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Chapter 2. Empiric Therapy: CNS Infections Encephalitis
Usual Pathogens
IV-to-PO Switch
Acyclovir 10 mg/kg (IV) q8h x 7 days, then if able to take oralmedications, complete 14-21 days of total therapy withacyclovir 400 mg (PO) 5x/day or valacyclovir 1 gm (PO) q8h or famciclovir 500 mg (PO) q8h Usual PathogensCalifornia encephalitis (CE), Western equine encephalitis (WEE), Venezuelan equineencephalitis (VEE), Eastern equine encephalitis (EEE), St. Louis encephalitis (SLE),Japanese encephalitis (JE), West Nile encephalitis (WNE) Preferred IV TherapyDoxycycline 200 mg (IV) q12h x 3 days, then 100 mg (IV) q12hx 2-4 weeksAlternate IV TherapyMinocycline 100 mg (IV) q12h x 2-4 weeksIV-to-PO SwitchDoxycycline 200 mg (PO) q12h x 3 days, then 100 mg (PO)q12h x 2-4 weeks* q24h + folinic acid 10 mg (PO) q24h + folinic acid 10 mg (PO)q24h Ganciclovir 5 mg/kg (IV) q12h Foscarnet 60 mg/kg (IV) q8hx 3 weeks, followed by Duration of therapy represents total time IV or IV + PO. Most patients on IV therapy able to take PO meds shouldbe switched to PO therapy after clinical improvement* Loading dose is not needed PO if given IV with the same drug* Consider discontinuation of therapy if CD > 200 for ≥ 6 months in response to antiretroviral therapy † Consider discontinuation of therapy if CD > 100-150 for ≥ 6 months in response to antiretroviral therapy Chapter 2. Empiric Therapy: CNS Infections Herpes Encephalitis (HSV-1)
Clinical Presentation: Acute onset of fever and change in mental status without nuchal rigidity
Diagnostic Considerations: EEG is best early (< 72 hours) presumptive test, showing unilateral
temporal lobe abnormalities. Brain MRI is abnormal before CT scan, which may require several days
before a temporal lobe focus is seen. Definitive diagnosis is by CSF PCR for HSV-1 DNA. Usually presents
as encephalitis or meningoencephalitis; presentation as meningitis alone is uncommon. Profound
decrease in sensorium is characteristic of HSV meningoencephalitis. CSF may have PMN predominance
and low glucose levels, unlike other viral causes of meningitis
Pitfalls: Rule out non-infectious causes of encephalopathy
Therapeutic Considerations: HSV is the only treatable common cause of viral encephalitis in normal
hosts. Treat as soon as possible, since neurological deficits may be mild and reversible early on, but
severe and irreverisible later
Prognosis: Related to extent of brain injury and early antiviral therapy
Arboviral Encephalitis
Clinical Presentation: Acute onset of fever, headache, change in mental status days to weeks after
inoculation of virus through the bite of an infected insect (e.g., mosquito/tick). May progress over
several days to stupor/coma
Diagnostic Considerations: Diagnosis by specific arboviral serology
Pitfalls: Usually occurs in summer/fall. Diagnosis suggested by arboviral contact/travel history.
Electrolyte abnormalities due to syndrome of inappropriate antidiuretic hormone (SiADH) may occur
Therapeutic Considerations: Only supportive therapy is available at present
Prognosis: Permanent neurological deficits are common, but not predictable. May be fatal
Mycoplasma Encephalitis
Clinical Presentation: Acute onset of fever and change in mental status without nuchal rigidity
Diagnostic Considerations: Diagnosis suggested by CNS and extra-pulmonary manifestations—sore
throat, otitis, E. multiforme, soft stools/diarrhea—in a patient with community-acquired pneumonia,
elevated IgM Mycoplasma titers, and very high (≥ 1:1024) cold agglutinin titers. CSF shows mild
mononucleosis/pleocytosis and normal/low glucose
Pitfall: CNS findings may overshadow pulmonary findings
Therapeutic Considerations: Macrolides will treat pulmonary infection, but not CNS infection (due
to poor CNS penetration)
Prognosis: With early treatment, prognosis is good without neurologic sequelae
Toxoplasma Encephalitis (T. gondii)
Clinical Presentation: Wide spectrum of neurologic symptoms, including sensorimotor deficits,
seizures, confusion, ataxia. Fever/headache are common
Diagnostic Considerations: Diagnosis by characteristic radiographic appearance and response to
empiric therapy in a Toxoplasma seropositive patient
Pitfalls: Use folinic acid 10 mg (PO) daily with pyrimethamine-containing regimens, not folate.
Radiographic improvement may lag behind clinical response
Therapeutic Considerations: Alternate agents include atovaquone, azithromycin, clarithromycin,
minocycline (all with pyrimethamine if possible). Decadron 4 mg (PO or IV) q6h is useful for
edema/mass effect
Prognosis: Usually responds to treatment if able to tolerate drugs. Clinical response is evident by 1
week in 70%, by 2 weeks in 90%. Radiographic improvement is usually apparent by 2 weeks.
Neurologic recovery is variable
Chapter 2. Empiric Therapy: CNS Infections CMV Encephalitis
Clinical Presentation: Fever, mental status changes, and headache evolving over 1-2 weeks. True
meningismus is rare. CMV encephalitis occurs in advanced HIV disease (CD < 50/mm3), often in
patients with prior CMV retinitis
Diagnostic Considerations: CSF may show lymphocytic or neutrophilic pleocytosis; glucose is often
decreased. Characteristic findings on brain MRI include confluent periventricular abnormalities with
variable degrees of enhancement. Diagnosis is confirmed by CSF CMV PCR (preferred), CMV culture,
or brain biopsy
Pitfalls: A wide spectrum of radiographic findings are possible, including mass lesions (rare). Obtain
ophthalmologic evaluation to exclude active retinitis
Therapeutic Considerations: Ganciclovir plus foscarnet may be beneficial as initial therapy for severe
cases. Consider discontinuation of valganciclovir maintenance therapy if CD increases to > 100-150/mm3
x 6 months or longer in response to antiretroviral therapy
Prognosis: Unless immune reconstitution occurs, response to therapy is usually transient, followed by
progression of symptoms
Brain Abscess/Subdural Empyema/Cavernous Vein
Thrombosis/Intracranial Suppurative Thrombophlebitis
Preferred IV
Alternate IV
Pathogens
IV-to-PO Switch
Brain Abscess (Single Mass Lesion)
MRSA/MRSELinezolid 600 mg (IV) q12h x 2 weeks x 2 weeks
plus
Metronidazole
1 gm (IV) q24h
x 2 weeks
Chapter 2. Empiric Therapy: CNS Infections Brain Abscess/Subdural Empyema/Cavernous Vein
Thrombosis/Intracranial Suppurative Thrombophlebitis
Preferred IV
Alternate IV
Pathogens
IV-to-PO Switch
x 2 weeks
plus
Metronidazole
1 gm (IV) q24h
x 2 weeks
Brain Abscess (Multiple Mass Lesions)
x 2 weeks
or
Meropenem
1 gm (IV) q8h
x 2 weeks
x 2 weeks
plus
Metronidazole
1 gm (IV) q24h
x 2 weeks
MSSA/MRSA = methicillin-sensitive/resistant S. aureus; MSSE/MRSE = methicillin-sensitive/resistant S. epidermidis.
Duration of therapy represents total time IV or IV + PO. Most patients on IV therapy able to take PO meds shouldbe switched to PO therapy after clinical improvement Clinical Presentation: Variable presentation, with fever, change in mental status, cranial nerve
abnormalities ± headache
Diagnostic Considerations: Diagnosis by CSF gram stain/culture. If brain abscess is suspected, obtain
head CT/MRI. Lumbar puncture may induce herniation
Pitfalls: CSF analysis is negative for bacterial meningitis unless abscess ruptures into ventricular system
Therapeutic Considerations: Treatment with meningeal doses of antibiotics is required. Large single
abscesses may be surgically drained; multiple small abscesses are best treated medically
Prognosis: Related to underlying source and health of host
Brain Abscess (Mastoid/Otitic Source)
Diagnostic Considerations: Diagnosis by head CT/MRI demonstrating focus of infection in mastoid
Pitfalls: Rule out associated subdural empyema
Therapeutic Considerations: ENT consult for possible surgical debridement of mastoid
Prognosis: Good. May require mastoid debridement for cure
Chapter 2. Empiric Therapy: CNS Infections Brain Abscess (Dental Source)
Diagnostic Considerations: Diagnosis by panorex x-rays/gallium scan of jaw demonstrating focus
in mandible/erosion into sinuses
Pitfalls: Apical root abscess may not be apparent clinically
Therapeutic Considerations: Large single abscess may be surgically drained. Multiple small abscesses
are best treated medically. Treat until lesions on CT/MRI resolve or do not become smaller on therapy
Prognosis: Good if dental focus is removed
Brain Abscess (Subdural Empyema/Sinus Source)
Diagnostic Considerations: Diagnosis by sinus films/CT/MRI to confirm presence of sinusitis/bone
erosion (cranial osteomyelitis/epidural abscess). Usually from paranasal sinusitis
Pitfalls: Do not overlook underlying sinus infection, which may need surgical drainage
Therapeutic Considerations: Obtain ENT consult for possible surgical debridement of sinuses
Prognosis: Good prognosis if sinus is drained
Brain Abscess (Cardiac Source; Acute Bacterial Endocarditis)
Diagnostic Considerations: Diagnosis by blood cultures positive for acute bacterial endocarditis (ABE)
pathogen and multiple brain lesions on head CT/MRI
Pitfalls: Do not overlook right-to-left cardiac shunt (e.g., patent foramen ovale, atrial septal defect)
as source of brain abscess. Cerebral embolization results in aseptic meningitis in SBE, but septic
meningitis/brain abscess in ABE (due to high virulence of pathogens)
Therapeutic Considerations: Multiple lesions suggest hematogenous spread. Use sensitivity of blood
culture isolates to determine coverage. Meningeal doses are the same as endocarditis doses
Prognosis: Related to location/size of CNS lesions and extent of cardiac valvular involvement
Brain Abscess (Pulmonary Source)
Diagnostic Considerations: Diagnosis suggested by underlying bronchiectasis, empyema, cystic
fibrosis, or lung abscess in a patient with a brain abscess
Pitfalls: Brain abscesses are associated with chronic suppurative lung disease (e.g., bronchiectasis, lung
abscess/empyema), not chronic bronchitis
Therapeutic Considerations: Lung abscess may need surgical drainage
Prognosis: Related to extent/location of CNS lesions, drainage of lung abscess/empyema, and control
of lung infection

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