CNS INFECTIONS Reşat ÖZARAS, MD , Ass. Prof. Infection Dept. rozaras@yahoo

CNS

INFECTIONS

Reşat ÖZARAS, MD, Ass. Prof.

Infection Dept.

[email protected]

CNS INFECTIONSOverview

Life-threatening problems with high associated mortality and morbidity

Presentation may be acute, subacute, or chronic Clinical findings determined by anatomic site(s) of

involvement, infecting pathogen, and host response Vulnerability of CNS to effects of inflammation &

edema mandates prompt diagnosis with appropriate therapy if consequences to be minimized

ACUTE CNS INFECTIONS

1. Bacterial meningitis***

2. Meningoencephalitis

3. Brain abscess

4. Subdural empyema

5. Epidural abscess

6. Septic venous sinus

thrombophlebitis

Routes of Entry

– Hematogenous

– Neighboring focus

– Anatomic defect

• congenital

• traumatic

• surgical

– Intraneural pathways

THE PATIENT WITH ACUTE CNS INFECTIONOverall Goals in Management

1. To promptly recognize the patient with an acute CNS infection syndrome

2. To rapidly initiate appropriate empiric therapy

3. To rapidly and specifically identify the etiologic agent, adjusting therapies as indicated

4. To optimize management of complicating features

APPROACH TO THE PATIENT WITH POSSIBLE CNS INFECTION

If the patient has a CNS infection syndrome, is it antimicrobial

or non-antimicrobial requiring?

Crucial and recurring question addressed sequentially over time

Points in Decision- Available Data BaseMaking Process For Decision-Making

Within the 1st 30 mins Clinical assessment of patient contact

After 1-2 hours CSF analysisAt 24-48 hours CSF cultures

Thereafter as clinically indicated

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

Clinical Features Fever Headache Nuchal rigidity Altered mental status Photophobia Non-specific symptoms/signs Focal neurological signs Seizures Specific clinical stigmata according to etiological agent Children / elderly

CSF STUDIES

Color/Clarity Cell counts/WBC diff Chemistries (protein, glucose) Stains/Smears (Gram) Cultures (routine) +/- Antigen screens

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

CSF ANTIGEN SCREENS

Bacterial antigen screens detect

S. pneumoniae, N. meningitidis, Hib; + in 50-100% of pts (esp. useful in pts with prior ATB Rx)

Crypto antigen screen detects C. neoformans; + in 90-95% of pts with crypto meningitis

Should NOT be a ordered routinely

CEREBROSPINAL FLUID PROFILES

Neutrophilic/Low glucose (purulent)

Lymphocytic/Normal glucose

Lymphocytic/Low glucose

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 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

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

THE THERAPY OF MENINGITISDesirable Antimicrobic Properties

1. Activity vs suspected pathogen(s)

[preferably cidal]

2. Adequate CSF diffusion

3. Acceptable risk of toxicity

THE THERAPY OF MENINGITISCNS Penetration

Good Diffusion

Penicillins

3rd& 4th Gen Cephs

Chloramphenicol

Rifampin

TSX

Poor Diffusion

Early Gen Cephs

Clindamycin

AMGs

Tetracyclines

Macrolides

Bacterial MeningitisImportant Changes in Epidemiology

Marked decline in the occurrence of Hib ↑’ing incidence of S. pneumo (50+% of

cases in US) Shift from peds disease to adult disease ↑’ing incidence of ATB-resistant

organisms, esp. S. pneumo– PCN resistance ~ 35% (15-20% high level)– Ceph resistance 15-20% (5-10% high level)

COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS

Predisposing FactorAge 0-4 wk

4-12 wk

3 mo to 18 yr 18-50 yr >50 yr

Common Bacterial Pathogens

Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella pneumoniae, Enterococcus spp., Salmonella

spp.S. agalactiae, E. coli, L. monocytogenes, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidisH. influenzae, N. meningitidis, S. pneumoniaeS. pneumoniae, N. meningitidisS. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli

Etiology - in Adults

S. pneumoniae 30-50% N. meningitidis 10-35% H. influenzae 1-3% G -ve bacilli 1-10% Listeria species 5% Streptococci 5% Staphylococci 5-15%

COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS

Predisposing Factor

Immunocompromised state

Basilar skull fracture

Head trauma; postneurosurgery

Cerebrospinal fluid shunt

Common Bacterial Pathogens

S. pneumoniae, N. meningitidis, L.

monocytogenes, aerobic gram-negative bacilli (including P. aeruginosa)

S. pneumoniae, H. influenzae, group A β-

hemolytic streptococci

Staphylococcus aureus, Staphylococcus

epidermidis, aerobic gram-negative bacilli

(including P. aeruginosa)

S. epidermidis, S. aureus, aerobic gram- negative bacilli (including P. aeruginosa),

P. acnes

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

Clinical Setting Likely Pathogens Therapy

Community-acquired S. pneumoniae CeftriaxoneN. meningitidis 2 gm q12h[Listeria] +[H. influenzae] Ampicillin 2 gm

q4h

Closed head trauma S. pneumoniae Pen G 3-4 mu q4hStreptococci +

Vancomycin 1-2 gm q12h

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

Clinical Setting Likely Pathogens Therapy

High risk patients S. aureus Vancomycin 2-3 gm/d Compromised hosts Gram negative + Neurosurgical bacilli Ceftazidime 2 gm q8h or Open head injury Listeria Cefepime 2 gm q8h Nosocomial [Ceftriaxone 2 gm q12h] Elderly [Cefotaxime 2 gm q4h] +/-

Ampicillin 2 gm q4h

Role of Steroids The addition of anti-inflammatory agents has been attempted

as an adjuvant in the treatment of meningitis

Early administration of corticosteroids for pediatric meningitis has shown no survival advantage, but there is a reduction in the incidence of severe neurologic complications and deafness

Less bilateral deafness late neurological sequelae in controls compared to children treated with steroids

VIRAL MENINGITIS/ENCEPHALITIS

Enteroviruses

Polioviruses

Coxsackieviruses

Echoviruses

Togaviruses Eastern equine

Western equine

Venezuelan equine

St. Louis

Powasson

California

West Nile

Herpesviruses

Herpes simplex

Varicella-zoster

Epstein Barr

Cytomegalovirus

Myxo/paramyxoviruses Influenza/parainfluenzae

Mumps

Measles

Miscellaneous Adenoviruses

LCM

Rabies

HIV

37 y/maleHeadache, spontaneous tendency to sleep, Mental changes: unrecognising time and location, Dx?

NONVIRAL CAUSES OF ENCEPHALOMYELITIS

Rocky Mountain spotted fever Acanthamoeba

Typhus Toxoplasma

Mycoplasma Plasmodium falciparum

Brucellosis Trypanosomiasis

Subacute bacterial endocarditis Whipple’s disease

Syphilis (meningovascular) Behcet’s disease

Relapsing fever Vasculitis

Lyme disease

Leptospirosis

Tuberculosis

Cryptococcus

Histoplasma

Naegleria

Cryptococcosis

Toxoplasmosis

BRAIN ABSCESS Infrequent but not uncommon; pathogenesis diverse with

contiguous spread & blood-borne seeding most common Clinical features include HA (90%), fever (57%), MS changes

(67%), hemiparesis (61%), & papilledema (56%) Dx often suggested by neuroimaging (CT or MRI) LP is contraindicated due to risk of herniation Infxns often polymicrobial (strep, enteric GNRs, &/or

anaerobes); S. aureus may cause abscesses in association with IE

Other less common etiologies include Nocardia, fungi, M. tuberculosis, T. gondii, & neurocysticercosis

Drainage often a necessary component of management

Multiple abscesses in a 6-year- old child

Early Abscess (Cerebritis) – Poorly Early Abscess (Cerebritis) – Poorly localized area of discoloration and localized area of discoloration and

softening. softening.

Later Cerebritic / Early Abscess Stage – increasing necrosis of center with beginnings of

capsule formation

Mature abscess (Late Stage) - dense fibro-gliotic capsular wall

and purulent center

BRAIN ABSCESSEmpiric Therapy

Penicillin G 18-24 mu IV qd

Metronidazole 500 mg IV q6h

Add nafcillin 12 gm/d if staph suspected

(use vanc if MRSA a concern) Add cefotaxime, ceftriaxone, or ceftazidime if GNRs

suspected Substitute vanc 2-4 gm IV/d for pen G if DRSP

suspected

Discitis with local osteomyelitis and epidural empyema