ACUTE

1

• ACUTE
• CNS
• INFECTIONS

2

• The precise and intelligent recognition and
  appreciation of minor differences is the real
  essential factor in all successful medical
  diagnosisEyes and ears which can see and hear,
  memory to record at once and to recall at
  pleasure the impressions of the senses, and an
  imagination capable of weaving a theory or
  piecing together a broken chain or unraveling a
  tangled clue, such are the implements of his
  trade to a successful diagnostician.
• Joseph Bell

3
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

4
ACUTE CNS INFECTIONS

• 1. Bacterial meningitis
• 2. Meningoencephalitis
• 3. Brain abscess
• 4. Subdural empyema
• 5. Epidural abscess
• 6. Septic venous sinus
• thrombophlebitis

5
THE PATIENT WITH ACUTE CNS INFECTIONOverall
Goals in Management

• 1. To quickly recognize patients with acute CNS
• infection syndromes
• 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
Does the patient have a CNS infection syndrome?

• Prodromal/concurrent URI sxs
• Fever, HA, altered MS
• Compatible PE findings
• - Meningismus - Active RT infxn
• - Exanthems - Focal neuro signs

7
If the patient has a CNS infection syndrome, is
it antimicrobial requiring?

• Untreated/partially Rxed bacterial meningitis
• Parameningeal suppurative foci
• M. tuberculosis/Fungi
• Syphilis/Borrelia/Rickettsia
• HSV/CMV/VZV
• Others (amebae, parasites, etc)

8
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

9
APPROACH TO THE PATIENT WITH SUSPECTED MENINGITIS

• Decision-Making Within the First 30 Minutes
• Clinical Assessment
• Mode of presentation
• Acute (lt 24 hrs)
• Subacute (lt 7 days)
• Chronic (gt 4 wks)
• Historical/physical exam clues
• Clinical status of the patient
• Integrity of host defenses

10
(No Transcript)
11
CSF STUDIES

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

12
APPROACH TO THE PATIENT WITHSUSPECTED MENINGITIS

• Decision-Making at 1-2 Hours
• CSF Analysis
• CSF smears/stains
• CSF antigen screens
• CSF profile

13
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

14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
17
CEREBROSPINAL FLUID PROFILES

• Neutrophilic/Low glucose (purulent)
• Lymphocytic/Normal glucose
• Lymphocytic/Low glucose
• Profile designation based on WBC differential
• and glucose concentration. After NE Hyslop, Jr
• and MN Swartz, Postgrad Med 58120, 1975.

18
BACTERIAL VS VIRAL MENINGITIS

• Predictors of bacterial etiology
• CSF glucose lt 34
• CSF Serum glucose ratio lt 0.23
• CSF protein gt 220
• CSF WBC count gt 2000
• CSF neutrophil count gt 1180
• Presence of any one of the above finding
• predicts bacterial etiology with gt 99 certainty

19
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

20
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

21
THE PATIENT WITH SUSPECTEDCNS INFECTIONContraind
ications to LP

• Absolute Skin infection over site
• Papilledema
• Relative Increased ICP without papilledema
• Suspicion of mass lesion
• Spinal cord tumor
• Spinal epidural abscess
• Bleeding diathesis

22
CNS INFECTIONSCCT

• Over-employed diagnostic modality ? Leads to
  unnecessary delays in therapy
• Rarely indicated in pt with suspected acute
  meningitis
• Mandatory in pt with possible focal infection
• Increased sensitivity with contrast enhancement

23
CCT Before LP in Patients with Suspected
Meningitis

• 301 pts with suspected meningitis 235 (78) had
  CCT prior to LP
• CCT abnl in 56/235 (24) 11 pts (5) had
  evidence of mass effect
• Features associated with abnl CCT were age gt60,
  immunocompromise, H/O CNS dz, H/O seizure w/in
  the previous wk, selected neuro abnls
• Hasbun, NEJM
  20013451727

24
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 CT had none of
  features present at baseline
• CT normal in 93 of these 96 pts (NPV 97)
• Hasbun, NEJM
  20013451727

25
(No Transcript)
26
THE PATIENT WITH SUSPECTED CNS INFECTIONRole of
Repetitive LPs

• 1. Rarely indicated in proven bacterial
  meningitis unless clinical response not
  optimal or as expected or infection due to
  antibiotic resistant pathogen
• 2. Essential in pts with aseptic meningitis
  syndromes to monitor course/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

27
BACTERIAL MENINGITIS

• Incidence of 3 cases/100,000 population/yr
  (25,000 total cases)
• Fever, HA, meningismus, altered mentation
  present in gt 85 of pts
• Other clinical findings
• Cranial nerve palsies/focal signs 10-20
• Seizures 25-30
• Papilledema lt 1

28
BACTERIAL MENINGITISCaveats re Antimicrobial Rx

• Therapy is genly IV, high dose, bolus
• Dosing intervals should be appropriate for drug
  being administered
• Utilize cidal therapy whenever possible
• Strive for CSF bactericidal index gt 10
• Initiate therapy promptly (ie, within 30 mins)

29
THE THERAPY OF MENINGITISDesirable Antimicrobic
Properties

• 1. Activity vs suspected pathogen(s)
• preferably cidal
• 2. Adequate CSF diffusion
• 3. Acceptable risk of toxicity

30
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
• 8-50 yr
• gt50 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

31
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 ?-
• 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

32
EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

• Clinical Setting Likely Pathogens Therapy
• Community-acquired S. pneumoniae Ceftriaxone
• N. meningitidis 2 gms q12h
• Listeria
• H. influenzae Vancomycin 1-2 gms 12h
• /-
• Ampicillin 2 gm q4h
• Closed head trauma S. pneumoniae Pen G 3-4
  mµ q4h
• Streptococci
  Vancomycin 1-2 gm q12h

33
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
• Open head injury Listeria
  Ceftriaxone 2 gm q12h
• Nosocomial Cefotaxime 2 gm q4h
• Elderly /-
• Ampicillin 2 gm q4h

34
SPECIFIC THERAPY FOR KNOWN PATHOGENS

• Pathogen Recommended Therapy
• S. pneumoniae Pen G 18-24 mµ/d
• N. meningitidis or
• Streptococci Ampicillin 12 gm/d
• Chloro 75-100 mg/kg/d
• Ceftriaxone 2-4 gm/d
• H. influenzae Cefotaxime 12 gm/d
• Ceftriaxone 2-4 gm/d
• Group B strep Pen G 18-24 mµ/d
• or
• Ampicillin 12 gm/d
• plus aminoglycoside

35
SPECIFIC THERAPY FOR KNOWN PATHOGENScontinued

• S. aureus Nafcillin 12 gm/d
• Vancomycin 2 gm/d
• Listeria Ampicillin 12 gm/d
• or
• Pen G 18-24 mµ/d
• plus aminoglycoside
• Gram negative Cefotaxime 12 gm/d
• bacilli Ceftriaxone 2-4 gm/d
• Pseudomonas Ceftazidime 6-8 gm/d
• plus aminoglycoside
• Penicillin-susceptible (i.e. PCN MIC lt 0.06).
  If resistant to penicillin,
• refer to Table 7.

36
SUGGESTED TREATMENT REGIMENS FOR
ANTIBIOTIC-RESISTANT BACTERIAL MENINGITIS

• Suggested Regimen
• Bacteria Antibiotic Dosage
• N. meningitidis Ceftriaxone 2g q12h
• Penicillin MIC 0.1-1.0 µg/ml or
• Cefotaxime 2g q4-6h
• H. influenzae Cefotaxime 2 g every 12h
• ?-Lactamase producing or
• Ceftriaxone 2 g every 4-6h
• S. pneumoniae Vancomycin 1-2 g every 12h
• Highly resistant to
• penicillin (MIC gt 1 ?g/ml) Ceftriaxone 2
  gm every 12h
• /-
• Rifampin 600 mg every 12-24h
• Relatively resistant to Ceftriaxone 2-3 g
  every 12h
• penicillin (MIC 0.1-1.0 ?g/ml) or
  or

37
CORTICOSTEROIDS AND MENINGITIS

• Role of steroids controversial
• Studies in children (1ly with H. flu meningitis)
  have suggested reduced incidence of deafness but
  impact on other neurologic sequelae less clear
• No prospective controlled trials in adults
• Thus, no firm recommendation for routine use of
  steroids in adults can be made.

38
(No Transcript)
39
(No Transcript)
40
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

41
NONVIRAL CAUSES OF ENCEPHALOMYELITIS

• Rocky Mountain spotted fever Acanthamoeba
• Typhus Toxoplasma
• Mycoplasma Plasmodium falciparum
• Brucellosis Trypanosomiasis
• Subacute bacterial endocarditis Whipples
  disease
• Syphilis (meningovascular) Behcets disease
• Relapsing fever Vasculitis
• Lyme disease
• Leptospirosis
• Tuberculosis
• Cryptococcus
• Histoplasma
• Naegleria

42
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 (CCT 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

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