Viral encephalitis medical therapy

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Template:Encephalitis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Priyamvada Singh, MBBS [2]; João André Alves Silva, M.D. [3]

Overview

Encephalitis is an acute inflammation of the brain, commonly caused by a viral infection. Sometimes, encephalitis can result from a bacterial infection, such as bacterial meningitis, or it may be a complication of other infectious diseases like rabies (viral) or syphilis (bacterial). Certain parasitic or protozoal infestations, such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune systems. Treatment with acyclovir with or without steroids and antibiotics should be initiated as soon as possible.[1] Antiviral agent like acyclovir has been useful in treatment of encephalitis due to herpes simplex virus and varicella zoster. Treatment for other causative agents of encephalitis is mostly supportive.

Medical Therapy

General Considerations

  • Reliably tested specific antiviral agents are available only for a few viral agents (e.g. acyclovir or ganciclovir for herpes simplex virus and varicella-zoster encephalitis). Administer the first dose of acyclovir as soon as possible (in the emergency department itself). Acyclovir can be initiated with or without antibiotics or steroids.The advantages of an early antiviral drug administration are:
    • Decreases disease duration
    • Decreases development of latency
    • Decreases development of complications
    • Decreases recurrence
    • Decreases transmission from infected person
  • Treatment for Toxoplasma gondii and cytomegalovirus encephalitis are available but are used with limited success
  • Treatment is usually symptomatic. In patients who are very sick, supportive treatment, such as mechanical ventilation, is equally important.
  • Systemic complications like hypotension, shock, hypoxemia, electrolyte imbalances (hyponatremia, SIADH should be treated promptly.
  • Neuroimaging with MRI or CT scan should be done before lumbar puncture especially if raised intracranial pressure is suspected.
  • Lab tests like blood samples should be taken before initiation of therapy.
  • Bed rest, plenty of fluids and anti-inflammatory drugs to relieve headache and fever should be used.

Empirical Treatment Regimen

  • Adult & Pediatrics - Acyclovir, 10 mg/kg body weight, 8hourly, intravenous, for 2-3 weeks.
  • Neonatal HSV - Acyclovir 10-15 mg/kg 8hourly, intravenous, for neonatal HSV
  • HIV Positive - Foscarnet is generally the treatment of choice given the high incidence of acyclovir resistance in these group of patients.

Treatment for Increased Intracranial Pressure

General

  • Elevation of head end of the bed
  • Hyperventilation may be used to decrease intra-cranial pressure on emergency basis
  • Constant monitoring of neurological status
  • Avoid increase in intra cranial pressure i.e. control of straining and coughing
  • Antipyretics and analgesic for fever and pain.
  • Monitoring and preventing seizures and hypotension.

Drug Therapy

  • Furosemide 20 mg iv and mannitol 1 gm/kg intravenously for diuresis (blood pressure and CVP should be monitored while administrating these drugs)
  • Dexamethasone 10mg intravenously 6 hourly to decrease cerebral edema.

Encephalitis Drug Summary

Acyclovir

  • It is effective for HSV1, HSV2 and varicella zoster.
  • It is selectively taken up by the body cells infected with HSV and varicella zoster
  • Prompt treatment with acyclovir is useful in decreasing complications, latency and communicability
  • Side effects may include nausea, vomiting, diarrhea, loss of appetite, and muscle or joint pain. Rarely, serious adverse effects may include renal and liver functions abnormalities or suppression of bone marrow activity.

Foscarnet

  • It is effective against HSV 1, HSV 2 and CMV
  • It is useful in patients who have developed resistance or are non-responders against acyclovir for e.g. HIV positive patients
  • Drug dosage depends on the renal function of the patient as Foscarnet is excreted through kidneys.

Dexamethasone

  • It is used in post-infectious and disseminated encephalitis.
  • It may be used as an adjunct with the antiviral agents

Furosemide

  • It is used to in encephalitis associated with increased intracranial pressure. The mechanism of action is;
    • It decreases the production of CSF by inhibiting carbonic anhydrase enzymes.
    • Decreases cerebral sodium uptake
    • Inhibits cellular membrane chloride pumps.
  • The dose should be individualized for patients

Mannitol

  • Used only on short term basis.
  • The doses should be individualized based on renal function

Lorazepam

  • It is used for treatment of seizures associated with encephalitis.

Empiric Therapy [2] [3]

▸ Click on the following categories to expand treatment regimens.

Empiric Therapy

  ▸  Suspected encephalitis

  ▸  Antimicrobials based on epidemiology/clinic

  ▸  Rickettsial/ Ehrlichial infection

  ▸  Acute Disseminated Encephalomyelitis

Suspected encephalitis
Preferred Regimen
Acyclovir Neonates: 20 mg/kg IV q8h for 21 days; Children and Adults with normal renal function: 10 mg/kg IV q8h for 14-21 days
Antimicrobials based on epidemiology/clinic
Preferred Regimen
Please refer to Pathogen-based therapy according to epidemiology and clinical evaluation
Rickettsial/ Ehrlichial infection
Preferred Regimen
Acyclovir Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10 mg/kg IV q8h
PLUS
Doxycycline 200 mg/d in two divided doses
Alternative Regimen
Tetracycline 25-50 mg/kg per day Oral, in four divided doses
Acute Disseminated Encephalomyelitis
Preferred Regimen
Acyclovir Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10 mg/kg IV q8h
PLUS
Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day[4]

Pathogen-Based Therapy — Viruses [5] [3]

▸ Click on the following categories to expand treatment regimens.

Viruses

  ▸  Herpes simplex

  ▸  Varicella-zoster virus

  ▸  Cytomegalovirus

  ▸  Epstein-Barr virus

  ▸  Human herpesvirus 6

  ▸  B virus

  ▸  Influenza virus

  ▸  Measles virus

  ▸  Nipah virus

  ▸  West Nile virus

  ▸  Japanese encephalitis virus

  ▸  St. Louis encephalitis virus

  ▸  HIV

  ▸  JC virus

Herpes simplex
Preferred Regimen
Acyclovir Neonates: 20 mg/kg IV q8h for 21 days; Children and Adults with normal renal function: 10 mg/kg IV q8h for 14-21 days
Varicella-zoster virus
Preferred Regimen
Acyclovir Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10-15 mg/kg IV q8h for 10-14 days
PLUS
Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day[6]
Alternative Regimen
Ganciclovir 5 mg/kg IV q12h for 14-21 days
PLUS
Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day[7]
Cytomegalovirus
Preferred Regimen
Ganciclovir 5 mg/kg IV q12h for 14-21 days, then valganciclovir 900 mg PO q24h
PLUS
Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14-21 days; then 90-120 mg/kg IV q24h.
Epstein-Barr virus
Preferred Regimen
Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day[8]
May be beneficial, however potential risks must be considered.
Human herpesvirus 6
Preferred Regimen
Ganciclovir 5 mg/kg IV q12h for 14-21 days
Alternative Regimen
Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14-21 days; then 90-120 mg/kg IV q24h.
Used in immunocompromised patients; no good data on effectiveness in immunocompetent patients.
B virus
Postexposure prophylaxis
Valacyclovir 1 gm PO q8h, for 14 days
OR
Acyclovir 800 mg PO 5x/day, for 14 days
Treatment of disease (Absent CNS symptoms)
Ganciclovir 5 mg/kg IV q12h
OR
Acyclovir 12.5-15 mg/kg IV q8h
Treatment of disease (Presenting CNS symptoms)
Ganciclovir 5 mg/kg IV q12h
Influenza virus
Preferred Regimen
Oseltamivir 75 mg/day, for at least 10 days
Measles virus
Preferred Regimen
Ribavirin
Consider intrathecal ribavirin in patients with subacute sclerosing panencephalitis
Nipah virus
Preferred Regimen
Ribavirin
West Nile virus
Preferred Regimen
Ribavirin is not recommended
Japanese encephalitis virus
Preferred Regimen
IFN-α is not recommended
St. Louis encephalitis virus
Preferred Regimen
IFN-2α
HIV
Preferred Regimen
HAART
JC virus
Preferred Regimen
▸ Reversal of immunosuppression
OR
HAART
In HIV-infected patients

Pathogen-Based Therapy — Bacteria [9] [3]

▸ Click on the following categories to expand treatment regimens.

Bacteria

  ▸  Bartonella bacilliformis

  ▸  Bartonella henselae

  ▸  Listeria monocytogenes

  ▸  Mycoplasma pneumoniae

  ▸  Tropheryma whipplei

Mycobacteria

  ▸  Mycobacterium tuberculosis

Rickettsioses and ehrlichioses

  ▸  Anaplasma phagocytophilum

  ▸  Ehrlichia chaffeensis

  ▸  Rickettsia rickettsii

  ▸  Coxiella burnetii

Spirochetes

  ▸  Borrelia burgdorferi

  ▸  Treponema pallidum

Bartonella bacilliformis
Preferred Regimen
Chloramphenicol50 mg/kg/day IV q6h. Resistant strains might require up to 100 mg/kg/day
Alternative Regimen
Ciprofloxacin 500 mg PO q12h
OR
Doxycycline 100 mg/day PO q12h
OR
Ampicillin 250-500 mg/day PO q6h
OR
Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h
Bartonella henselae
Preferred Regimen
Azithromycin Adults: 500 mg PO, 1x, then 250 mg/day PO for 4 days; Children: 10 mg/kg 1x, then 5 mg/kg/day PO for 4 days
Alternative Regimen
Doxycycline 100 mg PO 2x/day for 8 weeks
With or without Rifampin 300 mg PO 2x/day.
Listeria monocytogenes
Preferred Regimen
Ampicillin 250-500 mg PO q6h or 1-2 g IV/IM q4-6h
PLUS
Gentamicin 1-2.5 mg/kg/dose IV/IM q8-12h
Alternative Regimen
Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h
In the penicillin-allergic patient
Mycoplasma pnumoniae
Preferred Regimen
Azithromycin 500 mg PO once, then 250 mg 1x/day, for 4 days
Alternative Regimen
Doxycycline 200 mg/day BID PO or IV 1x/day, then 100-200 mg/day qDay or divided q12h PO/IV
OR
Fluoroquinolone 500 mg PO/IV 1x/day, for 7-14 days or 750 mg PO/IV 1x/day, for 5 days
Tropheryma whipplei
Preferred Regimen
Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days
PLUS
Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h
OR
Cefixime 400 mg/day PO 1x/day or divided q12h
Mycobacterium tuberculosis
Preferred Regimen
Isoniazid 300 mgPO qDay, for 9 months
PLUS
Rifampin 10 mg/kg/day PO or 10 mg/kg PO 2x/week (do not exceed 600 mg/day) (DOT)
PLUS
Ethambutol 15 mg/kg PO qDay
PLUS
Pyrazinamide 15-30 mg/kg PO qDay; not exceeding 2 g/day or 50 mg/kg PO 2x/weekly, not exceeding 2 g/dose
PLUS
Dexamethasone 10mg IV q6h
Add in patients with meningitis
Anaplasma phagocytophilum
Preferred Regimen
Doxycycline 100 mg PO 2x/day for 30-60 days
Ehrlichia chaffeensis
Preferred Regimen
Doxycycline 100 mg PO 2x/day for 30-60 days
Rickettsia rickettsii
Preferred Regimen
Doxycycline 100 mg PO 2x/day for 30-60 days
Alternative Regimen
Chloramphenicol 50 mg/kg/day IV divided q6hr
In certain clinical scenarios (pregnancy)
Coxiella burnetii
Preferred Regimen
Doxycycline 100 mg PO 2x/day for 30-60 days
PLUS
Fluoroquinolone 500 mg PO q12h or 400 mg IV q12h for 10 days
PLUS
Rifampin 600 mg q12hr for 2 days
Borrelia burgdorferi
Preferred Regimen
Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days
OR
Cefotaxime 2 g IV q4h, up to 12 g/day
OR
Penicillin G benzathine 2.4 million units/4mL syringe IM qWeek x3 [10]
Treponema pallidum
Preferred Regimen
Penicillin G benzathine 2.4 million units/4mL syringe IM qWeek x3 [10]
Alternative Regimen
Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days

Pathogen-Based Therapy — Fungi, Protozoa and Helminths [11] [3]

▸ Click on the following categories to expand treatment regimens.

Fungi

  ▸  Coccidioides species

  ▸  Cryptococcus neoformans

  ▸  Histoplasma capsulatum

Protozoa

  ▸  Acanthamoeba

  ▸  Balamuthia mandrillaris

  ▸  Naegleria fowleri

  ▸  Plasmodium falciparum

  ▸  Toxoplasma gondii

  ▸  Trypanosoma brucei gambiense

  ▸  Trypanosoma brucei rhodesiense

Helminths

  ▸  Baylisascaris procyonis

  ▸  Gnathostoma species

  ▸  Taenia solium

Coccidioides species
Preferred Regimen
Fluconazole 400 mg PO on day 1, followed by 200 mg PO qDay
Alternative Regimen
Itraconazole 200 mg PO q8hr for 3-4 days, followed by 200-400 mg/day for at least 3 months
OR
Voriconazole 6 mg/kg IV q12hr for 24 hours, followed by 4 mg/kg IV q12hr or 200 mg PO q12hr
OR
Amphotericin B (IV or Intratechal) start with load dose: 0.25-0.5 mg/kg IV infused over 2-6h, followed by maintenance dose: 0.25-1 mg/kg IV qDay
Cryptococcus neoformans
Preferred Regimen
Amphotericin B start with load dose: 0.25-0.5 mg/kg IV infused over 2-6h, followed by maintenance dose: 0.25-1 mg/kg IV qDay
PLUS
Flucytosine 50-150 mg/kg/day PO divided q6hr
Alternative Regimen
Lipid formulation of amphotericin B 6 mg/kg IV qDay
PLUS
Flucytosine 50-150 mg/kg/day PO divided q6hr
Histoplasma capsulatum
Preferred Regimen
Liposomal Amphotericin B 6 mg/kg IV qDay
PLUS
Itraconazole 200 mg PO q8hr for 3-4 days, followed by 200-400 mg/day for at least 3 months
Acanthamoeba
Preferred Regimen
Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h
PLUS
Rifampin 600 mg q12hr for 2 days
PLUS
Ketoconazole 200-400 mg/day PO
Alternative Regimen
Fluconazole 400 mg PO on Day 1, then 200 mg PO qDay
PLUS
Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO)
PLUS
Pyrimethamine 50-75 mg qDay PO, for 1-3 weeks; then 25-37.5 mg qDay PO for 4-5 weeks
Balamuthia mandrillaris
Preferred Regimen
Pentamidine 2-4 mg/kg IM q24-48hr
PLUS
Macrolide (Azithromycin 500 mg PO once, then 250 mg once daily; or Clarithromycin 500 mg PO q12hr)
PLUS
Fluconazole 400 mg PO on Day 1, then 200 mg PO qDay
PLUS
Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO)
PLUS
Flucytosine 50-150 mg/kg/day PO divided q6hr
PLUS
Phenothiazine
Naegleria fowleri
Preferred Regimen
Amphotericin B 1.5 mg/kg/day IV divided in 2 doses, for 3 days; then 1 mg/kg/day for 6 days + 1.5 mg/day intrathecal for 2 days; then 1 mg/day intrathecal for 8 days
PLUS
Rifampin 600 mg q12hr for 2 days
Plasmodium falciparum
Preferred Regimen
Quinine 648 mg PO q8hr, for 3-7 days
OR
Quinidine 300-600 mg or 10 mg/kg PO q8hr, for 5-7 days
OR
Artemether Administer 24 tablets over 3 days: Day 1: 4 tablets initially and 4 tablets after 8h; Day 2 and 3: 4 tablets 2x/day (1 tablet= 20mg/120mg)
Alternative Regimen
Atovaquone-proguanil 1 g/400 mg PO daily, for 3 days
Exchange transfusion recommended for patients with cerebral malaria or more than 10% parasitemia.
Toxoplasma gondii
Preferred Regimen
Pyrimethamine 50-75 mg qDay PO for 1-3 weeks, then 25-37.5 mg qDay PO for 4-5 weeks
PLUS
Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO)
OR
Clindamycin 300 mg PO 4x/day, for 6 weeks
Alternative Regimen
Trimethoprim 10 mg/kg/day - Sulfametoxazole 50 mg/kg/day, for 4 weeks
OR
Pyrimethamine 100mg loading dose PO followed by 25-50 mg/day, for 6 weeks
PLUS
Atovaquone 750 mg 2x/day, for 6 weeks
OR
Clarithromycin 500 mg PO q12hr
OR
Azithromycin 500 mg/day, for 6 weeks
OR
Dapsone 100 mg PO qDay
Trypanosoma brucei gambiense
Preferred Regimen
Eflornithine 400 mg/kg/day IV divided 4x/day, for 14 days, then 300 mg/kg/day PO, for 3-4 weeks
Alternative Regimen
Melarsoprol 2-3.6 mg/kg/day IV, for 3 days; after 1 week: 3.6 mg/kg/day IV, for 3 days; then repeat again after 10-21 days: 3.6 mg/kg/day
Trypanosoma brucei rhodesiense
Preferred Regimen
Melarsoprol 2-3.6 mg/kg/day IV for 3 days; then repeat after 7 days; then repeat for 3rd time, 7 days after the 2nd course
Baylisascaris procyonis
Preferred Regimen
Albendazole 400 mg PO x1 day
PLUS
Diethycarbamazine
Consider adjunctive corticosteroids
Gnathostoma species
Preferred Regimen
Albendazole 400 mg PO q24h or twice a day, for 21 days
OR
Ivermectin 200 μg/kg/day PO, for 2 days
Taenia solium
Preferred Regimen
Albendazole (more than 60 kgs) 400 mg PO 2x/day, for 8-30 days; (less than 60 kg) 15 mg/kg/day PO divided 2x/day, for 8-30 days; no more than 800 mg/day
PLUS
Corticosteroids
Alternative Regimen
Praziquantel 10-20 mg/kg x1
Evaluate need for treatment

Pathogen-Based Therapy — Postinfectious or Postvaccination status [12] [3]

▸ Click on the following categories to expand treatment regimens.

Postinfectious/postvaccination status

  ▸  Acute disseminated encephalomyelitis

Acute Disseminated Encephalomyelitis
Preferred Regimen
High dose Corticosteroids
Alternative Regimen
Plasma exchange
OR
Intravenous immunoglobulin

Follow Up Therapy

  • Physiotherapy
  • Occupational therapy
  • Speech therapy
  • Psychotherapy


References

  1. Whitley RJ (1990). "Viral encephalitis". The New England Journal of Medicine. 323 (4): 242–50. doi:10.1056/NEJM199007263230406. PMID 2195341. Retrieved 2012-02-14. Unknown parameter |month= ignored (help)
  2. Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.
  3. 3.0 3.1 3.2 3.3 3.4 Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL; et al. (2008). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clin Infect Dis. 47 (3): 303–27. doi:10.1086/589747. PMID 18582201.
  4. russ. Drug pocket 2011/12 (9th edition ed.). Börm Bruckmeier Publishing. ISBN 978-1-59103-258-8.
  5. Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.
  6. russ. Drug pocket 2011/12 (9th edition ed.). Börm Bruckmeier Publishing. ISBN 978-1-59103-258-8.
  7. russ. Drug pocket 2011/12 (9th edition ed.). Börm Bruckmeier Publishing. ISBN 978-1-59103-258-8.
  8. russ. Drug pocket 2011/12 (9th edition ed.). Börm Bruckmeier Publishing. ISBN 978-1-59103-258-8.
  9. Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.
  10. 10.0 10.1 Swett C (1975). "Outpatient phenothiazine use and bone marrow depression. A report from the drug epidemiology unit and the Boston collaborative drug surveillance program". Arch Gen Psychiatry. 32 (11): 1416–8. PMID 978-1-59103-258-8 Check |pmid= value (help).
  11. Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.
  12. Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.

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