Meningitisin Adults

Dr. Dino SgarabottoMalattie Infettive e TropicaliAzienda Ospedaliera di Padova

ACUTE CNS INFECTIONS

1.Bacterial meningitis***

2.Meningoencephalitis

3.Brain abscess

4.Subdural empyema

5.Epidural abscess

6.Septic venous sinus

thrombophlebitis

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

APPROACH TO THE PATIENT WITHSUSPECTED MENINGITIS

Decision-Making at 1-2 Hours

CSF Analysis

CSF smears/stainsCSF antigen screens

CSF “profile”

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

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.

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]

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

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

THE PATIENT WITH SUSPECTEDCNS INFECTIONContraindications 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

CNS INFECTIONSCCT

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

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

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

CNS INFECTIONSMRI

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

THE PATIENT WITH SUSPECTED CNS INFECTIONRole 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

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

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

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.

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

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

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

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

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

New Engl J Med 2006;354:44-53

New Engl J Med 2006;354:44-53

↑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

adjunctive dexamethasonetherapy 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

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.

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.

intensive care management

New Engl J Med 2006;354:44-53

decline in consciousness

New Engl J Med 2006;354:44-53

Lindvall P, et al Reducingintracranial pressure may increasesurvival 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

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

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.

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

New Engl J Med 2006;354:44-53

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

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

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

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