Transcript Encephalitis CBP - UBC Critical Care Medicine

Encephalitis and Meningitis CBP
Yoan Lamarche, 2009
46 yo male presenting to ED with progressive
decreased LOC since 2 days. Able to mumble
answers to questions. No history of recent
travel or drug use. No allergies. On exam,
patient protects A/W, Bp 110/52, HR 92, RR
29, Sat 92% RA T 38.4C. Neck N.
Chest/Abdo N. Skin show no rash. WBC 14
000. CXR N. No focal signs on exam. ABG
shows mild respiratory alkalosis.
Approach to the unconscious Pt
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Naisan
Scot
Noemie
Marios
Neil
Todd
Initial workup, ↓LOC
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Glycemia
ABCs
Physical exam: seizure-localizing-toxidrome
Labs: kidney, liver, sepsis, ABG, AG
CT Head
LP
EEG
Overlapping Tx
2. Describe the usual clinical presentation for
meningitis, including the relative frequency
of different signs and symptoms
Clinical Presentation
• Classical triad
– Fever: 95% on presentation
– Nuchal Rigidity: 88% on initial exam
• Brudzinski sign
• Kernig sign
– Mental status change: 77%
• Triad present in 44% pts on presentation
• Sensitivity of 99% if pt has at least one
finding of the triad
N Engl J Med 1993 Jan 7;328(1):21-8
• How does the bug get to the brain?
Organism
Site of entry
Predisposing conditions
Neisseria meningitidis
Nasopharynx
Usually none, rarely
complement deficiency
Strep. Pneumoniae
Nasopharynx or direct
extension across skull
fracture
All conditions that
predispose to
pneumococcal
bacteremia, fracture of
cribriform plate
Listeria monocytogenes
GI tract, placenta
Defects in cell mediated
immunity
Coagulase-negative
staphylococcus
Dermal or foreign body
Surgery and foreign body,
especially ventricular
shunt
Gram negative rods
Various
Advanced medical illness,
neurosurgery
Haemophilus influenzae
Nasopharynx
Diminished humoral
immunity
taphylococcus aureus
Bacteremia, dermal, or
foreign body
Endocarditis, surgery and
foreign body, especially
ventricular shunt
Major mechanism
• Colonization of the nasopharynx with
subsequent bloodstream invasion and
subsequent central nervous system (CNS)
invasion.
• Invasion of the CNS following bacteremia due
to a localized source, such as infective
endocarditis or a urinary tract infection
Major mechanism
• Direct entry of organisms into the CNS from a
contiguous infection (eg, sinuses, mastoid),
trauma, neurosurgery, a cerebrospinal fluid
(CSF) leak, or medical devices (eg, shunts or
intracerebral pressure monitors or cochlear
implants in children)
2. A)How does the bug get to the brain
Emerg Clin N Am 2009
Clinical Presentation- Meningitis
• 30% Seizure
• 30% Focal Neuro signs
1. ↓ LOC
95% will have > 2 of
2. Fever
3. Neck Stiffness
4. Headache
van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and
prognostic factors in adults with bacterial meningitis. N Engl J Med
2004;351(18):1849–59
Predictors: Bacterial
1.
2.
3.
4.
Seizure
↓LOC
Focal
Shock
1 of those +
•Neutro > 1000/mm3
Most likely Bacterial
Brivet FG, Ducuing S, Jacobs F, et al. Accuracy of clinical presentation for
differentiatingbacterial fromviralmeningitis in adults: amultivariate approach.
IntensiveCareMed 2005;31(12):1654–60
• SiADH more frequent with Bacterial
Meningitis
• BC + in 50% Bacterial
30% other
suppurative focus of
Ix
H influenza b
Asplenia
HIV
Neisseria
Meningitidis
Young adults-children
Deficiency in C5C6-C7-C8±C9
Pneumococcu
s
Adults
Asplenia
Myeloma
Hypogammaglob
R-OH
Basilar skull Fx
50% infections
Listeria
Neonates
ROH
Elderly
Cancer
Immunosupp
Cole slaw
Milk
Cheese
Processed meat
GNB
Head trauma
Neurosurgery
Neonates
S epi
CSF shunts
S aureus
Post neurosurgery
Db, R-OH, CRF, Cancer
Group B Strep
Db, R-OH, Parturient, cardiac disease, collagen, hepatic, renal, steroids
30% other
suppurative
focus of Ix
E coli, Kleb,
Pseudo
Question 3: Describe the initial sequence
of investigations and treatment plan in
a patient with suspicion for meningitis
Initial investigations in suspected bacterial
meningitis
Ensure adequate airway, breathing and circulation.
Stat blood cultures + lumbar puncture
Routine septic blood work (CBC, lytes, Creat, LFTs,
lactate, coags)
ABG
Chest X-ray
Contraindications to LP
• Theoretical risk of brain herniation following
lumbar puncture in pts with increased ICP.
IDSA criteria for pre-LP CT head:
Tunkel A, et al. Practice Guidelines for the Management of Bacterial Meningitis (IDSA Guidelines). CID 2004;39:1267-84
Other relative contraindications to LP
• Thrombocytopenia (plts < 50 000)
• Coagulopathy or systemic anticoagulation
(INR > 1.4).
• Epidural abscess or infection over LP site
Initial management in suspected bacterial
meningitis
Tunkel A, et al. Practice Guidelines for the Management of Bacterial Meningitis (IDSA Guidelines). CID 2004;39:1267-84
Lancet ID 2007
LP: Complications: IDSA Guidelines
2004
An LP is done after a CT of the head showing
8000 WBC/μl
4. Describe the findings on LP, what if traumatic?
LP: send for
• Cell count, differential
• Biochemistry (gluc-proteins)
• Stains and cultures for bacteria, fungi and
mycobacteria
• Viral studies-HSV PCR (Sen 98%, Spe
94%,NPV suboptimal)
Latex Agglutination
• Sen 50-100%
• Spe <100
• Does not change tx in Bacterial Meningitis
(treat or not with ATBX)
• May be useful if received ATBX and CSF
clear
Broad Range Real time PCR
• Sensitivity of 86%-100%
• Specificity of 98% when compared with culture
-Deutch S, Pedersen LN, Podenphant L, et al. Broad-range real time PCR and
DNA sequencing for the diagnosis of bacterial meningitis. Scand J Infect Dis
2006;38(1):27–35.
-Saravolatz LD,Manzor O, VanderVelde N, et al. Broad-range bacterial
polymerase chain reaction for early detection of bacterial meningitis. Clin
Infect Dis 2003;36(1):40–5.
Acute Phase reactants
•Nathan BR, Scheld WM. The potential roles of C-reactive protein and procalcitonin concentrations in the serumand cerebrospinal fluid in the
diagnosis of bacterialmeningitis. Curr Clin Top Infect Dis 2002;22:155–65.
•Gendrel D, Raymond J, Assicot M, et al. Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis
1997;24(6):1240–2.
•Viallon A, Zeni F, Lambert C, et al. High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect
Dis 1999;28(6):1313–6.
•ViallonA,Guyomarc’h P,Guyomarc’h S, et al.Decrease in serumprocalcitonin levels over time during treatment of acute bacterial meningitis.
Crit Care 2005;9(4):R344–50
Post Neurosurgery
• Lactate > 4mmol/l: higher risk of
meningitis
• Sensitivity was 88%
• Specificity was 98%.
• The positive predictive value was
96%
• Negative predictive value was 94%
• RT-PCR may have high SEN,
research
Leib SL, Boscacci R, Gratzl O, et al.
Predictive value of cerebrospinal fluid (CSF)
lactate level versus CSF/blood glucose ratio
for the diagnosis of bacterial meningitis
following neurosurgery. Clin Infect Dis
1999;29(1):69–74.
.
Pfausler et al
Lancet 2007
Neurol Clin 2008
Viral encephalitis Review Solomon
2007
• 5. What is the bacteriology of bacterial
meningitis? (Scot)
• Historical
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H influenzae (45%)
S pneumoniae (18%)
Neisseria meningitidis (14%)
Group B streptococcus (S agalactiae) (6%)
Listeria monocytogenes (3%)
Others (14%)
Children < 5 years old >70% H influenzae
• HIB vaccine introduced in 1990s.
• Since HIB vaccination
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S pneumoniae (47%)
N meningitidis (25%)
group B streptococcus (12%)
Listeria monocytogenes (8%)
H influenzae (7%)
Others (1%)
• Remains to be seen whether proportions will
change with the increasingly widespread use
of S pneumoniae multivalent vaccines.
• In infants where it has been used, invasive S
pneumoniae disease has decreased by
>90%.
6-What should you initiate as a treatment for
your now intubated unconscious febrile
patient with possible meningitis? Is there
resistance to this treatment?
Empiric Treatment for Bacterial
Meningitis
• ABCs, as above.
• Critical care setting, given decreased LOC
and sepsis requiring airway protection and
ventilatory support.
• Fluid resuscitation as required.
• Immediate antibiotics.
Empiric Treatment for Meningitis
• 3rd-generation cephalosporin, i.e. ceftriaxone
2 g IV q 12 hrs (maximize CSF concentration
with this dose).
• Vancomycin 1.5 g IV X1, then 1 g IV q 12 hrs.
– For pneicillin-resistent pneumococci
• +/- ampicillin if risk factor for Listeria
monocytogenes
– Alcoholism, immunosuppression
Resistance to Initial Antibiotics
• Antimicrobial resistant organisms:
– Strep pneumo: may be resistant to penicillin
(hence empiric vancomycin); approx 10% across
VCH.
– Neisseria meningitidis: often resistant to penicillin
(hence empiric 3rd-generation cephalosporin)
– May add rifampin if resistant to ceftriaxone (MIC >
2mg/L)
• Wrong organism
– Viral
– Fungal
Van de Beek, NEJM 2006
Directed Pharmacotherapy of CNS Infections:
What Intensivists SHOULD Know
 What are the in vitro susceptibility results (if culture
positive)?
 Is the antibacterial bactericidal in the CNS?
 Subarachnoid space/brain tissue are regions of ineffective
host defence
 Antibiotics must demonstrate bactericidal activity in vivo
 What is the antibacterial concentration attainable
in CNS?
Central Nervous System Compartments

The Brain and CSF cannot be viewed as 1
pharmacokinetic (PK) compartment!

Three distinct PK compartments within the CNS
1. CSF
2. Extracellular space of neuron tissue
3. Intracellular space (neurons, glial cells, granulocytes,
lymphocytes, macrophages)

Drugs penetrate into each of these compartments
to varying degrees

CSF is not homogeneous (drug concentration
higher in lumbar versus ventricular CSF)
Blood-Central Nervous System Interfaces
 Blood-Brain Barrier
 Located in endothelial cells of vessels of brain and spinal cord
 Linked by tight junctions
 Only 0.02% of brain capillaries possess fenestrated
endothelium
 Blood-CSF Barrier
 Choroid plexus is characterized by fenestrated vascular
endothelium
Blood-Central Nervous System Interfaces
Blood-CSF Barrier
Blood-Brain Barrier
Most Important Drug-Factors Associated with
Antibacterial CNS Concentration
 Molecular Size (smaller molecules pass better)
 Lipophilicity (lipophilic molecules pass better)
 Drug-Plasma Protein Binding (low protein binding
enhances CNS penetration)
Less Important Drug-Factors Associated with
Antibacterial CNS Concentration
 Active transport into CSF (low clinical significance)
 Low capacity, facilitated diffusion system at blood-brain
barrier exists for some penicillins/cephalosporins
 Active efflux from CSF (pump located in 3rd/4th
ventricles)
 Molecular charge (low clinical significance)
 Weak acids, such as penicillins/cephalosporins will be nonionised in acidic CSF (more readily pass from CSF back
into blood compartment)
 Metabolism at the barriers
 This is why IV dopamine is not useful for PD
Meningeal Inflammation and  CNS
Drug Concentrations: Why?
• Alteration of barrier permeability
– Antibiotic therapy  inflammation and CNS penetration 's
over course of treatment
– Corticosteroid therapy  inflammation and 's CNS
penetration
• Inhibitory effect on CSF drug-efflux pump
•  CSF production   CSF bulk flow   CSF drug
clearance   CNS drug concentration
Neuro Clin 2008
Empiric antibiotics
van de Beek D, et al. Community- acquired bacterial meningitis in adults. N Engl J Med 2006; 354: 44–53.
Antibiotic doses
Fitch MT, van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis 2007; 7:191-200
Empiric regimens
• Dexamethasone 10 mg IV q6h x 4 days (dose to
be given with or before first antibiotic dose)
• Ceftriaxone 2 g IV q12h (or Cefotaxime 2 g IV
q6h)
• Vancomycin 15 mg/kg IV q12h
• Amoxicillin 2 g IV q4h
Tx Meningitis
Add Dexamethasone 10mg IV q 6 x 4d pre ATBx for all. STOP if not Pneumococcus
Tx Meningitis
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Bacterial: 10-14d
Meningococcus: 7d
E coli and GNB: 21d
S agalactiae: 14-21d
L monocytogenes: 21d
If Not Pneumococcus: D/C steroids (IDSA), If
Resistant pneumococcus: Stop Steroids
(decrease Vanco penetration in CNS)
• If already on ATBX, do not initiate Steroids
NEJM 2006, van de Beek review
IDSA Guidelines 2004
• IDSA GUIDELINES 2004
IDSA 2004
7- Should this patient receive steroids? What is
the evidence for steroids in bacterial
meningitis? Neil
Should this patient receive steroids?
What is the evidence for steroids in
bacterial meningitis?
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18 studies 2750 pts
Mortality RR 0.83 (0.71-0.99)
Hearing loss RR 0.65 (0.41-0.91)
Neuro sequelae RR 0.67 (0.45-1.00)
After 3 days, the patient’s partner appears in
the unit, claiming they both have HIV, are on
triple therapy, but that they are not together
for the past 3 months.
8-What is the differential diagnosis of
decreased LOC in the HIV patient with a CNS
infection? At what levels of CD4 will you find
those infections? Describe the typical
investigations and typical findings for each of
those infections
DDX of CNS infections in HIV
CD4
count
CSF
TESTS
TB
Any, but
usually
<250
Inc. protein and WBC
Dec glucose
BUT can be N
AFB
Culture
Toxoplasma
Encephalitis
< 200
Usually contraindicated
CT Scan
IgG/IgM
Cryptococcal
Meningitis
< 100
++opening pressure
Inc protein and monos.
N glucose
Antigen
(94.1% spec)
Culture
CMV Encephalitis
< 50
Inc protein and monos
PCR
Antigen
cytology
Progressive Multifocal
leukoencephalopathy
< 250
Normal
PCR of CST
CT scan
Primary CNS
lymphoma
< 100
Inc protein
PCR of EBV
CT Scan
DDX of CNS infections in HIV
• Not CD4 dependant
– Abscess
• Staph/strep/aspergillus/nocardia/listeria
– Syphillis
– Neurocysterocosis
– All the regular other stuff (bacterial, viral)
Three days after the initiation of antibiotics, the
patient wakes up with progressive signs of R
sided paralysis
9- What are the complications of bacterial
meningitis? Noemie
– When to initiate ICP monitoring
– When to do EEG
Neurological complications
• Altered mental status
– 3 % have severe disability at 8 wks
• Increased ICP
– headache, confusion, irritability, N/V
• Seizures
– Occur in 5% before admission and 15% after
admission
– More common with pneumococcal meningitis
– associated with a higher risk of neurologic deficits
at hospital discharge (24 versus 6 percent)
Uptodate.com
Major CNS complications
N Engl J Med 2006;354:44-53
Mortality
• Mortality from Strep Pneumonia:19-37%
• Mortality from Meningococcus: 3-13%
• Strongest RFs for an unfavorable outcome
are:
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evidence of systemic compromise
impaired consciousness
low WBC in the CSF
Infection with S. pneumonia
Complications
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Shock (15%)
Seizures (30%)
SiADH
Subdural empyema
Epidural abcess
Increased ICP
EmClinNAm 2009
While you are treating your patient
for this complication, the partner
collapses, seizing. You intubated him
and send him to emergency. After he
stopped seizing, he remains
unresponsive.
Question 10: Describe the clinical
presentation of typical viral encephalitis
Classical presentation of viral encephalitis
• An acute flu-like prodrome developing into an
illness with high fever, severe headache,
nausea, vomiting and altered consciousness
• Often associated with seizures and focal
neurological signs lethargy, drowsiness,
confusion, disorientation.
Solomon T, et al. Viral Encephalitis: a clinician’s guide. Pract Neurol 2007; 7: 285–302
MENINGITIS VERSUS
ENCEPHALITIS
•
The presence or absence of normal brain function is the important distinguishing
feature between encephalitis and meningitis.
•
In encephalitis, abnormalities in brain function are expected including:
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Altered mental status
Motor or sensory deficits
Altered behavior and personality changes
Speech or movement disorders.
Hemiparesis
Flaccid paralysis
Paresthesias
•
Patients with meningitis may be uncomfortable, lethargic, or distracted by headache,
but their cerebral function remains normal.
•
Seizures and postictal states can be seen with meningitis alone and should not be
construed as definitive evidence of encephalitis.
Johnson RP, Gluckman SJ. Viral encephalitis in adults. www.UpToDate.com
Clinical presentation
Type
Clinical Picture
1-2weeks post
immuniz- post viral
Postinfectious
Fulminant
Eastern Equine
Herpes Simplex
Slowly progressive
Creutzfeld Jacob/Variant
Subacute sclerozing
panencephalitis (SSPE)
AIDS
Chronic-fluctuating
mycobacteria
Fungal (Mucor may be
rapid)
Cause
Clues
Arbovirus
Season, locale, degree of
insect exposure
Rocky Mountain
spotted fever
Tick
Eastern Equine
Local horses or pheasants,
enzootic area
West Nile
Outbreaks in dead birds
St-Louis
Serologis changes in
chickens
Lyme
Tick
Rabies
Racoons, Bats, Fox, dogs
Ehrlichiosis
Tick
Leptospirosis
Animals
Herpes Simplex
HSV
Tests
The patient partner is now 39.5C and shivers, a
rash appears all over his body. He is still
unconscious. He is not receiving antibiotics.
You wonder if this could be a Meningococcal
meningitis
11. Describe the post exposure prophylaxis in
bacterial meningitis for the resident who
intubated him. For you, as a supervisor. For
the nurses. For his family. (Scot)
Post-exposure prophylaxis
• Incidence of transmission of Meningococcus
among household contacts is about 5%
(increased risk of developing meningitis by
500-800 times).
• 1/3 of secondary cases develop in 2-5 days,
so prompt appropriate prophylaxis necessary
for high risk contacts.
High-risk, non-healthcare:
• Household (slept or ate in same household).
• Intimate nonhousehold with mucosal contacts
(sexual partner).
• Direct exposure to secretions (shared
utensils, toothbrushes, kissing,
school/daycare) in previous seven days.
High risk, healthcare:
• direct mucosal contact with the patient’s
secretions (mouth-to-mouth resuscitation,
endotracheal intubation, or suctioning of the
airway.)
Prophylactic regimens:
• rifampin 600 mg dose for adults, 10 mg/kg
every dose for children older than 1 month, 5
mg/kg every dose for neonates (age less than
or equal to 30 days) orally every 12 hours for
a total of four doses.
• alternative single dose regimens:
ciprofloxacin 500 mg by mouth for adults or
ceftriaxone 250 mg IM (age greater than or
equal to 12 years) or 125 mg IM (age less
than 12 years).
Prophylaxis for other organisms:
• H influenzae: Rifampin for nonpregnant
household contacts if there are young
children (age younger than 4 years) in the
household.
• Chemoprophylaxis is not given for
pneumococcal meningitis.
12- Describe the long term outcomes of patients
with bacterial meningitis Todd
Long-Term Outcomes in Bacterial
Meningitis
• Death.
– Mortality is approximately 25% in adults (NEJM
1993, of 493 episodes), up to 50% in geriatric
population.
– Driven by S. pneumoniae; around 5% for H
influenzae or N meningitidis, or GBS.
– Poor prognostic factors include:
• Decreased LOC at admission, increased ICP, seizures
within 24 hours of admission, need for mechanical
ventilation, delayed treatment, age > 50 yrs, medical
comorbidities.
• Presence of osteitis or sunusitis, thrombocytopenia,
tachycardia, low CSF cell count, elevated ESR, positive
blood cuture and absence of rash.
Long-Term Outcomes in Bacterial
Meningitis. Up to 60% have one or
more of:
• Hearing loss (mainly in
children)
• Cognitive impairment
• Personality changes
• Gait disturbances,
dizziness
• Blindness
• Seizures
• Paralysis/paresis
•
•
•
•
•
•
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Hydrocephalus
Subdural abscess
Subdural effusion
Subdural empyema
Epidural abscess
Cerebral thrombosis
Cerebral vasculitis
De Beek, NEJM 2004
13- As you were ordering some cipro for the
sister who just showed up in the unit, she tells
you about an envelope containing white
powder that her brother received a couple
days ago. What is the clinical presentation of
Anthrax? Treatment? Outcome? Todd
Just say “NO” to white powder…
•
•
•
•
Anthrax:
Not just a thrash band from the 80s.
One more reason to fear post offices.
3 clinical presentations:
– Cutaneous
– Inhalation
– Gastrointestinal
Cutaneous Anthrax
• Usually through contact with infected animals
or animal products.
• Small, occasionall pruritic papules that
quickly enlarge to develop central vesicles or
bullae, followed by erosion to necrotic ulcer.
• Regional lymphadenopathy and edema of
surrounding tissue.
• May develop systemic symptoms, including
fever, malaise and microangiopathic
hemolytic anemia/ coagulopathy and renal
failure.
Inhalation Anthrax
• Incubation period usually 1 to 7 days
(reported to be as long as 43 days).
• Nonspecific symptoms at first, such as fever,
malaise, mylagia.
• Progresses to hypoxia and respiratory failure,
with hypotension, cyanosis and stridor.
• May progress to hematogenous spread,
including hemorrhagic meningitis.
• Untreated, it’s fatal. 45 % mortality with
treatment in 2001 bioterror event in US.
Gastrointestinal Anthrax
• Oropharyngeal
– Oropharyngeal edema, with necrotic
pseudomembranous ulcers, pharyngitis and
cervical lymphadenopathy.
• Diarrheal
– Intestinal and mesenteric edema, with associated
lymphadenopathy. Necrotic ulcers may form.
– Presents with N/V, abdominal pain, anorexia and
possibly hematemesis or bloody diarrhea. May
proceed to toxemia, shock and death.
• Overall case fatality rate 25-60%.
Diagnosis
• History (cloud of white powder in the post
office, or at work after a creepy guy got fired)
• Clinical (as above)
• Stool, sputum, pleural fluid and blood at 2-8
degrees C
• Room temp swabs
• Formalin-fixed tissue samples.
• Frozen tissue samples
– All for C&S and PCR (B. anthracis), with several
immunochemical tests available (i.e. ELISA*,
immunohistochemistry, Redline Altert S-layer protein*)
– Most go to CDC/Lab response network.
– * = commercially available
Treatment
• Bacillus anthracis is highly susceptible to many antibiotics,
including:
– Fluoroquinolones
– Erythromycin
– Tetracycline, Doxycycline
– Chloraphenicol
– Streptomycin
– Vancomycin
– Rifampin
• NOT to cephalosporins or TMP/SMX
• Treat for 60 days in event of bioterrorism-related exposure, due
to risk of inhalational anthrax.
Empiric Regimen
• Adults and children;
– Ciprofloxacin or Doxycycline IV plus clindamycin,
vancomycin, rifampin or a carbapenem
• Pregnant women
– Same, with cipro preferred over doxy.
Toxoplasma Gondii Encephalitis in HIV
+
Toxo encephalitis
•
•
•
•
IDSA Guidelines HIV 2008
Rare if CD4+>200, more if < 50cells/ul
Fever, confusion, motor weakness, headache
Dx
– CT: mass lesions
– Syndrome
– Tissue/Microbio Dx (if fails to respond to Tx, need
Bx)
Toxo encephalitis
DDx:
Lymphoma
MycoB (Tb)
Fungi (Crypto)
PML (Progressive multifocal leukoencephalopathy)
Chagas
PML
Toxo
White matter
Gray matter
no mass effect
enhancement
no enhancement
mass effect
Toxo encephalitis, Tx
1. Pyrimethamine + sulfadiazine
2. Pyrimethamine + clinda + leucovorin
3. TMP+SMX (If IV, TMP-SMX IV vs PO Pyrimethamine + IV Clinda)
Side effects Toxo drugs
•
•
•
•
•
Pyrimethamine
– rash, nausea,
– Bone marrow suppression (neutropenia, anemia, and
thrombocytopenia) that can often be reversed by increasing the
dose of leucovorin to 50–100 mg/day administered in divided doses
(CIII).
Sulfadiazine
– rash, fever, leukopenia, hepatitis, nausea, vomiting, diarrhea, and
crystalluria.
Clindamycin
– fever, rash, nausea, diarrhea (including pseudomembranous colitis
or diarrhea related to Clostridium difficile toxin), and hepatotoxicity.
TMP-SMX
– rash, fever, leukopenia, thrombocytopenia, and hepatotoxicity.
Drug interactions between anticonvulsants and antiretroviral agents
Management of Treatment Failure
Toxo
A brain biopsy, if not previously performed, should be strongly considered for
patients who fail to respond to initial therapy for TE (BII) as defined by clinical
or radiologic deterioration during the first week despite adequate therapy or
lack of clinical improvement within 2 weeks. For those who undergo brain
biopsy and have confirmed histopathologic evidence of TE, a switch to an
alternative regimen as previously described should be considered (BIII)