Guidelines on the management of infectious …

1 Disponible en ligne decine et maladies infectieuses 47 (2017) 179 194 Recommendations/RecommandationsGuideline s on the management of infectious encephalitis in adultsRecommandations de prise en charge des enc phalites infectieuses de l Stahla, ,1, P. Azouvib, F. Bruneelc, T. De Brouckerd, X. Duvale, B. Fantinf, N. Girardg, Herrmannh, J. Honnorati, M. Lecuitj,k, A. Maillesl,1,L. Martinez-Almoynam, P. Morandn, L. Pirotho, P. Tattevinp,1, The reviewing group2aInfectiologie, universit et CHU Grenoble Alpes, 38700 La Tronche, FrancebR habilitation neurologique, centre hospitalier de Garches, 92380 Garches, FrancecService de r animation, centre hospitalier de Versailles, 78150 Le Chesnay, FrancedNeurologie, centre hospitalier de Saint-Denis, 93200 Saint-Denis, FranceeTh rapeutique, CHU Bichat, 75018 Paris, FrancefIAME, UMR 1137, Inserm, m decine interne, h pital Beaujon, universit Paris Diderot, Sorbonne Paris Cit , AP HP, 75013 Paris, FrancegNeuroradiologie, h pital La Timone, 13385 Marseille, FrancehMicrobiologie, h pital Raymond-Poincar , 92380 Garches, FranceiNeurologie, h pital neurologique, CHU de Lyon, 69002 Lyon, FrancejUnit de biologie des infections, institut Pasteur, CNR et CCOMS Listeria, Inserm U1117, 75015 Paris, FrancekDepartment of infectious diseases and tropical medicine, institut imagine.

2 Paris Descartes university, Sorbonne Paris Cit , Necker-Enfants Malades universityhospital, Assistance publique H pitaux de Paris, 75015 Paris, FrancelDirection des maladies infectieuses, sant publique, 94415 Saint-Maurice, FrancemNeurologie, h pital Nord, 13015 Marseille, FrancenVirologie, universit et CHU Grenoble Alpes, 38700 La Tronche, FranceoInfectiologie, CHU de Dijon, 21000 Dijon, FrancepInfectiologie, CHU de Rennes, 35000 Rennes, FranceReceived 18 January 2017; accepted 19 January 2017 Available online 12 April 2017 The literature analysis group included the following individ-uals:Anne Bertrand (Radiology, Piti -Salp tri re, Paris), AnneBoucher ( infectious diseases, CHU de Lille), Rodolphe Buz l (Internal medicine, Paris), Yoan Crabol (Internal medicine, CHVannes-Auray), Pierre Fillatre ( infectious diseases, CHU deRennes), Tiphaine Goulenok (Internal medicine, Paris).These Clinical Practice Guidelines were drafted under thesupervision of the French infectious Diseases Society (Frenchacronym SPILF), in partnership with the following scientificsocieties: Corresponding address: ( Stahl).

3 1 Members of the European study Group for the Infections of the brain (ESGIB).2 The Reviewing group includes: F. Bourdain, D. Boutolleau, E. Denes,A. Friggeri, A. Lefort Des Ylouzes, S. Legriel, N. Lemaitre, J. Poissy, R. Son-neville, C. Tranchant, V. Zarrouk. National educational association for teaching therapeutics(French acronym APNET); French Society of Internal Medicine (French acronymSNFMI); French Federation of Neurology (French acronym FFN); French Intensive Care Society (French acronym SRLF); French Society of Anesthesia and Intensive Care (Frenchacronym SFAR); French Society of Microbiology (French acronym SFM); French Society of Neuroradiology (French acronym SFNR); French Society of Physical and Rehabilitation Medicine(French acronym SOFMER); French Society of Neurology (French acronym SFN).English versionThe SPILF Guidelines Committee commissioned a scien-tific committee to define questions that should be asked 2017 Elsevier Masson SAS.

4 All rights Stahl et al. / M decine et maladies infectieuses 47 (2017) 179 194managing infectious encephalitis patients, and answers to thesequestions in light of literature data. To determine the compo-sition of this scientific committee, each scientific society wasasked to appoint at least one representative who would sit on of the literature analysis group independently ana-lyzed the French and English literature. Each member wasassigned one of the questions defined by the scientific commit-tee. Their work aimed to be as comprehensive as possible andis published in a separate reviewing group was also set up; members worked in com-plete independence from the scientific committee. Reviewersassessed answers given to the questions, and rated them on ascale from 1 (strongly disagree) to 5 (strongly agree). Review-ers had the possibility to associate comments to their assessmentto explain the rates of any specific cases; however, rates lowerthan 3 had to be of the scientific committee reviewed and synthe-sized, all together, all comments and inserted them into the question was thus associated with a graded ratio-nale (1 = high level of evidence; 3 = low level of evidence) anda recommendation (A = strong recommendation; D = negativerecommendation: Physicians should not.)

5 1. Q1: When should acute infectious encephalitis beconsidered and how should it be confirmed? Clinical signs and RationaleLevel 1: the most common signs and symptoms of centralnervous system (CNS) dysfunction are: consciousness disorders (from clouded sensorium to coma); behavior disorders; seizures; focal neurological 1: symptoms of meningitis may be 1: fever is very common, but may be absent because ofantipyretic drug RecommendationsGrade A: physicians must look for any occurrence of feverin the days prior to the infection onset through the patient s andrelatives A: any signs or symptoms of CNS dysfunction asso-ciated with fever must lead physicians to consider infectiousencephalitis in the differential Biological RationaleLevel 1: no blood laboratory result is indicative of encephali-tis, but laboratory results may guide the etiological diagnosisand are needed to establish a differential 1: HIV primary infection may present as RecommendationsGrade A: two pairs of blood cultures must be sampled beforeinitiating the antibiotic therapy.

6 Complete blood count, bloodelectrolytes, blood glucose level (performed at the same timeas the lumbar puncture), CRP test, liver function test (ASAT,ALAT, bilirubin, alkaline phosphatase), hemostasis evaluation,and CPK measurement are A: a combined HIV serological test (simultaneousdetection of HIV1/HIV2 antibodies and p24 antigen) is compul-sory. When a primary HIV infection is suspected, a viral RNAblood test (viral load) is recommended along with the Cerebrospinal fluid (CSF) RationaleLevel 1: the amount of CSF sampled must allow for diagnos-tic 1: CSF cell count is abnormal when > 4 nucleatedcells/mm3are 1: the ratio of one leukocyte per 800 red blood cells isindicative of traumatic puncture or subarachnoid 1: low levels of CSF glucose in adults refer to a CSFglucose level < 40% of simultaneous blood RecommendationsGrade A: the minimum amount of CSF sampled must be120 drops (1 drop amounts to approximately 50 L): 20 drops(1 mL) for biochemistry tests and 80 to 100 drops (4 to 5 mL)for microbiological and virological tests.

7 Part of the CSF mustbe kept (at +4 C and then, if possible, at 80 C) for additionalbiological tests (including tuberculosis diagnostic test).Grade A: a cytological test and total protein/glucose/lactatemeasurement must urgently be performed, as well as microbio-logical A: CSF glucose level must imperatively be combinedwith a concomitant blood glucose level test (capillary glycemiaby Dextrostix test or venous testing at best).Grade A: a CSF standard bacteriological test must be per-formed (including direct examination following Gram-stainingand culture).Grade A: herpes simplex virus (HSV), varicella zoster virus(VZV), and enterovirus PCR tests are A: Mycobacterium tuberculosis detection by culturemust be performed when previous PCR test results are negativeor in case of high suspicion (clinical or epidemiological). RationaleLevel 1: when the patient s condition allows it and when itcan be performed without any delay, the diagnostic benefit of abrain MRI is far superior to that of the Stahl et al.

8 / M decine et maladies infectieuses 47 (2017) 179 194 RecommendationsGrade A: when it can be performed, the brain MRI is thefirst-line imaging to A: the MRI must include FLAIR, diffusion, T2*, andT1 sequences with and without gadolinium as well as venousand arterial vascular A: when an emergency MRI cannot be performed, aCT-scan of the brain must immediately be performed (with andwithout injection).Grade A: for patients presenting with consciousness disor-ders, signs of localized deficits, or focal/generalized seizures, brain imaging must immediately be performed to rule out lum-bar puncture contraindication. The lumbar puncture must thenbe urgently performed considering the potential for A: when the lumbar puncture cannot be performed, Guidelines related to the empirical treatment of bacterial menin-gitis AND infectious encephalitis should be B: an EEG may be indicated to investigate seizures,status epilepticus, and consciousness Q2: What is the initial conduct to adopt (first48 hours)?

9 Where should patients presenting with confirmed orsuspected encephalitis be hospitalized? RationaleLevel 1: encephalitis presentations vary in severity, and areassociated with a high morbidity and 1: severity is measured in terms of neurological dam-age (coma, convulsions, status epilepticus, etc.), but also affectsother organs (respiratory/renal/hemodynamic failure, etc.). Therapidity and extent of neurological deterioration within the firstfew hours cannot be RecommendationsGrade B: patients must be hospitalized in a unit familiar withthe management of these types of infections, and if possibleequipped with a continuous monitoring unit (French acronymUSC).Grade B: the following patients must initially be hospitalizedin the ICU/continuous monitoring unit: patients with a Glasgow score (GCS) 13; or patients who experienced more than one seizure, even moreso status epilepticus; or patients requiring intubation to ventilate or protect airways;or patients presenting with respiratory distress syndrome (oftenassociated with aspiration pneumonia); or patients presenting with another organ failure (shock, renalfailure, etc.)

10 ; or patients presenting with behavior disorders incompatible withhospitalization in a standard unit (severely agitated patients,etc.). Anti-infective RationaleLevel 1: following lumbar puncture and when the micro-scopic examination is negative, the potential severity of theencephalitis may require the urgent administration of an empir-ical anti-infective 2: treatment choice must be based on French epidemi-ological and clinical data (anamnesis, travels, contamination,contacts with animals, neurological and extra-neurologicalsigns, etc.) as well as biological data (especially lumbar punctureresults).Level 1: in metropolitan France, HSV, VZV, Mycobacteriumtuberculosis, and Listeria monocytogenes are most frequentlyresponsible for encephalitis in non-HIV-infected adult 2: assessing the benefit/risk ratio of the high dose ofacyclovir (15 mg/kg/8 hours) as an empirical treatment implies:(i) a potentially better efficacy in case of VZV encephalitis; (ii)an excessive risk of toxicity (renal and/or neurological), (iii) atime-limited risk of toxicity ( 48 hours) in case of non-VZVencephalitis; (iv) ratio of the number of individuals exposedto that risk (all suspicions, even minor ones) over the num-ber of true VZV encephalitis patients who might receive thishigh dose regimen.