Sandbox g23

Encephalitis

• Empiric antimicrobial therapy

• Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days

Note (1): Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies.

Note (2): Other empiric antimicrobial agents should be administered on the basis of specific epidemiologic or clinical clues.

• Specific epidemiologic considerations

• Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
• Age

• Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
• Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
• Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes

• Animal contact

• Bats — Rabies virus, Nipah virus
• Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
• Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
• Dogs — Rabies virus
• Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
• Old World primates — B virus
• Raccoons — Rabies virus, Baylisascaris procyonis
• Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
• Sheep and goats — C. burnetii
• Skunks — Rabies virus
• Swine — Japanese encephalitis virus, Nipah virus
• White-tailed deer — Borrelia burgdorferi

• Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii

• Ingestion

• Raw or partially cooked meat — T. gondii
• Raw meat, fish, or reptiles — Gnanthostoma species
• Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii

• Insect contact

• Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
• Sandflies — Bartonella bacilliformis
• Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
• Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense

• Occupation

• Exposure to animals — Rabies virus, C. burnetii, Bartonella species
• Exposure to horses — Hendra virus
• Exposure to Old World primates — B virus
• Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
• Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
• Veterinarians — Rabies virus, Bartonella species, C. burnetii

• Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum

• Recent vaccination — Acute disseminated encephalomyelitis

• Recreational activities

• Camping/hunting — Agents transmitted by mosquitoes and ticks
• Sexual contact — HIV, T. pallidum
• Spelunking — Rabies virus, H. capsulatum
• Swimming — Enteroviruses, Naegleria fowleri

• Season

• Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
• Winter — Influenza virus

• Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii

• Travel

• Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
• Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
• Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
• Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
• India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
• Middle East — West Nile virus, P. falciparum
• Russia — Tickborne encephalitis virus
• South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
• Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
• Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus

• Specific clinical considerations

• General findings

• Hepatitis — Coxiella burnetii
• Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
• Parotitis — Mumps virus
• Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
• Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
• Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
• Urinary symptoms — St. Louis encephalitis virus

• Neurologic findings

• Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
• Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
• Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
• Myorhythmia — T. whipplei (oculomasticatory)
• Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
• Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
• Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes

• Pathogen-directed antimicrobial therapy

• Viruses

• Adenovirus

• Preferred regimen: supportive

• B virus (herpes B virus)

• Established disease

• Preferred regimen: Valacyclovir 1,000 mg PO tid OR Ganciclovir 5 mg/kg IV q12h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily indefinitely OR Valacyclovir 1 g PO tid indefinitely
• Alternative regimen: Acyclovir 15 mg/kg IV q8h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily OR Valacyclovir 1 g PO tid indefinitely

• Prophylaxis after bite or scratch

• Preferred regimen: Valacyclovir 1,000 mg PO tid

• Cytomegalovirus (CMV)

• Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance AND Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance

• Eastern equine encephalitis virus

• Preferred regimen: supportive

• Epstein-Barr virus (EBV)

• Preferred regimen: supportive ± Corticosteroids

Note: Acyclovir is not recommended.

• Hendra virus

• Preferred regimen: supportive

• HSV-1 and HSV-2

• Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
• Preferred regimen (neonates): Acyclovir 20 mg/kg IV q8h for 21 days

• Human herpesvirus 6 (HHV-6)

• Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance OR Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance

• Human immunodeficiency virus (HIV)

• Preferred regimen: HAART

• Influenza virus

• Preferred regimen: Oseltamivir 75 mg PO bid

• Japanese encephalitis virus

• Preferred regimen: supportive

Note: Interferon alpha is not recommended.

• JC virus

• Preferred regimen: Reversal or control of immunosuppression OR HAART in patients with AIDS

• La Crosse virus

• Preferred regimen: supportive

• Measles virus

• Life-threatening disease

• Preferred regimen: Ribavirin

• SSPE

• Preferred regimen: Ribavirin intrathecal

• Mumps virus

• Preferred regimen: supportive

• Murray Valley encephalitis virus

• Preferred regimen: supportive

• Nipah virus

• Preferred regimen: supportive

• Alternative regimen: Ribavirin

• Nonpolio enteroviruses

• Preferred regimen: supportive

Note: Consider intraventricular γ-globulin for chronic and/or severe disease.

• Poliovirus

• Preferred regimen: supportive

• Powassan virus

• Preferred regimen: supportive

• Rabies virus

• Preferred regimen: supportive

Note: Administer rabies immunoglobulin and vaccination for postxposure prophylaxis.

• Rubella virus

• Preferred regimen: supportive

• St. Louis encephalitis virus

• Preferred regimen: supportive
• Alternative regimen: IFN-α-2b

• Tickborne encephalitis virus

• Preferred regimen: supportive

• Vaccinia

• Preferred regimen: supportive ± Corticosteroids (if suggestive of post-immunization)

• Venezuelan equine encephalitis virus

• Preferred regimen: supportive

• Varicella zoster virus (VZV)

• Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 10–14 days ± Corticosteroids
• Alternative regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance ± Corticosteroids

• West Nile virus

• Preferred regimen: supportive

• Western equine encephalitis virus

• Preferred regimen: supportive

• Bacteria

• Anaplasma phagocytophilum (human granulocytotrophic ehrlichiosis)

• Preferred regimen: Doxycycline

• Bartonella bacilliformis (Oroya fever, Carrion's disease)

• Preferred regimen: Chloramphenicol OR Ciprofloxacin] OR Doxycycline OR Ampicillin OR Trimethoprim-Sulfamethoxazole

• Bartonella henselae (cat scratch disease)

• Preferred regimen: Doxycycline OR Azithromycin ± Rifampin

• Borrelia burgdorferi (Lyme disease)

• Preferred regimen: Ceftriaxone OR Cefotaxime OR Penicillin G

• Coxiella burnetii (Q fever)

• Preferred regimen: Doxycycline AND Fluoroquinolone AND Rifampin

• Ehrlichia chaffeensis (human monocytotrophic ehrlichiosis)

• Preferred regimen: Doxycycline

• Listeria monocytogenes

• Preferred regimen: Ampicillin AND Gentamicin
• Alternative regimen: Trimethoprim-Sulfamethoxazole

• Mycobacterium tuberculosis

• Preferred regimen: (Isoniazid AND Rifampin AND Pyrazinamide AND Ethambutol) ± Dexamethasone (if suggestive of meningitis)

• Mycoplasma pneumoniae

• Preferred regimen: Azithromycin OR Doxycycline OR Fluoroquinolone

• Rickettsia rickettsii (Rocky Mountain spotted fever)

• Preferred regimen: Doxycycline
• Alternative regimen: Chloramphenicol (for pregnant patients)

• Treponema pallidum (syphilis)

• Preferred regimen: Penicillin G
• Alternative regimen: Ceftriaxone

• Tropheryma whipplei (Whipple's disease)

• Preferred regimen: Ceftriaxone for 2–4 weeks, followed by Trimethoprim-Sulfamethoxazole for 1–2 years OR Cefixime for 1–2 years

• Fungi

• Coccidioides

• Preferred regimen: Fluconazole
• Alternative regimen: Itraconazole OR Voriconazole OR Amphotericin B (intravenous and intrathecal)

• Cryptococcus neoformans

• Preferred regimen (1): Amphotericin B deoxycholate AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
• Preferred regimen (2): Amphotericin B lipid complex AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
• Preferred regimen (3): Amphotericin B deoxycholate AND Flucytosine for 6–10 weeks, followed by Fluconazole for 8 weeks

Note: Consider placement of lumbar drain or VP shunt.

• Histoplasma capsulatum

• Preferred regimen: Amphotericin B liposomal for 4–6 weeks, followed by Itraconazole for at least 1 year and until resolution of CSF abnormalities

• Protozoa

• Acanthamoeba

• Preferred regimen (1): Trimethoprim-Sulfamethoxazole AND Rifampin AND Ketoconazole
• Preferred regimen (2): Fluconazole AND Sulfadiazine AND Pyrimethamine

• Balamuthia mandrillaris

• Preferred regimen: (Azithromycin OR Clarithromycin) AND Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Thioridazine OR Trifluoperazine)

• Naegleria fowleri

• Preferred regimen: Amphotericin B (intravenous and intrathecal) AND Rifampin AND (Azithromycin OR Sulfisoxazole OR Miconazole)

• Plasmodium falciparum

• Preferred regimen: Quinine OR Quinidine OR Artesunate OR Artemether
• Alternative regimen (1): Atovaquone-Proguanil
• Alternative regimen (2): Exchange transfusion (for > 10% parasitemia or cerebral malaria)

• Toxoplasma gondii

• Preferred regimen: Pyrimethamine AND Sulfadiazine OR Clindamycin
• Alternative regimen (1): Trimethoprim-sulfamethoxazole
• Alternative regimen (2): Pyrimethamine AND (Atovaquone OR Clarithromycin OR Azithromycin OR Dapsone

• Trypanosoma brucei gambiense (West African trypanosomiasis)

• Preferred regimen: Eflornithine OR Melarsoprol

• Trypanosoma brucei rhodesiense (East African trypanosomiasis)

• Preferred regimen: Melarsoprol

• Helminths

• Baylisascaris procyonis

• Preferred regimen: Albendazole AND Diethylcarbamazine AND Corticosteroids

• Gnathostoma

• Preferred regimen: Albendazole OR Ivermectin

• Taenia solium (cysticercosis)

• Preferred regimen: Albendazole AND Corticosteroids
• Alternative regimen: Praziquantel AND Corticosteroids

• Prion

• Human transmissible spongiform encephalopathy

• Preferred regimen: supportive