This is the current release of the guideline.

Definitions of the quality of evidence (I-III) and strength of recommendation (A-C) are repeated at the end of the 'Major Recommendations' field.

Etiology

1. Epidemiologic clues and assessment of risk factors to identify potential etiologic agents should be sought in all patients with encephalitis (See Table 2 in the original guideline document) (A-III).
2. Clinical clues (general and specific neurologic findings) may be helpful in suggesting certain causative agents in patients with encephalitis (See Table 3 in the original guideline document) (B-III).
3. In patients with encephalitis and a history of recent infectious illness or vaccination, the diagnosis of acute disseminated encephalomyelitis (ADEM) should be considered (B-III).

Diagnosis

4. Specific diagnostic studies should be performed for the majority of patients who present with encephalitis (See Table 4 in the original guideline document) (A-III).
5. Additional diagnostic studies should be performed for patients with encephalitis on the basis of specific epidemiologic and clinical clues (See Tables 2, 3 and 5 in the original guideline document) (A-III).

Diagnostic Studies Outside the Central Nervous System (CNS)

6. Cultures of body fluid specimens (e.g., from blood, stool, nasopharynx, or sputum), if clinical and epidemiologic clues are suggestive, should be performed in an attempt to identify various viral, bacterial and fungal etiologies of encephalitis (see Table 5 in the original guideline document) (B-III); positive results do not necessarily indicate that the isolated microorganism is the etiology of encephalitis and must be interpreted in the context of the appropriate epidemiologic findings, clinical findings, and other diagnostic study results.
7. Biopsy of specific tissues for culture, antigen detection, nucleic acid amplification tests (such as polymerase chain reaction (PCR), and histopathologic examination should be performed in an attempt to establish an etiologic diagnosis of encephalitis (See Table 5 in the original guideline document) (A-III).
8. Certain causes of encephalitis may be diagnosed by detection of immunoglobulin M (IgM) antibodies in serum (See Table 5 in the original guideline document) (A-III).
9. Although acute- and convalescent-phase serum samples are generally not useful in establishing the etiology during the acute presentation in a patient with encephalitis, they may be useful for the retrospective diagnosis of an infectious agent (See Table 5 in the original guideline document) (B-III).
10. Nucleic acid amplification tests (such as PCR) of body fluids outside of the CNS may be helpful in establishing the etiology in some patients with encephalitis (See Table 5 in the original guideline document) (B-III).

Neurodiagnostic Studies

11. Magnetic resonance imaging (MRI) is the most sensitive neuroimaging test to evaluate patients with encephalitis (A-I).
12. Computed tomography (CT), with and without contrast enhancement, should be used to evaluate patients with encephalitis if MRI is unavailable, impractical, or cannot be performed (B-III).
13. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is not routinely recommended for patients with encephalitis.
14. Electroencephalography (EEG) is rarely helpful in establishing an etiology in patients with encephalitis, but it has a role in identifying patients with nonconvulsive seizure activity who are confused, obtunded, or comatose and should be performed in all patients with encephalitis (A-III).
15. Cerebrospinal fluid (CSF) analysis is essential (unless contraindicated) in all patients with encephalitis (A-III).

Diagnostic Studies in the CNS

16. For certain viral agents, the presence of virus-specific IgM in CSF specimens may be indicative of CNS disease caused by that pathogen (See Table 5 in the original guideline document) (A-III).
17. Nucleic acid amplification tests (such as PCR) should be performed on CSF specimens to identify certain etiologic agents in patients with encephalitis (See Table 5 in the original guideline document) (A-III). Although a positive test result is helpful in diagnosing infection caused by a specific pathogen, a negative result cannot be used as definitive evidence against the diagnosis.
18. Herpes simplex PCR should be performed on all CSF specimens in patients with encephalitis (A-III). In patients with encephalitis who have a negative herpes simplex PCR result, consideration should be given to repeating the test 3–7 days later in those with a compatible clinical syndrome or temporal lobe localization on neuroimaging (B-III).
19. Viral cultures of CSF specimens are of limited value in patients with encephalitis and are not routinely recommended.
20. Brain biopsy should not be routinely used in patients with encephalitis but should be considered in patients with encephalitis of unknown etiology whose condition deteriorates despite treatment with acyclovir (B-III).

Treatment

Empirical Therapy

21. Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies (AIII).
22. Other empirical antimicrobial agents should be initiated on the basis of specific epidemiologic or clinical factors (See Tables 2 & 3 in the original guideline document), including appropriate therapy for presumed bacterial meningitis, if clinically indicated (A-III).
23. In patients with clinical clues suggestive of rickettsial or ehrlichial infection during the appropriate season, doxycycline should be added to empirical treatment regimens (A-III).

Specific Therapy

Viruses

24. Herpes simplex virus: acyclovir is recommended (AI).
25. Varicella-zoster virus: acyclovir is recommended (BIII); ganciclovir can be considered an alternative (C-III); adjunctive corticosteroids can be considered (C-III).
26. Cytomegalovirus: the combination of ganciclovir plus foscarnet is recommended (B-III); cidofovir is not recommended, because its ability to penetrate the blood-brain barrier has been poorly studied.
27. Epstein-Barr virus: acyclovir is not recommended; the use of corticosteroids may be beneficial (C-III), but the potential risks must be weighed against the benefits.
28. Human herpesvirus 6: ganciclovir or foscarnet should be used in immunocompromised patients (B-III); use of these agents in immunocompetent patients can be considered (CIII), but there are not good data on their effectiveness.
29. B virus: valacyclovir is recommended (B-III); alternative agents are ganciclovir (B-III) and acyclovir (C-III).
30. Influenza virus: oseltamivir can be considered (C-III).
31. Measles virus: ribavirin can be considered (C-III); intrathecal ribavirin can be considered in patients with subacute sclerosing panencephalitis (C-III).
32. Nipah virus: ribavirin can be considered (C-III).
33. West Nile virus: ribavirin is not recommended.
34. Japanese encephalitis virus: interferon alfa (IFN-alfa) is not recommended.
35. St. Louis encephalitis virus: IFN-2alfa can be considered (C-III).
36. Human immunodeficiency virus (HIV): highly active antiretroviral therapy (HAART) is recommended (A-II).
37. John Cunningham (JC) virus: reversal of immunosuppression (A-III)—or HAART in HIV-infected patients (A-II)—is recommended.

Bacteria

38. Bartonella bacilliformis: chloramphenicol, ciprofloxacin, doxycycline, ampicillin, or trimethoprim-sulfamethoxazole is recommended (B-III).
39. Bartonella henselae: doxycycline or azithromycin, with or without rifampin, can be considered (C-III).
40. Listeria monocytogenes: ampicillin plus gentamicin is recommended (A-III); trimethoprim-sulfamethoxazole is an alternative in the penicillin-allergic patient (A-III).
41. Mycoplasma pneumoniae: antimicrobial therapy (azithromycin, doxycycline, or a fluoroquinolone) can be considered (C-III).
42. Tropheryma whipplei: ceftriaxone, followed by either trimethoprim-sulfamethoxazole or cefixime, is recommended (B-III).

Mycobacteria

43. Mycobacterium tuberculosis: 4-drug antituberculous therapy should be initiated (A-III); adjunctive dexamethasone should be added in patients with meningitis (B-I).

Rickettsioses and Ehrlichioses

44. Anaplasma phagocytophilum: doxycycline is recommended (A-III).
45. Ehrlichia chaffeensis: doxycycline is recommended (AII).
46. Rickettsia rickettsii: doxycycline is recommended (AII); chloramphenicol can be considered an alternative in selected clinical scenarios, such as pregnancy (C-III).
47. Coxiella burnetii: doxycycline plus a fluoroquinolone plus rifampin is recommended (B-III).

Spirochetes

48. Borrelia burgdorferi: ceftriaxone, cefotaxime, or penicillin G is recommended (B-II).
49. Treponema pallidum: penicillin G is recommended (A-II); ceftriaxone is an alternative (B-III).

Fungi

50. Coccidioides species: fluconazole is recommended (A-II); alternatives are itraconazole (B-II), voriconazole (B-III), and amphotericin B (intravenous and intrathecal) (C-III).
51. Cryptococcus neoformans: initial treatment with amphotericin B deoxycholate plus flucytosine (A-I) or a lipid formulation of amphotericin B plus flucytosine (A-II) is recommended.
52. Histoplasma capsulatum: liposomal amphotericin B followed by itraconazole is recommended (B-III)

Protozoa

53. Acanthamoeba: trimethoprim-sulfamethoxazole plus rifampin plus ketoconazole (C-III) or fluconazole plus sulfadiazine plus pyrimethamine (C-III) can be considered.
54. Balamuthia mandrillaris: pentamidine, combined with a macrolide (azithromycin or clarithromycin), fluconazole, sulfadiazine, flucytosine, and a phenothiazine can be considered (C-III).
55. Naegleria fowleri: amphotericin B (intravenous and intrathecal) and rifampin, combined with other agents, can be considered (C-III).
56. Plasmodium falciparum: quinine, quinidine, or artemether is recommended (A-III); atovaquone-proguanil is an alternative (B-III); exchange transfusion is recommended for patients with 10% parasitemia or cerebral malaria (B-III); corticosteroids are not recommended.
57. Toxoplasma gondii: pyrimethamine plus either sulfadiazine or clindamycin is recommended (A-I); trimethoprim-sulfamethoxazole alone (B-I) and pyrimethamine plus either atovaquone, clarithromycin, azithromycin, or dapsone (B-III) are alternatives.
58. Trypanosoma brucei gambiense: eflornithine is recommended (A-II); melarsoprol is an alternative (A-II).
59. Trypanosoma brucei rhodesiense: melarsoprol is recommended (A-II).

Helminths

60. Baylisascaris procyonis: albendazole plus diethylcarbamazine can be considered (C-III); adjunctive corticosteroids should also be considered (B-III).
61. Gnathostoma species: albendazole (B-III) or ivermectin (B-III) is recommended.
62. Taenia solium: need for treatment should be individualized; albendazole and corticosteroids are recommended (B-III); praziquantel can be considered as an alternative (C-II).

Postinfectious/Postvaccination Status

63. Acute disseminated encephalomyelitis: high-dose corticosteroids are recommended (B-III); alternatives include plasma exchange (B-III) and intravenous immunoglobulin (C-III).

Definitions:

Quality of Evidence

1. Evidence from >1 properly randomized, controlled trial
2. Evidence from >1 well-designed clinical trial, without randomization; from cohort or case-controlled analytical studies (preferably from >1 center); from multiple time-series; or from dramatic results from uncontrolled experiments
3. Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Strength of Recommendation

1. Good evidence to support a recommendation for use
2. Moderate evidence to support a recommendation for use
3. Poor evidence to support a recommendation

None provided

The type of supporting evidence is identified and graded for most recommendations (see the "Major Recommendations" field).

Not applicable: The guideline was not adapted from another source.

2008 Aug 1

Infectious Diseases Society of America - Medical Specialty Society

Infectious Diseases Society of America (IDSA)

Infectious Diseases Society of America (IDSA) Practice Guidelines Committee

Authors: Allan R. Tunkel, Monmouth Medical Center, Long Branch, New Jersey; Carol A. Glaser, California Department of Health Services, Richmond; Karen C. Bloch, Vanderbilt University School of Medicine, Nashville, Tennessee; James J. Sejvar, Centers for Disease Control and Prevention, Atlanta, Georgia; Christina M. Marra, University of Washington School of Medicine, Seattle; Karen L. Roos, Indiana University School of Medicine, Indianapolis; Barry J. Hartman, Weill Cornell Medical Center, New York, New York; Sheldon L. Kaplan, Baylor College of Medicine, Houston, Texas; W. Michael Scheld, University of Virginia School of Medicine, Charlottesville; Richard J. Whitley, University of Alabama at Birmingham

All members of the panel complied with the Infectious Diseases Society of America policy on conflicts of interest, which requires disclosure of any financial or other interest that might be construed as constituting an actual, potential, or apparent conflict. Members of the panel were provided with the Infectious Diseases Society of America conflict of interest disclosure statement and were asked to identify ties to companies developing products that might be affected by promulgation of the guideline. Information was requested regarding employment, consultancies, stock ownership, honoraria, research funding, expert testimony, and membership in company advisory committees. The panel made decisions on a case-by-case basis as to whether an individual's role should be limited as a result of conflict. No limiting conflicts were identified.

S.L.K. received investigator-initiated grants from Pfizer, Wyeth, and Sanofi-Pasteur and served on the advisory board for Pfizer. All other authors: no conflicts.

This is the current release of the guideline.

None available

This NGC summary was completed by ECRI Institute on June 10, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.