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

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

2. 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

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

4. Routes of Entry • Hematogenous • Neighboring focus • Anatomic defect • congenital • traumatic • surgical • Intraneural pathways

5. 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

6. 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 Base Making Process For Decision-Making Within the 1st 30 mins Clinical assessment of patient contact After 1-2 hours CSF analysis At 24-48 hours CSF cultures Thereafter as clinically indicated

7. 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

8. 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

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

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

12. 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

15. 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

16. CEREBROSPINAL FLUID PROFILES Neutrophilic/Low glucose (purulent) Lymphocytic/Normal glucose Lymphocytic/Low glucose

17. 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

18. 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

19. 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

20. 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

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

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

24. 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)

25. Predisposing Factor Age 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 meningitidis H. influenzae, N. meningitidis, S. pneumoniae S. pneumoniae, N. meningitidis S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS

26. 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%

27. 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 COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS

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

29. EMPIRIC THERAPY OF MENINGITIS IN THE ADULT Clinical SettingLikely PathogensTherapy 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

30. 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

32. 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 VIRAL MENINGITIS/ENCEPHALITIS

33. 37 y/male Headache, spontaneous tendency to sleep, Mental changes: unrecognising time and location, Dx?

34. 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

35. Cryptococcosis

36. Toxoplasmosis

38. 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

39. Multiple abscesses in a 6-year- old child

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

41. Later Cerebritic / Early Abscess Stage – increasing necrosis of center with beginnings of capsule formation

42. Mature abscess (Late Stage) - dense fibro-gliotic capsular wall and purulent center

43. 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

44. Discitis with local osteomyelitis and epidural empyema