Acute Meningitis Reşat ÖZARAS, MD, Prof. Infection Dept.

CNS INFECTIONS Overview l Life-threatening problems with –High mortality –High morbidity l Presentation –acute, –subacute, –chronic l Clinical findings determined by anatomic site(s) of involvement, infecting pathogen, and host response

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

Acute Meningitis

THE PATIENT WITH ACUTE CNS INFECTION Overall 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 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 l Fever l Headache l Nuchal rigidity l Altered mental status l Photophobia l Non-specific symptoms/signs l Focal neurological signs l Seizures l Specific clinical stigmata according to etiological agent l Children / elderly

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

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

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

CSF ANTIGEN SCREENS l Bacterial antigen screens detect S. pneumoniae, N. meningitidis, Hib; + in % of pts (esp. useful in pts with prior ATB Rx) l Crypto antigen screen detects C. neoformans; + in 90-95% of pts with crypto meningitis l 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 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 l Single most impt diagnostic test l Mandatory, esp if bacterial meningitis suspected l If LP contraindicated, obtain BCs (+ in 50-60%), then begin empirical Rx

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

CNS INFECTIONS CT l Over-employed diagnostic modality  Leads to unnecessary delays in Rx & added cost l Rarely indicated in pt with suspected acute meningitis l Mandatory in pt with possible focal infection l Increased sensitivity with contrast enhancement

THE THERAPY OF MENINGITIS Desirable Antimicrobic Properties 1.Activity vs suspected pathogen(s) [preferably cidal] 2.Adequate CSF diffusion 3.Acceptable risk of toxicity

THE THERAPY OF MENINGITIS CNS Penetration Good Diffusion Penicillins 3 rd & 4th Gen Cephs Chloramphenicol Rifampin TSX Poor Diffusion Early Gen Cephs Clindamycin AMGs Tetracyclines Macrolides

Bacterial Meningitis Important Changes in Epidemiology l Marked decline in the occurrence of Hib l ↑’ing incidence of S. pneumo (50+% of cases in US) l Shift from peds disease to adult disease l ↑’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 Factor Age 0-4 wk 4-12 wk 3 mo to 18 yr 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 meningitidis H. influenzae, N. meningitidis, S. pneumoniae S. pneumoniae, N. meningitidis S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli

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

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT Clinical SettingLikely Pathogens Therapy Community-acquiredS. pneumoniae Ceftriaxone N. meningitidis 2 gm q12h [Listeria] + [H. influenzae] Ampicillin 2 gm q4h Closed head traumaS. pneumoniae Pen G 3-4 mu q4h Streptococci + Vancomycin 1-2 gm q12h

Role of Steroids l The addition of anti-inflammatory agents has been attempted as an adjuvant in the treatment of meningitis l 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 l Less bilateral deafness late neurological sequelae in controls compared to children treated with steroids

Community-acquiredS. pneumoniae Ceftriaxone N. meningitidis 2 gm q12h [Listeria] + [H. influenzae] Ampicillin 2 gm q4h + Dexamethasone

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

NONVIRAL CAUSES OF ENCEPHALOMYELITIS Rocky Mountain spotted feverAcanthamoeba TyphusToxoplasma MycoplasmaPlasmodium falciparum BrucellosisTrypanosomiasis Subacute bacterial endocarditisWhipple’s disease Syphilis (meningovascular)Behcet’s disease Relapsing feverVasculitis Lyme disease Leptospirosis Tuberculosis Cryptococcus Histoplasma Naegleria

Cryptococcosis

Toxoplasmosis