
MRI with venous-phase studies confirms the
diagnosis. Treatment of cerebral
thrombophlebitis in bacterial meningitis is
directed toward the infection.

38. rapid deterioration→ think subdural
empyema → Clues : sinusitis and
mastoiditis (and recent surgery for either
of these Disorders) and recent head injury
 most frequent cranial-nerve abnormality is
involvement of 8th cranial nerve, which is
reflected in a hearing loss in 14 percent of
patients

39. New Engl J Med 2006;354:44-53

40. repeated lumbar puncture
in condition has not responded clinically after 48 H of
appropriate antimicrobial therapy
especially essential in treatment with pneumococcal
meningitis caused by penicillin-resistant or
cephalosporin-resistant strains and who receive
adjunctive dexamethasone therapy and vancomycin( c0z
decadron reduce BBB permeability)
Gram’s staining and culture of CSF should be negative
after 24 hours of appropriate antimicrobial therapy

41. outcome
Community-acquired meningitis caused by S.
pneumoniae has high fatality rates→19 to 37 %,
meningococcal meningitis are lower with fatality
rates of 3 to 13 %, morbidity rates of 3 to 7 %
In up to 30 % of survivors have long-term
neurologic sequelae
Before using Dexamethasone and afterusing
it----- expect ↓both morbidity and mortality

42. strongest risk factors for an unfavorable
outcome → systemic compromise, impaired
consciousness, low WBC in CSF, and infection
with S. pneumoniae.
cognitive impairment was detected in 27 % of
adults who had a good recovery from
pneumococcal meningitis. Cognitive impairment
consisted mainly of cognitive slowness, which
was related to lower scores on questionnaires
measuring the quality of life

43. future directions
role of oxygen–glucose deprivation of
hippocampal neurons as a complication of
meningitis, the role of cytokines, and the
protective roles of nuclear factor-κB1 and brain-
derived neurotrophic factor→ All promising but
unlikely be studied in controlled trials
Vaccines →approval in 2005 of a conjugate
meningococcal vaccine against serogroups A, C,
Y, and W135