Cellulite infectieuse chez l’adulte et l’enfant · Ce guide traite du diagnostic et du...

Cellulite infectieuse chez l’adulte et l’enfant Annexes complémentaires du rapport en soutien au guide d’usage optimal

OCTOBRE 2017

GUIDES ET NORMES

Une production de l’Institut national d’excellence en santé et en services sociaux (INESSS)

Cellulite infectieuse chez l’adulte et l’enfant Annexes complémentaires du rapport en soutien au guide d’usage optimal

Le présent document contient les annexes complémentaires au rapport Cellulite infectieuse chez l’adulte et l’enfant.

Le contenu de cette publication a été rédigé et édité par l’INESSS. Ces annexes et le rapport final sont accessibles en ligne dans la section Publications de notre site Web.

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Responsabilité L’Institut rend accessibles les principales informations qui ont servi à la préparation du rapport Cellulite infectieuse chez l’adulte et l’enfant aux lecteurs qui désirent plus de détails sur sa démarche scientifique. Ce document n’a pas fait l’objet d’une révision linguistique. Il ne reflète pas forcément les opinions des autres personnes consultées aux fins du présent dossier.

TABLE DES MATIÈRES

ANNEXE A CRITÈRES ET MODÈLES DE RECHERCHE .................................................................................... 1

ANNEXE B STRATÉGIE DE RECHERCHE D’INFORMATION POUR LES QUESTIONS DE RECHERCHE 1 À 9 .... 2

ANNEXE C SÉLECTION DES DOCUMENTS POUR LES QUESTIONS DE RECHERCHE 1 À 9............................. 5

ANNEXE D LISTE ET CARACTÉRISTIQUES DES ÉTUDES INCLUSES POUR LES QUESTIONS DE RECHERCHE 1 À 9 ...................................................................................................................... 6

ANNEXE E ÉVALUATION DE LA QUALITÉ MÉTHODOLOGIQUE DES GPC ET DES RS .................................. 10

ANNEXE F SOURCE DES PHOTOS PRÉSENTES DANS L’OUTIL D’AIDE AU DIAGNOSTIC (CHEZ L’ADULTE) 15

ANNEXE G SOURCE DES PHOTOS PRÉSENTES DANS L’OUTIL D’AIDE AU DIAGNOSTIC (CHEZ L’ENFANT) 16

ANNEXE H TABLEAUX D’EXTRACTION DES DONNÉES............................................................................... 17

RÉFÉRENCES .............................................................................................................................................. 91

LISTE DES TABLEAUX Tableau A-1 : Modèle de recherche PIPOH – Questions de recherche 1 à 9 ............................................. 1 Tableau B-1 : Mots clés pour la recherche d’information .......................................................................... 2 Tableau E-1 : Critères d’évaluation de la grille AGREE II .......................................................................... 10 Tableau E-2 : Résultats individuels de la qualité des 8 GPC évalués avec la grille AGREE II

(évaluateurs 1 [FSP] et 2 [SG]) .............................................................................................. 11 Tableau E-3 : Qualité globale des GPC selon la grille AGREE II ................................................................. 13 Tableau E-4 : Évaluation de la RS - Grille R-AMSTAR détaillée (évaluateurs 1 [FSP] et 2 [FK]) ................ 14 Tableau H-1 : Extraction des données ...................................................................................................... 17

LISTE DES FIGURES Figure C-1 : Diagramme de flux .................................................................................................................. 5

1

ANNEXE A Critères et modèles de recherche

Tableau A-1 : Modèle de recherche PIPOH – Questions de recherche 1 à 9

PIPOH Description GUO 2016 – Cellulites infectieuses

Population

La population ciblée et les caractéristiques de la maladie, de la condition ou de l’intervention faisant l’objet du GUO.

Population adulte et pédiatrique avec une cellulite infectieuse.

Intervention L’intervention sur laquelle porte le GUO.

L’établissement du diagnostic, l’antibiothérapie, la prévention et le suivi des cas de cellulite infectieuse chez l’adulte et l’enfant

Professionnels/ Personnes

Les professionnels, les intervenants ou les patients ou usagers à qui s’adressera le GUO (utilisateurs du guide).

Les médecins de première ligne (cliniques externes et urgences) ainsi que les pharmaciens et les infirmières.

Objectifs (Outcomes)

Les résultats attendus pour le patient ou l’usager, pour la pratique ou pour la communauté (les objectifs du GUO).

Établir des recommandations quant à la prise en charge et au traitement des cellulites infectieuses chez l’adulte et l’enfant dans le but d’obtenir un usage optimal des antibiotiques.

Healthcare setting and context

Le lieu de l’intervention et le contexte dans lequel le GUO sera implanté.

Dans les cliniques externes, cliniques médicales, cabinets, groupes de médecine familiale, unités de médecine familiale, supercliniques et dans les urgences pour un traitement du patient à domicile ou en centre de jour

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Annexe B Stratégie de recherche d’information pour les questions de recherche 1 à 9

Tableau B-1 : Mots clés pour la recherche d’information

Base de données : PubMed (NLM)

Date de la recherche : 5 décembre 2016 Limites : 2011-2016; anglais et français

#1 exp *cellulitis/ OR exp *erysipelas/

#2 (cellulitis OR erysipelas).ti,ab

#3 (((skin OR soft tissue) ADJ infection*) OR skin structure infection* OR SSTI*).ti,ab

#4 (exp guidelines as topic/ OR exp practice guidelines as topic/ OR guideline.pt OR exp health planning guidelines/ OR practice guideline.pt OR exp consensus/ OR consensus development conference, NIH.pt OR consensus development conference.pt OR exp consensus development conferences, NIH as topic/ OR exp consensus development conferences as topic/ OR exp critical pathways/ OR clinical conference.pt OR exp algorithms/ OR exp review literature as topic/ OR exp meta-analysis as topic/ OR exp meta-analysis/ OR meta-analysis.pt OR exp technology assessment,biomedical/ OR (guideline* OR guide line* OR CPG OR CPGs OR guidance OR practical guide* OR practice parameter* OR (best ADJ3 practice*) OR evidence base* OR consensus OR algorithm* OR (clinical ADJ3 pathway*) OR (critical ADJ3 pathway*) OR recommendation* OR committee opinion* OR policy statement* OR position statement* OR standard OR standards OR (systematic* ADJ3 (review* OR overview* OR literature OR search* OR research*)) OR meta-analy* OR metaanaly* OR met analy* OR metanaly* OR HTA OR HTAs OR technology assessment* OR technology overview* OR technology appraisal*).ti,ab OR (review.pt AND ((medline OR pubmed) AND (cochrane OR embase OR cinahl OR psycinfo)).ti,ab)) NOT (case reports.pt OR comment.pt OR editorial.pt OR letter.pt)

#5 randomized controlled trial.pt OR pragmatic clinical trial.pt OR exp randomized controlled trials as topic/ OR randomized controlled trial/ OR random allocation/ OR double-blind method/ OR single-blind method/ OR placebos/ OR (random* OR sham OR placebo* OR ((singl* OR doubl* OR tripl* OR trebl*) ADJ (blind* OR dumm* OR mask*))).ti,ab

#6 exp cohort studies/ OR cohort*.ti,ab OR controlled clinical trial.pt

#7 (1 OR 2 OR 3) AND (4 OR 5 OR 6)

http://www.ncbi.nlm.nih.gov/pubmed/advanced







3

Base de données : Embase (OvidSP)


#1 exp *cellulitis/ OR exp *erysipelas/

#2 (cellulitis OR erysipelas).ti,ab


#4 (exp practice guideline/ OR health care planning/ OR consensus/ OR algorithm/ OR systematic review/ OR "systematic review (topic)"/ OR meta-analysis/ OR "meta analysis (topic)"/ OR biomedical technology assessment/ OR (guideline* OR guide line* OR CPG OR CPGs OR guidance OR practical guide* OR practice parameter* OR (best ADJ3 practice*) OR evidence base* OR consensus OR algorithm* OR (clinical ADJ3 pathway*) OR (critical ADJ3 pathway*) OR recommendation* OR committee opinion* OR policy statement* OR position statement* OR standard OR standards OR (systematic* ADJ3 (review* OR overview* OR literature OR search* OR research*)) OR meta-analy* OR metaanaly* OR met analy* OR metanaly* OR HTA OR HTAs OR technology assessment* OR technology overview* OR technology appraisal*).ti,ab.) NOT (case report/ OR editorial/ OR letter/)

#5 randomized controlled trial/ OR "randomized controlled trial (topic)"/ OR randomization/ OR double blind procedure/ OR single blind procedure/ OR placebo/ OR (random* OR sham OR placebo* OR ((singl* OR doubl* OR tripl* OR trebl*) ADJ (blind* OR dumm* OR mask*))).ti,ab

#6 exp cohort analysis/ OR exp longitudinal study/ OR exp prospective study/ OR exp follow up/ OR cohort*.ti,ab

#7 (1 OR 2 OR 3) AND (4 OR 5 OR 6)

Base de données : EBM Reviews (OvidSP)


#1 (cellulitis OR erysipelas).ti,ab,hw,kw


#3 1 OR 2

Autres sources Les autres sources consultées sont les suivantes :

• Guidelines International Network (G-I-N)

• National Guideline Clearinghouse (NGC)

• Haute Autorité de Santé (HAS)

• National Institute for Health and Care Excellence (NICE) « Evidence search »

• American Academy of Otorhinolaryngology – Head and Neck Surgery

• Société Française d'ORL et de Chirurgie de la Face et du Cou

• Société canadienne d’otolaryngologie et de chirurgie cervico-faciale

• American Academy of Dermatology

• Association canadienne de dermatologie

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• British Association of Dermatology (BAD)

• European Dermatology Forum

• Société Française de Dermatologie

• Canadian Ophthalmological Society

• American Academy of Ophthalmology

• Association dentaire canadienne

• American Dental Association

• Scottish Dental Clinical Effectiveness Programme

Les monographies canadiennes des différents antibiotiques ont été consultées, de même qu’une recherche de la littérature grise a été effectuée afin d’identifier des documents contenant des informations sur les taux de résistances des différents pathogènes impliqués dans les cellulites infectieuses au Québec et au Canada. Les sites Web des agences et organismes suivants ont été visités :

• Système canadien de surveillance de la résistance aux antimicrobiens

• Institut national de santé publique du Québec/Laboratoire de santé publique du Québec (INSPQ/LSPQ)

5

ANNEXE C Sélection des documents pour les questions de recherche 1 à 9

Figure C-1 : Diagramme de flux

Documents repérés dans les bases de données

(n = 2214)

Documents repérés dans d’autres sources

(n = 25)

Documents repérés (n = 2239)

Documents sélectionnés (n = 63)

Documents exclus :

• Type de document autre que GPC : n = 43

• Hors-sujet : n = 7 • Document inaccessible :

n = 4 • Faible qualité et non

canadien : n = 3

Documents inclus dans la synthèse qualitative

(n = 6)

Repé

rage

Sé

lect

ion

Incl

usio

n

Documents exclus :

Doublon : n = 4 Après lecture des titres

et résumés : n = 2172

6

ANNEXE D Liste et caractéristiques des études incluses pour les questions de recherche 1 à 9

Type Guide de pratique clinique

Organisme Infectious Diseases Society of America (IDSA)

Auteurs Dennis L. Stevens, Alan L. Bisno, Henry F. Chambers, E. Patchen Dellinger, Ellie J. C. Goldstein, Sherwood L. Gorbach, Jan V. Hirschmann, Sheldon L. Kaplan, Jose G. Montoya, James C. Wade.

Pays États-Unis

Titre Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America

Année 2014

Objectif

Ce guide traite du diagnostic et du traitement approprié de diverses infections de la peau et des tissus mous, allant des infections superficielles mineures aux infections potentiellement léthales telles que la fasciite nécrosante. (mise à jour)

Période de la recherche documentaire Aucune restriction de date

Sources d’information Banques de données Library of Congress, LISTA (EBSCO) et PubMed.

Conflit d’intérêts

D. L. S. a aucun conflit d’intérêt actuellement et reçoit présentement du soutien à la recherche du « Department of Veterans Affairs » et des « National Institutes of Health ». A. L. B. a reçu des honoraires de UpToDate. H. F. C. a agit à titre de consultant pour Pfizer, AstraZeneca, Theravance et Trius, et a reçu des actions/obligations de Merck et Trius. E. P. D. a agit à titre de consultant; a reçu des subventions de recherche clinique et/ou des honoraires de conférence de Bayer, Merck, Wyeth-Ayerst, AstraZeneca, Pfizer, Ortho-McNeil, Cubist, Vicuron, InterMune, Peninsula, Johnson & Johnson, Cepheid, Replidyne, Kimberley-Clark, Targanta, Schering-Plough, Enturia, Optimer Pharmaceuticals, Cadence, Implicit, Cardinal, Durata, 3M, Applied Medical et BD-GeneOhm; et a reçu une subvention pour un essai clinique de Tetraphase. E. J. C. G. a agit à titre de consultant pour Schering-Plough, ViraPharm, Replidyne, Occulus Innovative Sciences, Theravance, Cerexa, Merck et Optimer Pharmaceuticals; a reçu des honoraires de Merck, Johnson & Johnson; et a reçu des subventions de recherche de Replidyne, Occulus Innovative Sciences, Cubist, Theravance, Pfizer, Cerexa, Johnson & Johnson, Merck et Optimer Pharmaceuticals. S. L. G. a reçu des actions/obligations d’Optimer Pharmaceuticals, Cubist Pharmaceuticals et Cempra Pharmaceuticals; a reçu des honoraires de l’IDSA (Éditeur, Clinical Infectious Diseases); a agit à titre de consultant

7

pour Cempra Pharmaceuticals; a reçu des subventions des « National Institutes of Health ». S. L. K. a agit à titre de consultant pour Novartis, Pfizer et Wyeth; a été chercheur principal pour Cubist, Cerexa et Optimer; et a reçu des honoraires de UpToDate et Merck. Tous les autres auteurs n’ont rapporté aucun conflit d’intérêts potentiel.


Organisme Infectious Diseases Society of America (IDSA)

Auteurs

Catherine Liu, Arnold Bayer, Sara E. Cosgrove, Robert S. Daum, Scott K. Fridkin, Rachel J. Gorwitz, Sheldon L. Kaplan, Adolf W. Karchmer, Donald P. Levine, Barbara E. Murray, Michael J. Rybak, David A. Talan, Henry F. Chambers.

Pays États-Unis

Titre Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children

Année 2011

Objectif Ce guide traite du diagnostic et du traitement approprié des infections causées par les souches de Staphylococcus aureus résistantes à la méthicilline.

Période de la recherche documentaire 1961 à 2010

Sources d’information Banque de données PubMed.

Conflit d’intérêts

H.F.C. a reçu des honoraires et des subventions de recherche et a agi à titre de consultant pour Cubist, Ortho-McNeil, Pfizer, Theravance, and Targanta. S. E. C. a reçu des honoraires de Forest et RibX, a agi à titre de consultant pour Merck et a reçu un soutien à la recherche d’Astellas, Cubist et AdvanDx. R.D. a reçu des subventions de recherché de Pfizer, Clorox, Sanofi Pasteur, Sage, and GeneOhm. S.L.K. a reçu des subventions de recherché de Pfizer, a agi à titre de conseiller en leadership SARM pour Pfizer, et participe dans une étude pédiatrique dur la daptomycine. A.W.K. a reçu des honoraires et des subventions de Cubist Pharmaceuticals, Merck, Wyeth et Pfizer et a agi à titre de consultant pour Cubist Pharmaceuticals, Theravance, Astellas, Pfizer, Merck et Ortho-McNeil et a posséder des actions de Cubist Pharmaceutical, Pfizer et Johnson and Johnson. D.P.L. a reçu un soutien à la recherche de Cubist, Johnson & Johnson et Theravance et a agi à titre de conférencier pour Cubist. B.E.M. a agi à titre de consultant et a reçu du soutien à la recherche de Johnson & Johnson, Astellas, Pfizer, Cubist, Theravance, Targanta, Sanofi-

8

Aventis, Vicuron Pharmaceuticals et Wyeth-Ayerst. M.R. a reçu des subventions et/ou a agi à titre de conférencier consultant pour Pfizer, Cubist, Theravance/Astellas, Targanta et Johnson & Johnson. D.A.T. a siégé sur le conseil consultatif de Pfizer, Ortho-McNeil, Astellas, Schering-Plough et Replidyne. Tous les autres auteurs n’ont rapporté aucun conflit d’intérêts potentiel.


Organisme Seattle Children’s Hospital

Auteurs Lauren Wilson et Derya Caglar.

Pays États-Unis

Titre Cellulitis and abscess

Année 2013

Objectif Ce guide traite du diagnostic et du traitement approprié des infections de la peau de type cellulite ou abcès chez les enfants.

Période de la recherche documentaire 2004-novembre 2012

Sources d’information Banque de données MEDLINE, Cochrane Database of Systematic Reviews, Embase, Clinical Evidence, National Guideline Clearinghouse et TRIP.

Conflit d’intérêts Non-rapporté


Organisme Ne s’applique pas

Auteurs Denise Nassisi et Marisa L. Oishi.

Pays États-Unis

Titre Evidence-based guidelines for evaluation and antimicrobial therapy for common emergency department infections

Année 2012

Objectif Ce guide traite de l’évaluation et du traitement antibiotique approprié des infections communément rencontrées à l’urgence (incluant la cellulite infectieuse).

Période de la recherche documentaire Non-rapporté

Sources d’information Banque de données PubMed, Ovid MEDLINE®, Cochrane Database of Systematic Reviews, Agency for Healthcare Research and Quality, National Guideline Clearinghouse.

Conflit d’intérêts Les auteurs n’ont rapporté aucun conflit d’intérêts significatif.

9


Organisme Ne s’applique pas

Auteurs The Provincial Antibiotic Advisory Team, Health PEI.

Pays Canada

Titre Provincial Antibiotic Advisory Team skin and soft tissue infection empiric treatment guidelines

Année 2014

Objectif Ce guide décrit les différents traitements antibiotiques recommandés pour le traitement des cellulites infectieuses et des érysipèles.

Période de la recherche documentaire Non-rapporté

Sources d’information Non-rapporté

Conflit d’intérêts Non-rapporté

Type : Revue systématique

Organisme : Ne s’applique pas Auteurs : Thomas R. Flynn

Pays : États-Unis Titre : What are the antibiotics of choice for odontogenic infections, and how

long should the treatment course last? Année : 2011

Objectifs : Évaluer quels sont les meilleurs choix d’antibiothérapie empirique pour le traitement des infections odontogènes et quelle est la durée de traitement optimale pour ce type d’infections.

Période de la recherche documentaire :

Essais cliniques : de la création de la base de donnée jusqu’au 27 décembre 2010. Études en laboratoire : du 1er janvier 2000 au 27 décembre 2010.

Sources d’information : PubMed, DARE (Database of Abstracts of Reviews of Effects) et le « Controlled Trials Register » de la « Cochrane Library »

Conflits d’intérêts : L’auteur n’a rapporté aucun conflit d’intérêts potentiel.

10

ANNEXE E Évaluation de la qualité méthodologique des GPC et des RS

Tableau E-1 : Critères d’évaluation de la grille AGREE II

Domaine 1. Champ et objectifs (score 1 à 7) 1. Le ou les objectifs de la RPC sont décrits explicitement.

2. La ou les questions de santé couvertes par la RPC sont décrites explicitement.

3. La population à laquelle la RPC doit s'appliquer est décrite explicitement.

Domaine 2. Participation des groupes concernés (score 1 à 7) 4. Le groupe de travail ayant élaboré la RPC inclut des représentants de tous les groupes professionnels concernés. 5. Les opinions et leurs préférences de la population cible ont été identifiées.

6. Les utilisateurs cibles de la RPC sont clairement définis.

Domaine 3. Rigueur d’élaboration de la RPC (score 1 à 7) 7. Des méthodes systématiques ont été utilisées pour rechercher les preuves scientifiques. 8. Les critères de sélection des preuves sont clairement décrits. 9. Les forces et les limites des preuves scientifiques sont clairement définies. 10. Les méthodes utilisées pour formuler les recommandations sont clairement décrites. 11. Les bénéfices, les effets secondaires et les risques en termes de santé ont été pris en considération dans la formulation des recommandations. 12. Il y a un lien explicite entre les recommandations et les preuves scientifiques sur lesquelles elles reposent. 13. La RPC a été revue par des experts externes avant sa publication. 14. Une procédure d'actualisation de la RPC est décrite. Domaine 4. Clarté et présentation (score 1 à 7) 15. Les recommandations sont précises et sans ambiguïté. 16. Les différentes options de prise en charge de l'état ou du problème de santé sont clairement présentées. 17. Les recommandations clés sont facilement identifiables. Domaine 5. Applicabilité (score 1 à 7) 18. La RPC décrit les éléments facilitant son application et les obstacles 19. La RPC offre des conseils et/ou des outils sur les façons de mettre les recommandations en pratique. 20. Les répercussions potentielles sur les ressources de l'application des recommandations ont été examinées. 21. La RPC propose des critères de suivi et de vérification. Domaine 6. Indépendance éditoriale (score 1 à 7) 22. Le point de vue des organismes de financement n'a pas influencé le contenu de la RPC. 23. Les intérêts divergents des membres du groupe ayant élaboré la RPC ont été pris en charge et documentés. Appréciation générale de la qualité du guide (score de 1 à 7)

Recommandation de l'utilisation du guide (oui ou non)

11

Tableau E-2 : Résultats individuels de la qualité des 8 GPC évalués avec la grille AGREE II

(évaluateurs 1 [FSP] et 2 [SG])

IDSA, 2014 [Stevens et al., 2014]

IDSA, 2011 [Liu et al.,

2011]

Seattle, 2013

[Wilson et Caglar, 2013]

[Nassisi et Oishi, 2012]

[Esposito et al., 2011]

[Atfeh et Khalil, 2015]

[Sartelli et al., 2014]

Évaluateurs 1 2 1 2 1 2 1 2 1 2 1 2 1 2 Domaines de la grille AGREE II Domaine 1. Champ et objectifs 1. Le ou les objectifs de la RPC sont décrits explicitement. 5 7 7 7 7 7 7 7 6 3 6 4 1 1

2. La ou les questions de santé couvertes par la RPC sont décrites explicitement. 7 7 7 7 5 7 7 7 6 2 5 1 2 2

3. La population à laquelle la RPC doit s'appliquer est décrite explicitement. 7 7 7 7 7 7 5 5 6 4 5 1 4 4

Domaine 2. Participation des groupes concernés 4. Le groupe de travail qui a élaboré la RPC inclut des représentants de tous les groupes professionnels concernés.

5 6 5 5 4 6 5 5 4 5 6 6 6 6

5. Les opinions et les préférences de la population cible ont été précisées. 1 1 1 1 1 1 1 1 1 1 1 1 1 1

6. Les utilisateurs cibles de la RPC sont clairement définis. 7 7 6 7 5 6 7 7 1 1 1 1 1 1

Domaine 3. Rigueur d’élaboration de la RPC 7. Des méthodes systématiques ont été appliquées pour rechercher les preuves scientifiques.

5 5 5 7 5 7 2 2 3 2 6 7 1 1

8. Les critères de sélection des preuves sont clairement décrits. 5 1 7 7 7 7 1 1 1 1 7 4 1 1 9. Les forces et les limites des preuves scientifiques sont clairement définies. 6 7 7 7 4 7 6 6 7 6 1 1 3 2 10. Les méthodes appliquées pour formuler les recommandations sont clairement décrites.

3 5 4 5 1 2 3 3 4 4 1 4 3 3

11. Les bénéfices, les effets secondaires et les risques en termes de santé ont été pris en considération dans la formulation des recommandations.

5 5 7 7 3 3 5 5 3 5 1 1 4 4

12. Il y a un lien explicite entre les recommandations et les preuves scientifiques sur lesquelles elles reposent.

5 7 7 7 6 1 5 6 7 7 1 1 5 7

13. La RPC a été revue par des experts externes avant sa publication. 3 5 4 4 2 1 2 1 4 1 4 2 1 1 14. Une procédure d'actualisation de la RPC est décrite. 5 5 6 4 6 7 1 1 1 1 1 1 1 1

Domaine 4. Clarté et présentation 15. Les recommandations sont précises et sans ambiguïté. 6 7 6 7 6 7 6 7 6 5 5 5 7 7

16. Les différentes options de prise en charge de l'état ou du problème de santé sont clairement présentées.

7 7 7 7 7 7 7 7 7 7 7 7 5 7

17. Les recommandations clés sont facilement repérables. 7 7 7 7 7 7 7 7 7 4 6 4 7 5

Domaine 5. Applicabilité 18. La RPC décrit les éléments facilitant son application ainsi que les obstacles. 1 1 1 7 1 1 1 1 1 1 1 1 1 1

19. La RPC offre des conseils ou des outils sur les façons de mettre les 1 1 2 1 6 5 1 1 1 1 1 1 1 1

12


IDSA, 2011 [Liu et al.,

2011]

Seattle, 2013

[Wilson et Caglar, 2013]

[Nassisi et Oishi, 2012]

[Esposito et al., 2011]

[Atfeh et Khalil, 2015]

[Sartelli et al., 2014]

Évaluateurs 1 2 1 2 1 2 1 2 1 2 1 2 1 2 recommandations en pratique. 20. Les répercussions potentielles sur les ressources de l'application des recommandations ont été examinées.

1 1 1 1 1 1 1 1 1 1 1 1 1 1

21. La RPC propose des critères de suivi et de vérification. 1 1 1 1 7 5 1 1 1 1 1 1 1 1

Domaine 6. Indépendance éditoriale 22. Le point de vue des organismes de financement n'a pas influé sur le contenu de la RPC.

4 4 4 4 1 1 7 7 1 1 1 1 1 1

23. Les intérêts divergents des membres du groupe qui a élaboré la RPC ont été pris en charge et documentés.

7 7 7 7 1 1 5 6 1 1 3 3 3 6

Somme de la cotation pour les 23 critères 104 111 116 124 100 104 93 95 80 65 72 59 61 65

Qualité générale du guide (1 à 7) 5 5 5 5 4 5 4 4 3 2 3 2 3 4 Recommandation de l'utilisation du guide Oui Oui Oui Oui Oui Oui Oui Oui Non Non Non Non Non Non

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Tableau E-3 : Qualité globale des GPC selon la grille AGREE II


IDSA, 2011 [Liu et al., 2011]

Seattle, 2013 [Wilson et Caglar, 2013] [Nassisi et Oishi, 2012]

Évaluateurs 1 2 1 2 1 2 1 2

Dimensions T* %† T* %† T* %† T* %†

Champ d’application et objectifs 19 21 40 94,4 21 21 42 100 19 21 40 94,4 19 19 38 88,9

Participation des groupes concernés 13 14 27 58,3 12 13 25 52,8 10 13 23 47,2 13 13 26 55,6

Rigueur du proc. d’élaboration du guide 37 40 77 63,5 47 48 95 82,3 34 35 69 55,2 25 25 50 35.4

Clarté et présentation 20 21 41 97,2 20 21 41 97,2 20 21 41 97,2 20 21 41 97,2

Applicabilité 4 4 8 0,0 5 10 15 14,6 15 12 27 39,6 4 4 8 0,0

Indépendance éditoriale 11 11 22 75,0 11 11 22 75,0 2 2 4 8,3 12 13 25 87,5

Total 104 111 215 116 124 240 100 104 204 93 95 188

Score global 61,2 70,3 57,2 51,4

Recommandation - utilisation guide Oui Oui Oui Oui

[Esposito et al., 2011] [Atfeh et Khalil, 2015] [Sartelli et al., 2014]

Évaluateurs 1 2 1 2 1 2

Dimensions T* %† T* %† T* %†

Champ d’application et objectifs 18 9 36 83,3 16 6 22 44,4 7 7 14 22,2

Participation des groupes concernés 6 7 13 19,4 8 8 16 27,8 8 8 16 27,8

Rigueur du proc. d’élaboration du guide 30 27 57 42,7 22 21 43 28,1 19 20 39 24,0

Clarté et présentation 20 16 36 83,3 18 16 34 77,8 19 19 38 88,9

Applicabilité 4 4 8 0,0 4 4 8 0,0 4 4 8 0,0

Indépendance éditoriale 2 2 4 0,0 4 4 8 16,7 4 7 11 29,2

Total 80 65 145 72 59 131 61 65 126

Score global 35,9 30,8 29,0

Recommandation - utilisation guide Non Non Non

*Somme des scores obtenus par domaine pour chaque évaluateur. † Pourcentage des scores par domaine = [(Total – score minimal possible (46))/ (score maximal possible (322) -score minimal possible(46))] x 100. ** Score global = [(Total des scores pour l’ensemble des domaines – score minimal possible (46))/ (score maximal possible (322) - score minimal

possible(46))] x 100.

14

Tableau E-4 : Évaluation de la RS - Grille R-AMSTAR détaillée (évaluateurs 1 [FSP] et 2 [FK])

[FLYNN, 2011]

Évaluateurs 1 2

1. Un plan de recherche établi a priori est-il fourni? 3 3 2. La sélection des études et l’extraction des données ont-ils été confiés à au moins deux personnes? 1 1

3. La recherche documentaire était-elle exhaustive? 3 4 4. La nature de la publication (littérature grise, par exemple) était-elle un critère d’inclusion? 2 2

5. Une liste des études (incluses et exclues) est-elle fournie? 4 4 6. Les caractéristiques des études incluses sont-elles indiquées? 1 2

7. La qualité scientifique des études incluses a-t-elle été évaluée et consignée? 2 2

8. La qualité scientifique des études incluses dans la revue a-t-elle été utilisée adéquatement dans la formulation des conclusions?

3 4

9. Les méthodes utilisées pour combiner les résultats des études sont-elles appropriées? 1 1

10. La probabilité d’un biais de publication a-t-elle été évaluée? 1 2

11. Les conflits d’intérêts ont-ils été déclarés? 2 2

Total 23 27

Pourcentage moyen 56,8 %

Qualité méthodologique Moyenne

15

Annexe F Source des photos présentes dans l’outil d’aide au diagnostic (chez l’adulte)

Cellulite infectieuse et signaux d’alarmes :

Les photos #1, 2 et 5 sont utilisées avec l’autorisation du Dre Georgette Leclerc, Département de médecine spécialisée, Service de dermatologie, Centre de santé et de services sociaux de Chicoutimi.

La photo #3 est utilisée avec l’autorisation du Dr Julien Ghannoum, Service de médecine dentaire, Hôpital Notre-Dame du Centre Hospitalier Universitaire de Montréal.

La photo #4 est utilisée avec l’autorisation du Dr Stan L. Block et provient de : Block SL, Getting an eyeful of preseptal cellulitis. Pediatr Ann 2013;42(3):99-102.

La photo #6 est utilisée avec l’autorisation du Dr Marc Lebel, Service des maladies infectieuses, Centre Hospitalier Universitaire Sainte-Justine de Montréal.

La photo #7 a été reproduite avec l'autorisation de John N. Harrington, MD, FACS, Baylor University Medical Center, publiée par Medscape Drugs & Diseases (http://emedicine.medscape.com), 2017. Disponible à : http://emedicine.medscape.com/article/1217858-overview.

Diagnostic différentiel :

Les photos #1, 6 et 9 sont utilisées avec l’autorisation du Dre Georgette Leclerc, Département de médecine spécialisée, Service de dermatologie, Centre de santé et de services sociaux de Chicoutimi.

Les photos #2, 5, 7 et 8 sont utilisées avec l’autorisation de shutterstock.com.

Les photos #3 et 11 sont utilisées avec l’autorisation du Dr Afshin Hatami, Département de dermatologie, Centre Hospitalier Universitaire Sainte-Justine de Montréal.

La photo #4 provient de : Primary Care Dermatology Society (PCDS). Figure 3 Gravitational eczema - Both legs affected. Dans : Eczema: Gravitational eczema (syn. varicose eczema or stasis dermatitis) [site Web]. 2016. Disponible à : http://www.pcds.org.uk/clinical-guidance/eczema-gravitational-eczema-syn.-varicose-eczema-or-stasis-dermatitis.

La photo #10 provient de : Primary Care Dermatology Society (PCDS). Figure 6 Erythema migrans. Dans : Lyme disease (and erythema migrans) [site Web]. 2017. Disponible à : http://www.pcds.org.uk/clinical-guidance/lyme-disease#images.

http://emedicine.medscape.com/

http://emedicine.medscape.com/article/1217858-overview

http://www.pcds.org.uk/clinical-guidance/eczema-gravitational-eczema-syn.-varicose-eczema-or-stasis-dermatitis

http://www.pcds.org.uk/clinical-guidance/eczema-gravitational-eczema-syn.-varicose-eczema-or-stasis-dermatitis

http://www.pcds.org.uk/clinical-guidance/lyme-disease


16

Annexe G Source des photos présentes dans l’outil d’aide au diagnostic (chez l’enfant)

Cellulite infectieuse et signaux d’alarmes :

Les photos #1 et 2 sont utilisées avec l’autorisation du Dre Georgette Leclerc, Département de médecine spécialisée, Service de dermatologie, Centre de santé et de services sociaux de Chicoutimi.

La photo #3 est utilisée avec l’autorisation du Dr Julien Ghannoum, Service de médecine dentaire, Hôpital Notre-Dame du Centre Hospitalier Universitaire de Montréal.

La photo #4 est utilisée avec l’autorisation du Dr Stan L. Block et provient de : Block SL, Getting an eyeful of preseptal cellulitis. Pediatr Ann 2013;42(3):99-102.

La photo #5 est utilisée avec l’autorisation du Dr Marc Lebel, Service des maladies infectieuses, Centre Hospitalier Universitaire Sainte-Justine de Montréal.

La photo #6 a été reproduite avec l'autorisation de John N. Harrington, MD, FACS, Baylor University Medical Center, publiée par Medscape Drugs & Diseases (http://emedicine.medscape.com/), 2017. Disponible à: http://emedicine.medscape.com/article/1217858-overview.

Diagnostic différentiel :

Les photos #1 et 7 sont utilisées avec l’autorisation du Dre Georgette Leclerc, Département de médecine spécialisée, Service de dermatologie, Centre de santé et de services sociaux de Chicoutimi.

Les photos #2, 4 et 5 sont utilisées avec l’autorisation de shutterstock.com.

Les photos #3, 6 et 9 sont utilisées avec l’autorisation du Dr Afshin Hatami, Département de dermatologie, Centre Hospitalier Universitaire Sainte-Justine de Montréal.

La photo #8 provient de : Primary Care Dermatology Society (PCDS). Figure 6 Erythema migrans. Dans : Lyme disease (and erythema migrans) [site Web]. 2017. Disponible à : http://www.pcds.org.uk/clinical-guidance/lyme-disease#images.

http://emedicine.medscape.com/






17

ANNEXE H Tableaux d’extraction des données

Tableau H-1 : Extraction des données

Stevens 2014 (Infectious Diseases Society of America)

États-Unis Qualité modérée (score

61)

Liu 2011 (Infectious

Diseases Society of America) États-Unis

Qualité modérée (score 70)

Wilson 2013 (Seattle Children’s

Hospital) États-Unis


Nassisi 2012

États-Unis Qualité modérée

(score 51)

HPEI 2014 (Health Prince

Edward Island) Canada

(N/A)

GPCs utilisés pour le GUO sur la

rhinosinusite Données contextuelles

Populations cibles Otherwise healthy hosts and compromised hosts of all age groups.

Methicillin- Resistant Staphylococcus aureus Infections in Adults and Children.

Suspected skin/soft tissue infection in children > 44 weeks CGA.

Management of common infectious diseases presenting to the ED.

Non-spécifié Chow 2012: Children and Adults Desrosiers 2011: Limited to the adult population Rosenfeld 2015: Adults Skye 2013: Non-immune compromised adults Wald 2013: Children Aged 1 to 18 Years

∅

Généralités Pathogènes

Combined data from specimen cultures, serologic studies [41, 48–51], and other methods (eg, immunohistochemical staining to detect antigens in skin

In the pre–CA MRSA era, microbiologic investigations using needle aspiration or punch biopsy cultures of nonpurulent cellulitis

Nonpurulent cellulitis is usually due to group A streptococci (although studies are limited due to the difficulty culturing from these infections)

∅ Pathogens in typical cellulitis can include β-hemolytic Streptococcus (Group A, B, C, and G) with Group B more common with diabetics, PVD, recurrent infections,

Rhinosinusites bactériennes (pouvant se compliquer en cellulite périorbitaire/orbitaire: Chow 2012, Desrosiers

Dumaresq 2016, CISSS Chaudière-Appalaches : Les streptocoques bêta-hémolytiques (groupes A, B, C et G) sont les

18



61)







Nassisi 2012


(score 51)



(N/A)



biopsies [51, 52]), suggests that the vast majority of these infections arise from streptococci, often group A, but also from other groups, such as B, C, F, or G. Staphylococcus aureus less frequently causes cellulitis, but cases due to this organism are typically associated with an open wound or previous penetrating trauma, including sites of illicit drug injection. MRSA is an unusual cause of typical cellulitis. A prospective study of patients with cellulitis in a medical center with a high incidence of other MRSA-related SSTIs demonstrated that treatment with β-lactams, such as cefazolin or oxacillin, was successful in 96% of patients, suggesting that cellulitis due to MRSA is uncommon

identified b-hemolytic streptococci and S. aureus as the main pathogens. In the majority of cases, a bacterial etiology was not identified, but MSSA was the most common pathogen among those who were culture positive [128–133]. A retrospective case-control study in children with nonpurulent cellulitis found that, compared with b-lactams, clindamycin provided no additional benefit, whereas TMP-SMX was associated with a slightly higher failure rate [134]. The only prospective study of nonculturable cellulitis among hospitalized inpatients found that b-hemolytic streptococci (diagnosed by acute- and

Purulent cellulitis may be caused by MSSA, MRSA, or group A streptococci (GAS). • Approximately 27% of S. aureus isolates from wounds are MRSA at Seattle Children’s (2012-13 data)

trauma/excoriation, and lymphedema. Staphylococcus aureus in non-immunocompromised patients typically presents with folliculitis or trauma leading to an abscess. Community acquired MRSA can occasionally present as streptococcal disease above. Outside of water exposure, bites, burns, or trauma (including through footwear), Gram-negatives do not have a significant role in an immunocompetent host.

2011, Rosenfeld 2015, Skye 2013, Wald 2013: Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Autres pathogènes Chow 2012, Desrosiers 2011, Skye 2013 : Streptococcus pyogenes (or other streptococcus), oral anaerobes Autres pathogènes Chow 2012, Desrosiers 2011 : gram-negative bacilli

principaux agents étiologiques des cellulites /érysipèles. Tétrault 2016, INSPQ/LSPQ : La proportion de souches de SARM parmi le nombre total de Staphylococcus aureus isolés de pus superficiels et pus profonds de la peau et des tissus mous de patients provenant de la communauté est de 10 %. Ce taux varie de 4 à 15 % selon les régions, en excluant les régions «Nunavik, Baie James»

19



61)







Nassisi 2012


(score 51)



(N/A)



and treatment for that organism is usually unnecessary [50] In nonpurulent cellulitis, the clinical isolation rate of a pathogen is <20%. This leaves the modern clinician with an unconfirmed diagnosis 80% of the time. Several other organisms can cause cellulitis, but usually only in special circumstances, such as animal bites, freshwater or saltwater immersion injuries, neutropenia, or severe cell-mediated immunodeficiency. (Animal bites) Purulent bite wounds and abscess are more likely to be polymicrobial (mixed aerobes and anaerobes), whereas nonpurulent wounds commonly yield staphylococci and streptococci [156, 157]. Pasteurella species are commonly isolated from both nonpurulent

convalescent-phase serological testing for anti-streptolysin-O and anti-DNase-B antibodies or positive blood culture results) accounted for 73% of the cases; despite the lack of an identifiable etiology in 27% of cases, the overall clinical response rate to b-lactam therapy was 96% [135]. Although additional research is needed to characterize the microbiology of nonpurulent cellulitis, currently available data suggests that b-hemolytic streptococci may be the primary pathogen. Among patients presenting with purulent SSTI to 11 emergency departments throughout the United States, CA-MRSA was the

20



61)







Nassisi 2012


(score 51)



(N/A)



wounds with or without lymphangitis and from abscesses. Additionally, nonpurulent wound infections may also be polymicrobial [156]. Human bites may occur from accidental injuries, purposeful biting, or closed-fist injuries. The bacteriologic characteristics of these wounds are complex, but include aerobic bacteria, such as Streptococci, S. aureus, and Eikenella corrodens, as well as with multiple anaerobic organisms, including Fusobacterium, Peptostreptococcus, Prevotella, and Porphyromonas species. Compléments d’information tirés du GPC IDSA 2005: Many other infectious agents can produce cellulitis, but usually only in special circumstances. With cat or dog bites, for

dominant organism, isolated from 59% of patients, followed by MSSA (17%); b- hemolytic streptococci accounted for a much small proportion (2.6%) of these infections [11].

21



61)







Nassisi 2012


(score 51)



(N/A)



example, the organism responsible is typically Pasteurella species, especially P. multocida, or Capnocytophaga canimorsus. A. hydrophila may cause cellulitis following immersion in fresh water, whereas infection after saltwater exposure can arise from Vibrio species, particularly V. vulnificus in warm climates. Periorbital cellulitis due to Haemophilus influenza can occur in children. Diagnostic and therapeutic considerations of this infection have been reported by the Committee on Infectious Diseases, American Academy of Pediatrics [6]. In neutropenic hosts, infection may be due to Pseudomonas aeruginosa or other gram-negative bacilli, and in patients infected with HIV, the responsible organism may be Helicobacter cinaedi [71].

22



61)







Nassisi 2012


(score 51)



(N/A)



Occasionally, Cryptococcus neoformans causes cellulitis in patients with deficient cell-mediated immunity. The predominant pathogens in bite wounds are the normal oral flora of the biting animal, along with human skin organisms and occasional secondary invaders (e.g., S. aureus and S. pyogenes). The average wound yields 5 types of bacterial isolates (range, 0–16 types of bacterial isolates), with ∼60% yielding mixed aerobic and anaerobic bacteria. Pasteurella species are isolated from 50% of dog bite wounds and 75% of cat bite wounds. Staphylococci and streptococci are found in ∼40% of bites from both types of animals. Facultative gram-negative rods are uncommon. Bacteroides species,

23



61)







Nassisi 2012


(score 51)



(N/A)



fusobacteria, Porphyromonas species, Prevotella heparinolytica, proprionibacteria, and peptostreptococci are common anaerobes isolated from both dog bite wounds and cat bite wounds [113]. The bacteriologic characteristics of these [human bite] wounds reflect the normal oral flora of the biter, with streptococci (especially viridans streptococci) in 80% of wounds, as well as staphylococci, Haemophilus species, and Eikenella corrodens as prominent aerobic pathogens [112, 115].

Définition “Cellulitis” and “erysipelas” refer to diffuse, superficial, spreading skin infections. The term “cellulitis” is not appropriate for cutaneous inflammation associated with collections of pus, such as in septic bursitis,

∅ Cellulitis is an infection of the skin and underlying soft tissue. It is characterized by pain, erythema, edema and warmth. - Purulent cellulitis is cellulitis associated with drainage or

∅ ∅ ∅ ∅

24



61)







Nassisi 2012


(score 51)



(N/A)



furuncles, or skin abscesses. For example, when cutaneous redness, warmth, tenderness, and edema encircle a suppurative focus such as an infected bursa, the appropriate terminology is “septic bursitis with surrounding inflammation,” rather than “septic bursitis with surrounding cellulitis.” This distinction is clinically crucial, for the primary treatment of cellulitis is antimicrobial therapy, whereas for purulent collections the major component of management is drainage of the pus, with antimicrobial therapy either being unnecessary or having a subsidiary role (Figure 1 and Table 2).

exudate, currently or by history. A drainable abscess may or may not be present. - Nonpurulent cellulitis has no drainage, exudate or abscess present.

Autres These infections arise when microbes breach the cutaneous surface, especially in patients with fragile skin or diminished

∅ ∅ ∅ ∅ Desrosiers 2011: Periorbital or orbital cellulitis is the most common complication of Acute Bacterial RhinoSinusitis and

∅

25



61)







Nassisi 2012


(score 51)



(N/A)



local host defenses from such conditions as obesity, previous cutaneous trauma (including surgery), prior episodes of cellulitis, and edema from venous insufficiency or lymphedema [36, 37]. The origin of the disrupted skin surface may be obvious, such as trauma, ulceration, and preexisting cutaneous inflammation, but often the breaks in the skin are small and clinically unapparent. These infections are most common on the lower legs. Compléments d’information tirés du GPC IDSA 2005: The origin of the disrupted cutaneous barrier may be trauma, preexisting skin infections such as impetigo or ecthyma, ulceration, fissured toe webs from maceration

most often caused by acute ethmoid and/or frontal disease [36,37]. Infection spreads from the sinuses to the orbit with relative ease [38,39].

26



61)







Nassisi 2012


(score 51)



(N/A)



or fungal infection, and inflammatory dermatoses, such as eczema.

Prévention Facteurs de risque et mesures préventives

Patients with a previous attack of cellulitis, especially involving the legs, have annual recurrences rates of about 8%–20% [65–67]. Edema, especially lymphedema and other local risk factors such as venous insufficiency, prior trauma (including surgery) to the area, and tinea pedis or other toe web abnormalities [65–71], increase the frequency of recurrences. Other predisposing conditions include obesity, tobacco use, a history of cancer, and homelessness [66, 67, 71]. Addressing these factors might decrease the frequency of recurrences, but evidence for any such a

Recurrent SSTIs Preventive educational messages on personal hygiene and appropriate wound care are recommended for all patients with SSTI. Instructions should be provided to: i. Keep draining wounds covered with clean, dry bandages (A-III). ii. Maintain good personal hygiene with regular bathing and cleaning of hands with soap and water or an alcohol-based hand gel, particularly after touching infected skin or an item that has directly contacted a draining wound (A-III).

∅ ∅ Foot Care. Treatment of tinea pedis. Control of eczema. MRSA decolonization (selective)

∅ ∅

27



61)







Nassisi 2012


(score 51)



(N/A)



benefit is sparse. Elevation of the affected area and treatment of predisposing factors, such as edema or underlying cutaneous disorders, are recommended (strong, moderate) In lower-extremity cellulitis, clinicians should carefully examine the interdigital toe spaces because treating fissuring, scaling, or maceration may eradicate colonization with pathogens and reduce the incidence of recurrent infection (strong, moderate). The source of these pathogens is frequently unclear, but in many cases of leg cellulitis, the responsible streptococci reside in macerated, scaly, or fissured interdigital toe spaces [53, 54]. This observation underscores the importance of detecting

iii. Avoid reusing or sharing personal items (eg, disposable razors, linens, and towels) that have contacted infected skin (A-III). Environmental hygiene measures should be considered in patients with recurrent SSTI in the household or community setting: Decolonization may be considered in selected cases if: i. A patient develops a recurrent SSTI despite optimizing wound care and hygiene measures (C-III). ii. Ongoing transmission is occurring among household members or other close contacts despite optimizing wound care and hygiene measures (C-III).

28



61)







Nassisi 2012


(score 51)



(N/A)



and treating tinea pedis, erythrasma, and other causes of toe web abnormalities. Identify and treat predisposing conditions such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities (strong, moderate). These practices should be performed as part of routine patient care and certainly during the acute stage of cellulitis (strong, moderate). Compléments d’information tirés du GPC IDSA 2005: Surgical procedures that increase the risk for cellulitis, presumably due to disruption of lymphatic drainage, include saphenous venectomy [49, 50], axillary node dissection for breast cancer [51, 52], and operations for gynecologic malignancies that

Decolonization strategies should be offered in conjunction with ongoing reinforcement of hygiene measures. Oral antimicrobial therapy is recommended for the treatment of active infection only and is not routinely recommended for decolonization (A-III). An oral agent in combination with rifampin, if the strain is susceptible, may be considered for decolonization if infections recur despite above measures (CIII). In cases where household or interpersonal transmission is suspected: i. Personal and environmental hygiene measures in the patient and contacts are recommended (A-

29



61)







Nassisi 2012


(score 51)



(N/A)



involve lymph node dissection, especially when followed by radiation therapy, such as radical vulvectomy and radical hysterectomy [53, 54].

III). ii. Contacts should be evaluated for evidence of S. aureus infection: a. Symptomatic contacts should be evaluated and treated (A-III); nasal and topical body decolonization strategies may be considered following treatment of active infection (C-III). b. Nasal and topical body decolonization of asymptomatic household contacts may be considered (C-III).

Antibiotiques en prophylaxie Administration of prophylactic antibiotics, such as oral penicillin or erythromycin bid for 4–52 weeks, or intramuscular benzathine penicillin every 2–4 weeks, should be considered in patients who have 3–4 episodes of cellulitis per year despite attempts to treat or control predisposing factors

∅ ∅ ∅ ∅ ∅ ∅

30



61)







Nassisi 2012


(score 51)



(N/A)



(weak, moderate). This program should be continued so long as the predisposing factors persist (strong, moderate). Two randomized trials using twice-daily oral penicillin or erythromycin demonstrated a substantial reduction in recurrences among the antibiotic recipients compared to controls [72, 73]. An observational trial of monthly intramuscular injections of 1.2 million units of benzathine penicillin found that this regimen was beneficial only in the subgroup of patients who had no identifiable predisposing factors for recurrence [74]. In a study of patients with recurrent cellulitis involving arm lymphedema caused by breast cancer treatment, 2.4 million units of biweekly intramuscular

31



61)







Nassisi 2012


(score 51)



(N/A)



benzathine penicillin seemed to reduce the frequency of episodes, but there was no control group [75]. The duration of therapy is indefinite, and infections may recur once prophylaxis is discontinued. For example, a recent double-blind comparative trial demonstrated that phenoxymethyl-penicillin given as 250 mg twice daily for 12 months increased the time to recurrence to 626 days compared with 532 days in the control group and decreased the frequency of recurrence from 37% to 22% [76].

Symptômes These infections cause rapidly spreading areas of erythema, swelling, tenderness, and warmth, sometimes accompanied by lymphangitis and inflammation of the regional lymph nodes.

∅ • Erythema, warmth, edema universally present • Induration or fluctuance (the latter diagnostic of fluid collection) may be present

∅ ∅ Rosenfeld 2015: Patients with a reconfirmed diagnosis of ABRS who fail treatment, especially those with a worsening pattern of illness, should be examined for complications that include orbital or intracranial spread of

∅

32



61)







Nassisi 2012


(score 51)



(N/A)



The skin surface may resemble an orange peel (peau d’orange) due to superficial cutaneous edema surrounding hair follicles and causing skin dimpling because the follicles remain tethered to the underlying dermis. Vesicles, bullae, and cutaneous haemorrhage in the form of petechiae or ecchymoses may develop. Systemic manifestations are usually mild, but fever, tachycardia, confusion, hypotension, and leukocytosis are sometimes present and may occur hours before the skin abnormalities appear. Surgical Site Infections (SSIs) rarely occur during the first 48 hours after surgery, and fever during that period usually arises from noninfectious or

• When first examining, draw a line (mark date/time) around lesion’s borders, if not already present

infection. Suggestive findings on physical examination include proptosis, visual changes, severe headache, abnormal extraocular movements, changes in mental status, and periorbital inflammation, edema, or erythema. Desrosiers 2011: Periorbital cellulitis is seen on CT as soft tissue swelling and manifests as: • orbital pain, • edema, • and high fever. If not aggressively treated, it may spread beyond the orbital septum. Postseptal inflammation involves structures of the orbit with the development of: • proptosis, • limitation of ocular

motion, • pain and

tenderness, • and conjunctival

chemosis.

33



61)







Nassisi 2012


(score 51)



(N/A)



unknown causes. SSIs that do occur in this time frame are almost always due to S. pyogenes or Clostridium species.

A subperiosteal or orbital abscess may result in ophthalmoplegia (globe becomes fixed as a result of extra-ocular muscle paralysis) and diminished visual acuity. A CT scan showing evidence of an abscess, or lack of clinical improvement after 24 to 48 hrs of intravenous antibiotics are indications for surgical exploration and drainage.

Diagnostic différentiel (général) These infections have diverse etiologies that depend, in part, on different epidemiological settings. As a result, obtaining a careful history that includes information about the patient’s immune status, geographic locale, travel history, recent trauma or surgery, previous antimicrobial therapy, lifestyle, hobbies, and

∅ ∅ Evaluation begins with a targeted history and physical examination to elicit the onset of infection, inciting injury, and suggestions of systemic illness.

Patient history: Travel outside Canada, IV drug use, hobbies (fish tank), surgery, previous (90 days) or current antibiotic use, vasculopathy or diabetes, MRSA risk factors. Non-infectious: • DVT • venous stasis, • drug reactions,

∅ ∅

34



61)







Nassisi 2012


(score 51)



(N/A)



animal exposure or bites is essential when developing an adequate differential diagnosis and an appropriate index of suspicion for specific etiological agents. SSTIs in Immunocompromised Patients: In addition to infection, differential diagnosis of skin lesions should include drug eruption, cutaneous infiltration with the underlying malignancy, chemotherapy- or radiation-induced reactions, Sweet syndrome, erythema multiforme, leukocytoclastic vasculitis, and graft-vs-host disease among allogeneic transplant recipients (strong, high). Differential diagnosis for infection of skin lesions should include bacterial, fungal, viral, and parasitic agents (strong, high).

• inflammatory or neoplastic conditions.

35



61)







Nassisi 2012


(score 51)



(N/A)



Compléments d’information tirés du GPC IDSA 2005: Diseases sometimes confused with cellulitis include: acute dermatitis, such as that due to contact with an allergen; gout, with marked cutaneous inflammation extending beyond the joint involved; and herpes zoster. Acute lipodermatosclerosis, a panniculitis that occurs predominantly in obese women with lower extremity venous insufficiency, causes painful, erythematous, tender, warm, indurated, and sometimes scaly areas in the medial leg that resemble cellulitis [72].

Diagnostic différentiel (abcès) The term “cellulitis” is not appropriate for cutaneous inflammation associated with collections of pus, such as in septic bursitis, furuncles, or skin abscesses.

∅ An abscess is a cavity filled with pus that results from a bacterial infection. An abscess in the subcutaneous tissues can be present with or without surrounding

∅ ∅ ∅ ∅

36



61)







Nassisi 2012


(score 51)



(N/A)



cellulitis.

Diagnostic différentiel (fasciite nécrosante) A distinguishing clinical feature [of necrosing fasciitis] is the wooden-hard induration of the subcutaneous tissues. In cellulitis, the subcutaneous tissues are palpable and yielding; in fasciitis the underlying tissues are firm, and the fascial planes and muscle groups cannot be discerned by palpation.

∅ Signs of possible necrotizing infection: • Very rapid spread • Bluish discoloration, blistering, pain out of proportion or beyond the edges of the lesion, skin anesthesia, rapid progression, or gas in the tissue • These signs sometimes appear late in course

Severe, deep soft-tissue and necrotizing infections must be considered, including recognition of the following: • Pain disproportionate to physical findings • Violaceous bullae • Cutaneous hemorrhage • Skin sloughing • Skin anesthesia • Rapid progression • Gas in the soft tissues The above laboratory results (i.e. complete blood cell count with differential, electrolytes and creatinine, bicarbonate, creatinine phosphokinase, and C-reactive protein levels) can also be used to calculate the Laboratory Risk Indicator for

∅ ∅ ∅

37



61)







Nassisi 2012


(score 51)



(N/A)



Necrotizing Fasciitis (LRINEC) score. The LRINEC score has not been prospectively validated, and the ability to identify necrotizing fasciitis early in its clinical course when it is not already apparent on history and physical examination is unproven.48,49

Critères d’évaluation de la sévérité de l’infection Nonpurulent SSTIs. [ici, non-purulent = pas d’abcès] Mild infection: typical cellulitis/erysipelas with no focus of purulence. Moderate infection: typical cellulitis/erysipelas with systemic signs of infection. Severe infection: patients who have failed oral antibiotic treatment or those with systemic signs of infection, or those who are immunocompromised, or those with clinical signs of deeper infection such as

∅ ∅ ∅ • Non-SIRS / Pre-SIRS

SIRS= Systemic Inflammatory Response Syndrome • SIRS / Sepsis (2 of

4)

>38.3 <36.0; Heart Rate >90; Respiratory Rate>20 or PaCO2<32; White Blood Cells <4 >12 or Bands • Severe Sepsis (1 of

7+)

Mottled, anuria, Lactate>2, Plt<100, DIC, ARDS, fastΔLOC…

∅ ∅

38



61)







Nassisi 2012


(score 51)



(N/A)



bullae, skin sloughing, hypotension, or evidence of organ dysfunction. Purulent skin and soft tissue infections (SSTIs) - abcsess. Mild infection: for purulent SSTI, incision and drainage is indicated. Moderate infection: patients with purulent infection with systemic signs of infection. Severe infection: patients who have failed incision and drainage plus oral antibiotics or those with systemic signs of infection or immunocompromised patients. Systemic signs of infection: temperature >38°C, tachycardia (heart rate >90 beats per minute), tachypnea (respiratory rate >24 breaths per minute) or abnormal white blood cell count (>12 000 or <4 000 cells/μL),

• Septic Shock

(Pressors)

Refractory Septic Sh. (More Pressors)

Critères d’hospitalisation

39



61)







Nassisi 2012


(score 51)



(N/A)



Outpatient therapy is recommended for patients who do not have: • SIRS, • altered mental

status, • or hemodynamic

instability (mild nonpurulent; Figure 1) (strong, moderate). Hospitalization is recommended: • if there is concern

for a deeper or necrotizing infection,

• for patients with poor adherence to therapy,

• for infection in a severely immunocompromised patient,

• or if outpatient treatment is failing

(moderate or severe nonpurulent; Figure 1) (strong, moderate)

For patients with systemic toxicity and/or rapidly progressive or worsening infection despite receipt of appropriate oral antibiotics, inpatient management and surgical intervention is recommended.

Patients who should be admitted: • Are systemically ill (ill-appearance, persistent fevers, hemodynamic instability etc.) • Are unable to tolerate oral therapy • Fail appropriate outpatient therapy (48 hours of treatment and not showing signs of improvement) • Have rapidly progressive lesions • Need pain control or wound care • Consider if < 6 months of age • Adequate follow up not available (LC)

In patients with hypotension and/or one of the following abnormalities, consider hospitalization and surgical consultation for inspection, exploration, and/or drainage: • Elevated

creatinine level • Low serum

bicarbonate level • Elevated

creatinine phosphokinase level (2-3 times the upper limit of normal)

• Marked left shift • C-reactive protein

level > 13 mg/L

∅ Wald 2013: Complications of Acute Bacterial Sinusitis Similarly, if proptosis, impaired visual acuity, or impaired and/or painful extraocular mobility is present on examination, the patient should be hospitalized, and a contrast-enhanced CT should be performed.

∅

Tests diagnostiques Cultures of blood or cutaneous aspirates, biopsies, or swabs are not routinely

Cultures from abscesses and other purulent SSTIs are recommended (A-

• Obtain wound cultures when possible; i.e., in patients who have

Patients with systemic signs of toxicity may warrant the following

∅ Desrosiers 2011: Maxillary Sinus Aspirate (MSA) MSA is recommended if there

∅

40



61)







Nassisi 2012


(score 51)



(N/A)



recommended (strong, moderate). Blood cultures are generally positive in ≤5% of cases [38]. The yield of cultures of needle aspirations of the inflamed skin ranges from ≤5% to approximately 40% [39–46]. Cultures of punch biopsy specimens yield an organism in 20%–30% of cases [39, 47], but the concentration of bacteria in the tissues is usually quite low [47]. Cultures of blood are recommended (strong, moderate), and cultures and microscopic examination of cutaneous aspirates, biopsies, or swabs should be considered in patients with: • malignancy on

chemotherapy, • neutropenia, • severe cell-

mediated immunodeficiency,

• immersion injuries, • and animal bites (weak, moderate).

III): • in patients treated

with antibiotic therapy,

• in patients with severe local infection or signs of systemic illness,

• in patients who have not responded adequately to initial treatment,

• and if there is concern for a cluster or outbreak.

In nonpurulent cellulitis (cellulitis with no purulent drainage or exudate and no associated abscess), ultrasound may be considered to exclude occult abscess [126, 127].

spontaneously draining lesions and in patients who undergo I&D procedures (Liu ⊕⊕, LC) • Routine blood testing (CBC, CRP, blood culture) is not necessary for most children with SSTI (Stevens ⊕, LC) • Obtain a CBC, CRP, and blood cultures in children with signs of systemic toxicity, including ill-appearance, rapidly spreading lesions, persistent fevers, and age <1yo (Liu ⊕, Stevens ⊕, LC) • Use bedside ultrasound where available to improve the accuracy in diagnosis of subcutaneous abscesses (Squire ⊕⊕⊕, Tayal ⊕⊕⊕)

diagnostic tests: • blood culture and

susceptibility, • complete blood

cell count with differential,

• electrolytes and creatinine,

• bicarbonate, • creatinine

phosphokinase, • and C-reactive

protein levels. In patients with hypotension and/or one of the following abnormalities, consider hospitalization and definitive etiologic diagnosis via Gram stain, culture of needle aspiration or punch biopsy, and surgical consultation for inspection, exploration, and/or drainage: • Elevated

creatinine level • Low serum

bicarbonate level • Elevated

creatinine phosphokinase level (2-3 times

are serious complications, such as orbital infection, intracranial extension of the infection, or in patients with nosocomial sinusitis. Because the procedure is invasive, it is usually performed by specialists rather than in family practice, and even then only rarely. Chow 2012: In patients with ABRS suspected to have suppurative complications, obtaining axial and coronal views of contrastenhanced CT rather than MRI is recommended for localization of infection and to guide further treatment (weak, low). Suppurative complications of ABRS are rare, estimated to be 3.7%–11% among hospitalized pediatric patients with sinusitis, and are primarily related to orbital cellulitis and intracranial extension

41



61)







Nassisi 2012


(score 51)



(N/A)



SSTIs in Immunocompromised Patients : Biopsy or aspiration of the lesion to obtain material for histological and microbiological evaluation should always be implemented as an early diagnostic step (strong, high). Compléments d’information tirés du GPC IDSA 2005: it is the recommendation of this committee that patients with soft-tissue infection accompanied by signs and symptoms of systemic toxicity (e.g., fever or hypothermia, tachycardia [heart rate, >100 beats/min], and hypotension [systolic blood pressure, <90 mm Hg or 20 mm Hg below baseline]) have blood drawn to determine the following laboratory parame ters: results of blood culture

the upper limit of normal)

• Marked left shift • C-reactive protein

level > 13 mg/L Ultrasonography can be a useful adjunct to help identify deep abscesses, differentiate cellulitis from an abscess, and guide drainage.

of infection [201]. The recommendation of the IDSA panel in favor of contrast enhanced CT over MRI places greater value on relative availability and speed of diagnosis by CT, and a lack of need for sedation, which is frequently required for MRI studies in infants and children. Wald 2013: Similarly, if proptosis, impaired visual acuity, or impaired and/or painful extraocular mobility is present on examination, the patient should be hospitalized, and a contrast-enhanced CT should be performed.

42



61)







Nassisi 2012


(score 51)



(N/A)



and drug susceptibility tests, complete blood cell count with differential, and creatinine, bicarbonate, creatine phosphokinase, and C-reactive protein levels. In patients with hypotension and/or an elevated creatinine level, low serum bicarbonate level, elevated creatine phosphokinase level (2–3 times the upper limit of normal), marked left shift, or a C-reactive protein level >13 mg/L, hospitalization should be considered and a definitive etiologic diagnosis pursued aggressively by means of procedures such as Gram stain and culture of needle aspiration or punch biopsy specimens, as well as requests for a surgical consultation for inspection, exploration, and/or drainage.

Facteurs de risque pour SARM • purulent drainage, • penetrating trauma

∅ History in the last 6 months of: • MRSA in the patient

∅ ∅ ∅ Dumaresq 2016, CISSS Chaudière-Appalaches :

43



61)







Nassisi 2012


(score 51)



(N/A)



(especially from illicit drug use),

• or concurrent evidence of MRSA infection elsewhere.

• MRSA in the family • Recurrent boils, pustules, “spider bites”, etc. that required antibiotics, in patient or family

FACTEURS DE RISQUE MAJEURS ASSOCIÉS AU SARM-C • Jeune âge (enfants et jeunes adultes) • Drogue intraveineuse • Sports de contact • Premières nations • Incarcération • Personnel militaire • Homme ayant des relations sexuelles avec d’autres hommes (HARSAH) et VIH • Infection/colonisation antérieure

Principes de traitement Traitements de soutien

Elevation of the affected area and treatment of predisposing factors, such as edema or underlying cutaneous disorders, are recommended (strong, moderate). Elevation of the affected area hastens improvement by promoting gravity

∅

∅ ∅ ∅ ∅ Dumaresq 2016, CISSS Chaudière-Appalaches : La surélévation du membre atteint, les bas de compression lorsque tolérés et l’utilisation d’anti-inflammatoires (en l’absence de contre-indication) sont des mesures

44



61)







Nassisi 2012


(score 51)



(N/A)



drainage of edema and inflammatory substances. Systemic corticosteroids (eg, prednisone 40 mg daily for 7 days) could be considered in nondiabetic adult patients with cellulitis (weak, moderate). Treating the inflammation in these infections by combining antimicrobial therapy with either a nonsteroidal anti-inflammatory agent (ibuprofen 400 mg 4 times daily [qid] for 5 days) or systemic corticosteroids significantly hastens clinical improvement compared with antimicrobial therapy alone [60, 61]. A randomized, double-blind, placebo-controlled trial involving 108 adult nondiabetic patients, demonstrated that an 8-day course of oral corticosteroids in combination with antimicrobial therapy

thérapeutiques adjuvantes très importantes.

45



61)







Nassisi 2012


(score 51)



(N/A)



led to a significantly more rapid clinical resolution of cellulitis (primarily of the legs) than antimicrobial therapy alone [61, 62]. Long-term follow-up of these patients showed no difference in relapse or recurrence [61, 62]. The benefits of systemic corticosteroids in this situation are consistent with their efficacy and safety as adjunctive treatment in other infections [63]. The clinician must ensure that a deeper infection such as necrotizing fasciitis is not present. Most patients can receive treatment without hospitalization [63, 64]. Hospitalization is indicated for suspicion of necrotizing infection or for patients with severe systemic features, such as fever, delirium, or hypotension. Other indications include poor response to outpatient therapy, severe immunocompromise,

46



61)







Nassisi 2012


(score 51)



(N/A)



and problems with a patient’s adherence to treatment. Larger clinical trials should determine if anti-inflammatory agents are useful or detrimental in the treatment of cellulitis and erysipelas. Should Tetanus Toxoid Be Administered for Animal Bite Wounds? Tetanus toxoid should be administered to patients without toxoid vaccination within 10 years. (strong, low). Although no recent cases of tetanus from a bite have been reported, dogs and cats are coprophagic and could potentially transmit tetanus. Administering tetanus vaccine/toxoid after animal bite wounds is predicated upon the Advisory Committee on Immunization Practices (ACIP) recommendations [142]. The benefits of regular tetanus toxoid

47



61)







Nassisi 2012


(score 51)



(N/A)



boosters in adults who have had a primary series have been questioned although its use in “dirty wounds” seems sensible [161, 162]. Persons who have not completed the vaccine series should do so. A booster dose of tetanus toxoid vaccine should be administered for dirty wounds if >5 years has elapsed since the last dose and for clean wounds, if >10 years.

What Is the Role of Preemptive Antimicrobial Therapy to Prevent Infection for Dog or Cat Bites? Numerous studies highly variable in quality and employing diverse and non-standardized approaches to basic wound care and a variety of antimicrobial agents, have failed to definitively determine who should receive early, preemptive therapy for bite wounds. Consequently, the decision to give

48



61)







Nassisi 2012


(score 51)



(N/A)



“prophylactic” antibiotics should be based on wound severity and host immune competence [147, 148]. Preemptive early antimicrobial therapy for 3–5 days is recommended for patients who (a) are immunocompromised, (b) are asplenic, (c) have advanced liver disease, (d) have pre-existing or resultant edema of the affected area, (e) have moderate to severe injuries, especially to the hand or face, or (f) have injuries that may have penetrated the periosteum or joint capsule (strong, low). Postexposure prophylaxis for rabies may be indicated; consultation with local health officials is recommended to determine if vaccination should be initiated (strong, low). The need for rabies prophylaxis and/or therapy should be addressed.

49



61)







Nassisi 2012


(score 51)



(N/A)



Incision et drainage (abcès) En presence d’abcès: Incision and drainage is the recommended treatment for inflammed epidermoid cysts, carbuncles, abscesses, and large furuncles (strong, high). The decision to administer antibiotics directed against S. aureus as an adjunct to incision and drainage should be made based on the presence or absence of systemic inflammatory response syndrome (SIRS) such as temperature >38°C or <36°C, tachypnea >24 breaths per minute, tachycardia >90 beats per minute, or white blood cell count >12 000 or <4 000 cells/μL (moderate; Figure 1) (strong, low). An antibiotic active against MRSA is recommended for patients with carbuncles or abscesses who have markedly impaired host defenses and in

For a cutaneous abscess, incision and drainage is the primary treatment (A-II). Antibiotic therapy is recommended for abscesses associated with the following conditions: • severe or

extensive disease (eg, involving multiple sites of infection)

• or rapid progression in presence of associated cellulitis,

• signs and symptoms of systemic illness,

• associated comorbidities or immunosuppression,

• extremes of age, • abscess in an

area difficult to drain (eg, face, hand, and genitalia),

• associated septic

No drainage is needed for abscesses <1 cm on bedside ultrasound; these patients may be discharged home on antibiotics alone with close PCP follow-up (Tayal ⊕, LC) Larger abscesses require thorough I&D of purulent material with adequate sedation and analgesia No oral antibiotics are needed for simple abscesses that have been incised and drained completely, (Duong ⊕⊕⊕, Chen ⊕⊕, Paydar ⊕⊕, and Hankin ⊕) unless the patient has one of the following: • Severe or extensive disease • Rapid progression in presence of associated cellulitis • Signs and symptoms of systemic illness

Effective treatment of abscesses entails incision, thorough evacuation of the pus, and probing the cavity to break up loculations (A-I). Gram stain, culture, and systemic antibiotics are rarely indicated unless there is extensive surrounding cellulitis, fever, multiple lesions, severely impaired host defenses, or cutaneous gangrene. (E-III)

∅ ∅ Dumaresq 2016, CISSS Chaudière-Appalaches : ABCÈS CUTANÉ : QUAND CULTIVER ET TRAITER ? • Abcès > 5 cm • Abcès multiples/récurrents • Cellulite adjacente extensive • Comorbidités ou immunosuppression • Signes systémiques d’infection • Absence d’amélioration suite au drainage

50



61)







Nassisi 2012


(score 51)



(N/A)



patients with SIRS (Figure 1, Table 2) (strong, low). The addition of systemic antibiotics to incision and drainage of cutaneous abscesses does not improve cure rates [17, 21, 22, 24, 25], even in those due to MRSA, but did have a modest effect on the time to recurrence of other abscesses [17, 25]. However, systemic antibiotics should be given to patients: • with severely

impaired host defenses

• or signs or symptoms of systemic infection (Figure 1, Table 2).

In addition: • multiple abscesses, • extremes of age, • and lack of

response to incision and drainage alone

are additional settings in which systemic antimicrobial therapy should be considered. The most important therapy for an SSI

phlebitis, • and lack of

response to incision and drainage alone (A-III).

For hospitalized patients with complicated SSTI (cSSTI; defined as patients with deeper soft-tissue infections, surgical/ traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns), surgical debridement should be considered.

• Associated comorbidities or immunosuppression • Extremes of age (<1 year old) • Abscess in area difficult to drain (face, hand, and genitalia) • Associated septic phlebitis • Lack of response to I &D alone (Liu ⊕⊕) Prescribe oral clindamycin for outpatient treatment of abscesses that could not have an adequate I&D, or do not meet low-risk criteria as summarized below (Liu ⊕⊕): • Age ≥ 1 year • No fever • Well-appearing • Adequate I&D • No significant comorbidities

51



61)







Nassisi 2012


(score 51)



(N/A)



[surgical site infection] is to open the incision, evacuate the infected material, and continue dressing changes until the wound heals by secondary intention. Suture removal plus incision and drainage should be performed for surgical site infections (strong, low).

Antibiothérapie (cellulite légère) Non-purulent (Necrotizing infection/ Cellulitis/ Erysipelas): Mild (Oral Rx) • Penicillin VK (250–

500 mg every 6 h po) or

• Cephalosporin (Cephalexin 500 mg every 6 h PO; pediatric dose= 25–50 mg/kg/d 4 divided doses PO) or

• Dicloxacillin (500 mg qid PO; pediatric dose= 25–50 mg/kg/d in 4 divided doses PO) or

• Clindamycin (300–450 mg qid PO; pediatric dose= 25–

Outpatients with nonpurulent cellulitis (eg, cellulitis with no purulent drainage or exudate and no associated abscess): Empirical therapy for infection due to b-hemolytic streptococci is recommended (A-II). • b-lactam (eg,

cephalexin and dicloxacillin) 500 mg PO QID (A-II)

The role of CA-MRSA is unknown. Empirical coverage for CA-MRSA is recommended in

Discharged patients Antibiotics for nonpurulent cellulitis: For outpatient treatment of simple cellulitis without an abscess, drainage, history of drainage, or failure of outpatient antibiotic course (>48 h on appropriate antibiotics) (Liu ⊕⊕⊕, Stevens ⊕⊕, Elliott ⊕⊕, and Williams ⊕⊕): • oral beta-lactam (cephalexin) For cellulitis that has not responded to anti-MSSA therapy (beta

Outpatient treatment: Penicillin, either orally or parenterally, is the treatment of choice for erysipelas. (A-I) Empiric therapy for Streptococcus pyogenes (beta-hemolytic streptococcus) is recommended: • Cephalexin 500

mg PO 4 times daily x 7-10 days

• Dicloxacillin 500 mg PO 4 times daily x 7-10 days

If severe penicillin

Non-SIRS / Pre-SIRS:

One of the following three:

• Cephalexin 500 mg PO QID

• Cloxacillin 500 mg PO QID

• Cefadroxil 500-1000 mg PO BID (if drug coverage available)

If in ER, going home, and poor tissue penetration is a concern:

• Load with either:

• Cefazolin 2g IV x1 PLUS Probenecid 2g PO x 1 (avoid if

∅ Dumaresq 2016, CISSS Chaudière-Appalaches : Pour le traitement des infections cutanées comme la cellulite, il faut favoriser l’utilisation de la cloxacilline ou des céphalosporines de 1ère génération telles que la céphalexine orale, céfadroxil orale ou céfazoline intraveineuse. La faible sensibilité à la clindamycine (75 %) parmi les souches de S. aureus est préoccupante. La

52



61)







Nassisi 2012


(score 51)



(N/A)



30 mg/kg/d in 3 divided doses PO)

Purulent (Furuncle / Carbuncle / Abscess) Mild No antibiotics Typical cases of cellulitis without systemic signs of infection should receive an antimicrobial agent that is active against streptococci (mild; Figure 1) (strong, moderate). A large percentage of patients can receive oral medications from the start for typical cellulitis [56], and suitable antibiotics for most patients include penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin. The recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within

patients who do not respond to b-lactam therapy and may be considered in those with systemic toxicity. Five to 10 days of therapy is recommended but should be individualized on the basis of the patient’s clinical response. Purulent cellulitis (defined as cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess): Empirical therapy for CA-MRSA is recommended pending culture results. Empirical therapy for infection due to b-hemolytic streptococci is likely to be unnecessary (A-II). For empirical coverage of CA-

lactam, >48 hours) (Liu ⊕, LC): • oral clindamycin Antibiotics for purulent cellulitis: For outpatient treatment of purulent cellulitis (Liu ⊕, LC): • oral clindamycin For inpatient treatment of cellulitis in patients who have failed antibiotic therapy that covers MRSA (Liu ⊕⊕): • IV vancomycin Patients should complete 7-10 total days of antibiotic treatment. (LC, Liu ⊕). Antibiotic treatment can be extended by the PCP (Primary Care Physician) if the lesion is not completely resolved at the end of this course. Treatment failure occurs if there is: • Significant or rapid

allergy: • Azithromycin 500

mg PO x 1 dose than 250 mg PO daily x 4 days or

• Clindamycin 300 mg PO 3 times daily x 7-10 days.

If comorbidities, purulent drainage, or in critical anatomic location, add empiric coverage for CA-MRSA: • Doxycycline or

minocycline 100 mg PO twice daily x 7-10 days

• Trimethoprim-sulfamethoxazole 160/800 mg PO 1-2 tabs twice daily x 7-10 days

• Clindamycin 300 mg PO 3 times daily x 7-10 days

Note: Clindamycin is bacteriostatic, potential for cross-resistance and emergence of resistance in erythromycin-resistant strains;

CrCl <40) or • Ceftriaxone 1-2g IV

x 1

If concern for MRSA:

Add TMP/SMX 1-2 DS tablets PO BID

If severe PCN allergy:

Clindamycin 300 mg PO QID PLUS

TMP/SMX 1-2 DS tablets PO BID

OR

Doxycycline 200 mg PO x 1 then 100 mg PO BID)

Ceftriaxone was previously thought to be a poor choice, but has reasonable Staphylococcus aureus coverage (except if MRSA or if bacteremia, endocarditis, or osteomyelitis is a concern). Dosage for ceftriaxone may need to be modified (increased frequency and or dose).

clindamycine n’est donc pas un antibiotique de premier choix pour le traitement des cellulites puisque la résistance est élevée et parce qu’elle est fréquemment associée aux infections à Clostridium difficile. La clindamycine n’est pas un antibiotique de premier choix pour le traitement des cellulites puisque la résistance est fréquente parmi les streptocoques bêta-hémolytiques et parce qu’elle est fréquemment associée aux infections à Clostridium difficile. Les streptocoques du groupe A (Streptococcus pyogenes) et du groupe B (S. agalactiae) demeurent universellement

53



61)







Nassisi 2012


(score 51)



(N/A)



this time period (strong, high). In cases of uncomplicated cellulitis, a 5-day course of antimicrobial therapy is as effective as a 10-day course, if clinical improvement has occurred by 5 days [57].

MRSA in outpatients with SSTI, oral antibiotic options include the following: • clindamycin

(300–450 mg PO TID; pediatric dose= 10–13 mg/kg/dose PO every 6–8 h, not to exceed 40 mg/kg/day) (A-II)

• TMP-SMX (1–2 DS tab PO BID; pediatric dose= Trimethoprim 4–6 mg/kg/dose, sulfamethoxazole 20–30 mg/kg/dose PO every 12 h) (A-II)

• Doxycycline (100 mg PO BID; pediatric dose= ≤45kg: 2 mg/kg/dose PO every 12 h, >45kg: adult dose) (A-II)

• Minocycline (200 mg x 1, then 100 mg PO BID; pediatric dose= 4 mg/kg PO x 1,

expansion of cellulitis at any point in the course of treatment (i.e. more than just one or two centimeters beyond margins), or • Cellulitis is not showing improvement after 48 hours of effective antibiotic treatment (LC) • The development of a new abscess within an area of previous infection while on antibiotics does not in and of itself constitute treatment failure

inducible resistance in MRSA For cellulitis, a penicillinase-resistant semisynthetic penicillin or a first-generation cephalosporin should be selected unless streptococci or staphylococci resistance is common in the community. (A-I)

Macrolides (e.g. clarithromycin, azithromycin) are listed as a treatment option in penicillin allergic patients with mild cellulitis/erysipelas in a number of other references (Johns Hopkins, Sanford, Capital Health NS). However, due to significant resistance in PEI, macrolides are not included as an option in these empiric treatment guidelines.

Clindamycin has very good Group A Streptococcus coverage (91%) yet for Staphylococcus aureus infections the susceptibility rate is 68% (Health PEI Antibiogram 2012). Therefore in severe penicillin allergic patients with minor disease:

Clindamycin

PLUS

sensibles à la pénicilline et aux céphalosporines. De 10 à 14% des souches de S. aureus isolées de spécimens cliniques sont des SARM. Les tétracyclines (doxycycline, minocycline) et la combinaison triméthoprime-sulfaméthoxazole (TMP-SMX) demeurent très actives contre nos souches de SARM (95 % et 98 % de sensibilité respectivement). Toutes nos souches étaient sensibles à la vancomycine pour la période analysée. Si une infection cutanée présente des caractéristiques associées aux souches de SARM d’origine communautaire (SARM-C), comme par exemple des furoncles ou abcès

54



61)







Nassisi 2012


(score 51)



(N/A)



then 2 mg/kg/dose PO every 12 h) (A-II),

• Linezolid (600 mg PO BID; pediatric dose= 10 mg/kg/dose PO every 8 h, not to exceed 600 mg/dose) (A-II).

Notes: • Clyndamycin =

Clostridium difficile–associated disease may occur more frequently, compared with other oral agents.

• TMP-SMX is pregnancy category C/D and not recommended for women in the third trimester of pregnancy and for children <2 months of age.

• Tetracyclines are not recommended

Anti-Staphylococcal treatment (TMP/SMX or doxycycline)

However, clindamycin is one of the antibiotics associated with the highest risk of Clostridium difficile infection (CDI). Buffie et al. demonstrated that a single dose of clindamycin markedly reduces the diversity of the intestinal microbiota of mice for at least 28 days, with an enduring loss of ~90% of normal microbial taxa from the cecum which resulted in sustained susceptibility to Cdiff-induced colitis. Caution is recommended when using clindamycin, especially if the patient has a history of a previous CDI.

A once daily cefazolin/probenecid combination is convenient to administer as outpatient antimicrobial therapy for

spontanés, l’utilisation de doxycycline ou de TMP-SMX est à privilégier si une antibiothérapie est requise, avec comme alternative la clindamycine puisque la majorité des souches de SARM-C sont sensibles à la clindamycine (contrairement aux souches de SARM associées aux soins de santé). La combinaison de TMP-SMX ne couvre toutefois pas les streptocoques bêta-hémolytiques. Une durée de traitement de 5 jours pour la cellulite est suffisante s’il y a eu amélioration clinique (mais pas nécessairement résolution complète des signes inflammatoires). Ainsi, il est raisonnable de prescrire d’emblée 5

55



61)







Nassisi 2012


(score 51)



(N/A)



for children under 8 years of age (A-II) and are pregnancy category D.

Five to 10 days of therapy is recommended but should be individualized on the basis of the patient’s clinical response. If coverage for both b-hemolytic streptococci and CA-MRSA is desired, options include the following: • Clindamycin

300–450 mg PO TID (pediatric dose= 10–13 mg/kg/dose PO every 6–8 h, not to exceed 40 mg/kg/day) (A-II)

• b-lactam (eg, amoxicillin 500 PO mg TID)

AND/OR TMP-SMX (1–2 DS tab PO BID; pediatric dose= Trimethoprim 4–6

empiric treatment of moderate SSTI. Pharmacokinetic data and available clinical information suggests that a cefazolin/probenecid regimen is effective for treatment of SSTI. Probenecid has been shown to inhibit the tubular secretion of cefazolin, thereby prolonging the half-life and serum concentration of cefazolin. Cefazolin/probenecid provides narrow-spectrum antimicrobial coverage, theoretically limiting the development of antimicrobial resistance.12

jours de traitement en avisant le patient de consulter à nouveau s’il n’y a aucune amélioration en l’espace de 3 jours. Tétrault 2016, INSPQ/LSPQ : La proportion de souches de SARM parmi le nombre total de Staphylococcus aureus isolés de pus superficiels et pus profonds de la peau et des tissus mous de patients provenant de la communauté est de 10 %. Ce taux varie de 4 à 15 % selon les régions, en excluant les régions «Nunavik, Baie James» Parmi les nouveaux cas de SARM, 77 % ont un profil communautaire et 23 % ont un profil hospitalier. Inversement, parmi

56



61)







Nassisi 2012


(score 51)



(N/A)



mg/kg/dose, sulfamethoxazole 20–30 mg/kg/dose PO every 12 h) OR Doxycycline (100 mg PO BID; pediatric dose= ≤45kg: 2 mg/kg/dose PO every 12 h, >45kg: adult dose) OR Minocycline (200 mg x 1, then 100 mg PO BID; pediatric dose= 4 mg/kg PO x 1, then 2 mg/kg/dose PO every 12 h) (A-II) • Linezolid (600

mg PO BID; pediatric dose= 10 mg/kg/dose PO every 8 h, not to exceed 600 mg/dose) (A-II)

Linezolid is FDA-approved for SSTI but is not superior to less expensive alternatives [119].

les cas connus porteurs, 54 % ont un profil communautaire et 46 % ont un profil hospitalier (p-value < 0.05). La sensibilité globale des SARM est de 100 % à la vancomycine, à la daptomycine, à la rifampicine et au TMP-SMX et de 99 % à la doxycycline et au linézolide. La sensibilité globale à la clindamycine est de 62 %, mais hautement variable entre les profils communautaires et hospitaliers (SARM-AC = 83 %; SARM-AH = 22 %). La sensibilité à l’érythromycine est de 28 % pour les SARM-AC et de 15 % les SARM-AH. Données québécoises sur les Streptocoques de groupe A invasifs (Bélanger 2012) :

57



61)







Nassisi 2012


(score 51)



(N/A)



Dans le cadre du PSER (Programme de surveillance épidémiologique rehaussée) effectué en laboratoire du 18 janvier 2009 au 17 janvier 2011, aucune des 446 souches invasives à SGA inscrites dans le fichier du LSPQ n’a démontré de résistance à la pénicilline, à la vancomycine, à la ceftriaxone ou à la lévofloxacine, mais 59 de ces souches (13,2 %) ont exprimé un phénotype de résistance à la fois à l’érythromycine et à la clindamycine. La majorité des souches résistantes (51/59) ont présenté la forme inductible. 14 souches résistantes ont été identifiées parmi les 106 souches isolées de cas de cellulite/érysipèle (13,2%).

58



61)







Nassisi 2012


(score 51)



(N/A)



Demczuk 2015, ASPC : Infection invasive à Streptococcus pyogenes (streptocoque du groupe A) : Parmi les 1 443 isolats invasifs de S. pyogenes analysés, seuls 2 isolats n’étaient pas sensibles au chloramphénicol (0,1%), alors que ce nombre était de 36 (9,4 %) en 2010. La résistance à l’érythromycine a poursuivi sa chute, étant passée de 14,4 % (n = 55) en 2010 à 6,9 % (n = 100, p<0.001) en 2014; quant à la résistance à la clindamycine [constitutive], elle est demeurée relativement inchangée, s’établissant à 2,8 % (n = 40) en 2014

59



61)







Nassisi 2012


(score 51)



(N/A)



(figure 38, tableau 13). Une résistance induite à la clindamycine a été notée chez 3,7 % (n = 53) des isolats. Aucune résistance à la pénicilline ou à la vancomycine n’a été constatée. Infection invasive à Streptococcus agalactiae (streptocoque du groupe B) : Parmi les 249 isolats invasifs de S. agalactiae analysés par diffusion sur gélose avec disques en 2014, 1 isolat était résistant au chloramphénicol (sérotype V). La résistance à l’érythromycine et à la clindamycine est demeurée relativement inchangée, ayant été observée respectivement chez 49,4 % (n = 123) et 27,3 % (121) des

60



61)







Nassisi 2012


(score 51)



(N/A)



isolats analysés en 2014 (figure 42, tableau 17).

Antibiothérapie (cellulite modérée) Non-purulent (Necrotizing infection/ Cellulitis/ Erysipelas): Moderate (Intravenous Rx) • Penicillin (2–4

million units every 4–6 h IV; pediatric dose= 60–100 000 units/kg/ dose every 6 h) or

• Ceftriaxone or • Cefazolin (1 g every

8 h IV; pediatric dose= 33 mg/kg/dose every 8 h IV) or

• Clindamycin (600–900 mg every 8 h IV; pediatric dose= 10–13 mg/kg dose every 8 h IV)

Purulent (Furuncle / Carbuncle / Abscess): Moderate Empiric Rx • TMP/SMX (1–2

doublestrength tablets bid PO;

A b-lactam antibiotic (eg, cefazolin) may be considered in hospitalized patients with nonpurulent cellulitis with modification to MRSA-active therapy if there is no clinical response [135] (A-II). The use of rifampin as a single agent or as adjunctive therapy for the treatment of SSTI is not recommended (A-III). Because of the likely development of resistance, rifampin should not be used as monotherapy for the treatment of MRSA infections. The adjunctive use of rifampin with another active drug for the treatment of SSTI is not recommended in the

Admitted patients Antibiotics for nonpurulent cellulitis: For inpatient treatment of simple cellulitis without an abscess, drainage, history of drainage, or failure of outpatient antibiotic course (>48 h on appropriate antibiotic) (Liu ⊕⊕⊕ and Stevens ⊕⊕) • IV beta lactam (cefazolin) For inpatient treatment of cellulitis in patients who are systemically ill (fever >38, tachycardia, vomiting) or have failed an outpatient antibiotic course that covers MRSA (Liu ⊕) • IV vancomycin Antibiotics for purulent cellulitis: For inpatient treatment of purulent cellulitis or

Inpatient Treatment: Empiric therapy for Streptococcus pyogenes and CA-MRSA is recommended. Beta-hemolytic Streptococcus and MSSA Coverage: • Nafcillin 2 g IV q4

hours • Oxacillin 2 g IV

q4 hours • Cefazolin 1 g IV

q8 hours • Ceftriaxone 1-2 g

IV q24 hours • Cefotaxime 1-2 g

IV q8 hours • Clindamycin 600

mg IV q8 hours CA-MRSA Coverage • Clindamycin 600

mg IV q8 hours • Linezolid 600 mg

IV q12 hours • Vancomycin 15

mg/kg IV q12 hours

SIRS / Sepsis:

Cefazolin 2g IV x 1 dose then 1g (<70kg) or 2g (≥70kg) IV q8h

If outpatient:

• Cefazolin 2g IV + Probenecid 1-2g PO q24h (avoid if CrCl <40) OR

• Ceftriaxone 2g IV x 1 dose then 1g (<70kg) or 2g (≥70kg) IV q24h

If severe PCN allergy or MRSA suspected:

Vancomycin 25 mg/kg IV load, then 15 mg/kg IV q12h or consult ID for outpatient options.

If foul smelling: ADD Metronidazole 500 mg PO/IV q12h for anaerobic coverage.

∅ Vincent 2013, CHU Ste-Justine : Il est difficile actuellement de justifier l’utilisation de la cetriaxone, alors que nous disposons de données rassurantes sur la pharmacocinétique/ pharmacodynamique de la céphalexine orale, si ce n’est que pour les patients où la voie orale n’est pas possible, dans le cas d’un patient avec des vomissements par exemple. Nous favorisons la céphalexine per os à forte dose (90‐100 mg/kg/jour) comme traitement initial des cellulites modérées qui seront suivi au Centre de jour.

61



61)







Nassisi 2012


(score 51)



(N/A)



pediatric dose= 8–12 mg/kg (based on trimethoprim component) in either 4 divided doses IV or 2 divided doses po) or

• Doxycycline (100 mg bid po; Not recommended for age <8 yd)

Defined Rx MRSA • TMP/SMX (1–2

doublestrength tablets bid PO; pediatric dose= 8–12 mg/kg (based on trimethoprim component) in either 4 divided doses IV or 2 divided doses po)

MSSA • Dicloxacillin (500

mg qid PO; pediatric dose= 25–50 mg/kg/d in 4 divided doses PO) or

• Cephalexin (500 mg every 6 h PO; pediatric dose= 25–50 mg/kg/d 4 divided doses PO)

absence of data to support benefit [120]. Seven to 14 days of therapy is recommended but should be individualized on the basis of the patient’s clinical response.

cellulitis that has not responded to anti-MSSA therapy (beta lactam, >48 hours) (Liu ⊕, LC): • IV clindamycin For inpatient treatment of cellulitis in patients who are systemically ill (fever >38, tachycardia, vomiting) or have failed antibiotic therapy that covers MRSA (Liu ⊕⊕): • IV vancomycin Patients should complete 7-10 total days of antibiotic treatment. (LC, Liu ⊕). Antibiotic treatment can be extended by the PCP (Primary Care Physician) if the lesion is not completely resolved at the end of this course. • Conversion from an IV to oral antibiotic prior to discharge is not necessary (LC)

Note: Clindamycin is bacteriostatic, potential for cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA. Linezolid, daptomycin, and vancomycin have excellent efficacy in skin and soft-tissue infections against MRSA, but they should be reserved for patients who require hospitalization or have not responded to prior therapy (A-I).

62



61)







Nassisi 2012


(score 51)



(N/A)



The recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within this time period (strong, high).

For cellulitis with systemic signs of infection (moderate nonpurulent; Figure 1), systemic antibiotics are indicated. Many clinicians could include coverage against methicillin-susceptible S. aureus (MSSA) (weak, low). In a retrospective study of cellulitis and abscesses requiring hospitalization, the average duration of treatment was 2 weeks and only about one-third of patients received specific treatment for grampositive pathogens [58]. Two-thirds received very-broad-spectrum treatment, and the failure rate of 12% was not different regardless of spectrum of treatment.

• If worries about palatability or concerns about administration exist, a single oral antibiotic dose may be given prior to discharge (LC)

63



61)







Nassisi 2012


(score 51)



(N/A)



MRSA is uncommon and treatment for that organism is usually unnecessary [50]. However, coverage for MRSA may be prudent in cellulitis associated with penetrating trauma, especially from illicit drug use, purulent drainage, or with concurrent evidence of MRSA infection elsewhere. Options for treatment of MRSA in those circumstances (Table 2) include intravenous drugs (vancomycin, daptomycin, linezolid, or telavancin) or oral therapy with doxycycline, clindamycin, or SMX-TMP. If coverage for both streptococci and MRSA is desired for oral therapy, options include clindamycin alone or the combination of either SMX-TMP or doxycycline with a β-lactam (eg, penicillin, cephalexin, or amoxicillin). The activity

64



61)







Nassisi 2012


(score 51)



(N/A)



of doxycycline and SMX-TMP against β-hemolytic streptococci is not known, and in the absence of abscess, ulcer, or purulent drainage, β-lactam monotherapy is recommended. This is further substantiated by a recent double-blind study showing that a combination of SMX-TMP plus cephalexin was no more efficacious than cephalexin alone in pure cellulitis [59].

Antibiothérapie (cellulite sévère) Non-purulent (Necrotizing infection/ Cellulitis/ Erysipelas): Severe Emergent surgical inspection / debridement (rule out necrotizing process) Empiric Rx (strong, moderate) • Vancomycin (30

mg/kg/d in 2 divided doses; pediatric dose= 10–13 mg/kg/dose every 8 h IV) PLUS

For hospitalized patients with complicated SSTI (cSSTI; defined as patients with deeper soft-tissue infections, surgical/ traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns), in addition to surgical debridement and broad-spectrum antibiotics, empirical therapy for MRSA should be

∅ ∅ Severe Sepsis:

Clindamycin 900 mg IV q8h PLUS

Piperacillin/ Tazobactam 4.5 g IV q6h

(Administer Clindamycin rapidly first or at the same time)

If severe PCN allergy: Avoid Piperacillin/Tazobactam, but Meropenem is reasonable to give in severe sepsis or greater even with history of

∅ ∅

65



61)







Nassisi 2012


(score 51)



(N/A)



Piperacillin/tazobactam (3.37 g every 6–8 h IV; pediatric dose= 60–75 mg/kg/dose of the piperacillin component every 6 h IV)

OR Imipenem-cilastatin (1 g every 6–8 h IV) OR Meropenem (1 g every 8 h IV) Defined Rx (necrotizing infections) Monomicrobial • S.pyogenes ou

Clostridial sp= Penicillin (2–4 million units every 4–6 h IV; pediatric dose=60 000–100 000 units/kg/dose every 6 h IV) PLUS Clindamycin (600–900 mg every 8 h IV; pediatric dose= 10–13 mg/kg/dose every 8 h IV)

Alternative for PNC allergy= Vancomycin, linezolid, quinupristin/ dalfopristin, daptomycin • Vibrio vulnificus=

Doxycycline (100

considered pending culture data. Options include the following: • Vancomycin

(15–20 mg/kg/dose IV every 8–12 h; pediatric dose= 15 mg/kg/dose IV every 6 h) (A-I/A-II)

• Linezolid (600 mg twice daily PO/IV; pediatric dose= 10 mg/kg/dose PO/IV every 8 h, not to exceed 600 mg/dose (A-I/A-II)

• Daptomycin (4 mg/kg/dose IV once daily IV; pediatric dose= ongoing study) (A-I),

• Telavancin (10 mg/kg/dose IV once daily; pediatric dose= ND) (A-I),

• Clindamycin (600 mg IV/PO 3 times a day; pediatric dose= 10 mg/kg/dose

anaphylaxis. Consult ID (infectious diseases) if in doubt.

If MRSA confirmed or suspected: ADD Vancomycin 25 mg/kg IV load then 15 mg/kg IV q12h

Septic Shock (Pressors)/

Refractory Septic Sh.:

Source control critical. Consider STAT consults to Surgery and Infectious Disease.

Clindamycin 900 mg IV q8h PLUS

Meropenem 1g IV q8h (Administer Clindamycin rapidly first or at the same time)

If Infectious Disease opinion not readily available: ADD Vancomycin 25 mg/kg IV load, then 15 mg/kg IV q12h

In severe sepsis or septic shock, clindamycin is given rapidly first (followed by other recommended

66



61)







Nassisi 2012


(score 51)



(N/A)



mg every 12 h IV) PLUS Ceftriaxone (1 g qd IV) OR Cefotaxime (2 g tid IV)

Note: Not recommended for children but may need to use in life-threatening situations • Aeromonas

hydrophila= Doxycycline (100 mg every 12 h IV) PLUS Ciprofloxacin (400 mg every 12 h IV) OR Ceftriaxone (1 to 2 g every 24 h IV)

Note: Not recommended for children but may need to use in life-threatening situations Polymicrobial • Vancomycin (30

mg/kg/d in 2 divided doses; pediatric dose= 10–13 mg/kg/dose every 8 h IV) PLUS Piperacillin/tazobactam (3.37 g every 6–8 h IV; pediatric dose= 60–75 mg/kg/dose of the

PO/IV every 8 h, not to exceed 600 mg/dose (A-III/A-II).

In hospitalized children with cSSTI, vancomycin is recommended (A-II). If the patient is stable without ongoing bacteremia or intravascular infection, empirical therapy with clindamycin 10–13 mg/kg/dose IV every 6–8 h (to administer 40 mg/kg/day) is an option if the clindamycin resistance rate is low (eg. 10%) with transition to oral therapy if the strain is susceptible (A-II). Linezolid 600 mg PO/IV twice daily for children ≥12 years of age and 10 mg/kg/dose PO/IV every 8 h for children<12 years of age is an alternative (A-II).

therapy) to deactivate toxin production and more readily kill organisms that are in stationary phase. Unless there is an absence of source control, clindamycin as add on therapy should be given for no longer than 3 days.

67



61)







Nassisi 2012


(score 51)



(N/A)



piperacillin component every 6 h IV)

• Imipenem-cilastatin (1 g every 6–8 h IV)

• Meropenem (1 g every 8 h IV; pediatric dose= 20 mg/kg/dose every 8 h IV)

• Ertapenem (1 g daily IV; pediatric dose= 15 mg/kg/dose every 12 h IV for children 3 mo-12 y)

Alternative for PNC allergy: Cefotaxime (2 g every 6 h IV; pediatric dose= 50 mg/kg/dose every 6 h IV) PLUS metronidazole (500 mg every 6 h IV; pediatric dose= 7.5 mg/kg/dose every 6 h IV) OR clindamycin (600–900 mg every 8 h IV; pediatric dose= 10–13 mg/kg/dose every 8 h IV) Purulent (Furuncle / Carbuncle / Abscess): Note: For patients whose cellulitis is associated with:

Several antibiotics with MRSA activity are FDA- approved for the treatment of adult patients with cSSTI, such as deep soft-tissue infections, surgical and/or traumatic wound infections, major abscesses, cellulitis, infected ulcers, and burns: vancomycin, linezolid, daptomycin, tigecycline, and telavancin [50, 136–138]. Because of a recent FDA warning indicating an increased risk in all-cause mortality with tigecycline versus comparator drugs in a pooled analysis of clinical trials, the drug was not included in these guidelines, given the availability of multiple MRSA-active alternatives.

68



61)







Nassisi 2012


(score 51)



(N/A)



• penetrating trauma, • evidence of MRSA

infection elsewhere, • nasal colonization

with MRSA, • injection drug use, • purulent drainage • or SIRS (severe nonpurulent; Figure 1), vancomycin or another antimicrobial effective against both MRSA and streptococci is recommended (strong, moderate).

Severe Empiric Rx • Vancomycin (30

mg/kg/d in 2 divided doses IV; pediatric dose= 40 mg/kg/d in 4 divided doses IV) or

• Daptomycin (4 mg/kg every 24 h IV) or

• Linezolid (600 mg every 12 h IV or 600 mg bid PO; pediatric dose= 10 mg/kg every 12 h IV or PO for children <12 y) or

• Televancin or • Ceftaroline (600 mg

bid IV)

69



61)







Nassisi 2012


(score 51)



(N/A)



Notes: • Since daptomycin

and telavancin are not approved for use in children, vancomycin is recommended

• Clindamycin may be used if clindamycin resistance is < 10-15% at the institution

Defined Rx MRSA • see Empiric

MSSA • Nafcillin (1–2 g

every 4 h IV; pediatric dose= 50 mg/kg/dose every 6 h IV) or

• Cefazolin (1 g every 8 h IV; pediatric dose= 33 mg/kg/dose every 8 h IV) or

• Clindamycin (600-900 mg every 8 h IV; pediatric dose= 10–13 mg/kg/dose every 8h IV)

70



61)







Nassisi 2012


(score 51)



(N/A)



Antibiothérapie (morsures animales et humaines) For Infected Animal Bite–Related Wounds, an antimicrobial agent or agents active against both aerobic and anaerobic bacteria such as amoxicillin-clavulanate (Table 5) should be used (strong, moderate). Animal bite wounds: Based on this bacteriology: • Amoxicillin-

clavulanate (875/125 mg bid) is appropriate oral therapy that covers the most likely aerobes and anaerobes found in bite wounds.

Alternative therapies could include: • Second-generation

cephalosporins (IV or PO):

Cefuroxime (500 mg bid PO or 1 g every 12 h IV) PLUS anaerobic coverage if required: Clindamycin (300 mg

∅ PO choice: Amoxicillin/clavulanate PO alternatives: • Doxycycline (if age

>8 years and penicillin allergy)

• Clindamycin AND ciprofloxacin (for penicillin allergic patients)

IV choice: Ampicillin/sulbactam IV alternatives: Cefoxitin if penicillin allergic (transition to clindamycin AND ciprofloxacin at discharge) Call ID for other scenarios

∅

Human or animal Bites: Amox/Clav 500/125 mg PO TID

∅ Dumaresq 2016, CISSS Chaudière-Appalaches : La cloxacilline, les céphalosporines de 1ère génération (céphalexine, céfadroxil, céfazoline) et la clindamycine ne sont pas recommandés pour le traitement d’une infection cutanée post morsure féline, canine ou humaine. Le premier choix est la combinaison amoxicilline-clavulanate (7 à 10 jours pour le traitement), avec comme principale alternative la combinaison de doxycycline et métronidazole. Pour les infections modérées nécessitant un traitement initial parentéral, la ceftriaxone est

71



61)







Nassisi 2012


(score 51)



(N/A)



tid PO or 600 mg every 6–8 h IV) OR Metronidazole (250–500 mg tid PO or 500 mg every 8 h IV) • Other second- or

third-generation cephalosporins:

Cefoxitin (1 g every 6–8 h IV) Ceftriaxone (1 g every 12 h IV) Cefotaxime (1–2 g every 6–8 h IV) PLUS anaerobic coverage if required: Clindamycin (300 mg tid PO or 600 mg every 6–8 h IV) OR Metronidazole (250–500 mg tid PO or 500 mg every 8 h IV) • A carbapenem:

Ertapenem (1 g daily IV; pediatric dose= 15 mg/kg/dose every 12 h IV for children 3 mo-12 y) OR Meropenem (1 g every 8 h IV; pediatric dose= 20 mg/kg/dose every 8 h IV) OR Imipenem-cilastatin (1 g every 6–8 h IV) • Moxifloxacin (400

mg daily PO/IV) • Doxycycline (100

recommandée, ± métronidazole. Pour les infections plus sévères, la combinaison pipéracilline-tazobactam ou le méropénem sont recommandés.

72



61)







Nassisi 2012


(score 51)



(N/A)



mg bid PO or 100 mg every 12 h IV)

• SMX-TMP (160–800 mg bid PO or 5–10 mg/kg/day of TMP component IV) PLUS anaerobic coverage

• Ciprofloxacin (500–750 mg bid PO or 400 mg every 12 h IV) PLUS anaerobic coverage

• Levofloxacin (750 mg daily PO/IV) PLUS anaerobic coverage

Unless no alternative agents are available, macrolides should be avoided due to variable activity against Pasteurella multocida and fusobacteria. Pregnancy is a relative contraindication for use of tetracyclines and fluoroquinolones, whereas SMX-TMP may be safely prescribed except in the third trimester of pregnancy [140, 141, 143, 156–160].

73



61)







Nassisi 2012


(score 51)



(N/A)



Human bite wounds: Eikenella corrodens is resistant to first-generation cephalosporins, macrolides, clindamycin, and aminoglycosides (Table 5). Therefore, treatment is recommended with: • Amoxicillin-

clavulanate (875/125 mg bid PO)

• Ampicillin-sulbactam (1.5–3.0 g every 6 h IV)

• Ertapenem (1 g daily IV; pediatric dose= 15 mg/kg/dose every 12 h IV for children 3 mo-12 y)

• Meropenem (1 g every 8 h IV; pediatric dose= 20 mg/kg/dose every 8 h IV)

• Imipenem-cilastatin (1 g every 6–8 h IV)

If there is history of hypersensitivity to β-lactams: • Ciprofloxacin (500–

750 mg bid PO or

74



61)







Nassisi 2012


(score 51)



(N/A)



400 mg every 12 h IV) PLUS anaerobic coverage

• Levofloxacin (750 mg daily PO/IV) PLUS anaerobic coverage

• Moxifloxacin (400 mg daily PO/IV)

Cultures are often not done on wounds, and empirical therapy might miss pathogens. The bacteriology of these wounds can differentiate the number of isolates per wound and whether additional coverage for anaerobes is required.

Antibiothérapie (cellulite faciale d’origine dentaire) ∅ ∅ IV choice: Penicillin

OR Ampicillin/sulbactam IV alternatives: Clindamycin if penicillin allergic PO choice: Penicillin OR Amoxicillin/clavulanate PO alternatives: Clindamycin if penicillin allergic

∅ ∅ ∅ ∅

Antibiothérapie (cellulite périorbitaire ou orbitaire)

75



61)







Nassisi 2012


(score 51)



(N/A)



∅ ∅ ∅ ∅ ∅ Wald 2013: Complications of Acute Bacterial Sinusitis: Orbital complications have been classified by Chandler et al.32 Periorbital and intraorbital inflammation and infection are the most common complications of acute sinusitis and most often are secondary to acute ethmoiditis in otherwise healthy young children. These disorders are commonly classified in relation to the orbital septum; periorbital or preseptal inflammation involves only the eyelid, whereas postseptal (intraorbital) inflammation involves structures of the orbit. Mild cases of preseptal cellulitis (eyelid <50% closed) may be treated on an outpatient basis with appropriate oral

∅

76



61)







Nassisi 2012


(score 51)



(N/A)



antibiotic therapy (high-dose amoxicillin-clavulanate for comprehensive coverage) for acute bacterial sinusitis and daily follow-up until definite improvement is noted. If the patient does not improve within 24 to 48 hours or if the infection is progressive, it is appropriate to admit the patient to the hospital for antimicrobial therapy. Similarly, if proptosis, impaired visual acuity, or impaired and/or painful extraocular mobility is present on examination, the patient should be hospitalized, and a contrast-enhanced CT should be performed. Consultation with an otolaryngologist, an ophthalmologist, and an infectious disease expert is appropriate for guidance regarding the need for surgical

77



61)







Nassisi 2012


(score 51)



(N/A)



intervention and the selection of antimicrobial agents. High dose amoxicillin-clavulanate = 80–90 mg/kg per day of the amoxicillin component with 6.4 mg/kg per day of clavulanate in 2 divided doses with a maximum of 2 g per dose.

Antibiothérapie (infection de plaies chirurgicales) Adjunctive systemic antimicrobial therapy is not routinely indicated, but in conjunction with incision and drainage may be beneficial for surgical site infections associated with a significant systemic response (Figure 2) such as erythema and induration extending >5 cm from the wound edge, temperature >38.5°C, heart rate >110 beats/minute, or white blood cell (WBC) count >12 000/μL (weak, low). Patients with temperature >38.5°C or heart rate >110 beats/ minute or erythema

For hospitalized patients with complicated SSTI (cSSTI; defined as patients with deeper soft-tissue infections, surgical/ traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns), in addition to surgical debridement and broad-spectrum antibiotics, empirical therapy for MRSA should be considered pending culture data. Options include the following: • Vancomycin

∅ ∅ ∅ ∅ ∅

78



61)







Nassisi 2012


(score 51)



(N/A)



extending beyond the wound margins for >5 cm may require a short course (eg, 24–48 hours) of antibiotics, as well as opening of the suture line (Figure 2). The antibiotic choice is usually empiric but can be supported by Gram stain, culture of the wound contents (Table 2), and the site of surgery. A brief course of systemic antimicrobial therapy is indicated in patients with surgical site infections following clean operations on the trunk, head and neck, or extremities that also have systemic signs of infection (strong, low): • First-generation

cephalosporin (Cefazolin 0.5–1 g every 8 h IV OR Cephalexin 500 mg every 6 h PO)

• Antistaphylococcal penicillin for MSSA (Oxacillin or Nafcillin 2 g every 6 h IV)

(15–20 mg/kg/dose IV every 8–12 h; pediatric dose= 15 mg/kg/dose IV every 6 h) (A-I/A-II)

• Linezolid (600 mg twice daily PO/IV; pediatric dose= 10 mg/kg/dose PO/IV every 8 h, not to exceed 600 mg/dose (A-I/A-II)

• Daptomycin (4 mg/kg/dose IV once daily IV; pediatric dose= ongoing study) (A-I),

• Telavancin (10 mg/kg/dose IV once daily; pediatric dose= ND) (A-I),

• Clindamycin (600 mg IV/PO 3 times a day; pediatric dose= 10 mg/kg/dose PO/IV every 8 h, not to exceed 600 mg/dose (A-III/A-II).

79



61)







Nassisi 2012


(score 51)



(N/A)



Where risk factors for MRSA are high (nasal colonization, prior MRSA infection, recent hospitalization, recent antibiotics): • Vancomycin (15

mg/kg every 12 h IV)

• Linezolid (600 mg every 12 h IV OR 600 mg bid PO; pediatric dose= 10 mg/kg every 12 h IV or PO for children <12 y)

• Daptomycin (4 mg/kg every 24 h IV)

• Telavancin • Ceftaroline

(strong, low) For infections following operations on the axilla, gastrointestinal (GI) tract, perineum, or female genital tract (Table 2), agents active against gram-negative bacteria and anaerobes are recommended (strong, low): • Metronidazole (500

mg every 8 h IV) PLUS Ceftriaxone (1 g every

In hospitalized children with cSSTI, vancomycin (15 mg/kg/dose IV every 6 h) is recommended (A-II). If the patient is stable without ongoing bacteremia or intravascular infection, empirical therapy with clindamycin (10–13 mg/kg/dose IV every 6–8 h to administer 40 mg/kg/day) is an option if the clindamycin resistance rate is low (eg. 10%) with transition to oral therapy if the strain is susceptible (A-II). Linezolid (600 mg PO/IV twice daily for children ≥12 years of age and 10 mg/kg/dose PO/IV every 8 h for children<12 years of age) is an alternative (A-II).

80



61)







Nassisi 2012


(score 51)



(N/A)



24 h IV) OR Ciprofloxacin (400 mg IV every 12 h or 750 mg PO every 12 h) OR Levofloxacin (750 mg IV every 24 h)

Antibiothérapie (autres cas particuliers) Severe infection: • Vibrio vulnificus=

Doxycycline (100 mg every 12 h IV) PLUS Ceftriaxone (1 g qd IV) OR Cefotaxime (2 g tid IV)

Note: Not recommended for children but may need to use in life-threatening situations • Aeromonas

hydrophila= Doxycycline (100 mg every 12 h IV) PLUS Ciprofloxacin (400 mg every 12 h IV) OR Ceftriaxone (1 to 2 g every 24 h IV)

Note: Not recommended for children but may need to use in life-threatening situations

∅ If fresh or saltwater contact, or other special circumstance, discuss with ID

∅ Salt water:

Doxycycline 200 mg PO x 1 then 100 mg PO BID

Fresh water:

Ciprofloxacin 500 mg PO BID

∅ ∅

81



61)







Nassisi 2012


(score 51)



(N/A)



In severely compromised patients as defined in question 13 [patients with malignancy on chemotherapy, neutropenia, severe cell-mediated immunodeficiency, immersion injuries, and animal bites] (severe nonpurulent; Figure 1), broad-spectrum antimicrobial coverage may be considered (weak, moderate). Vancomycin plus either piperacillin-tazobactam or imipenem/meropenem is recommended as a reasonable empiric regimen for severe infections (strong, moderate). For patients with febrile neutropenia who present with skin and soft tissue lesions: hospitalization and empiric antibacterial therapy with vancomycin plus antipseudomonal antibiotics such as cefepime, a

82



61)







Nassisi 2012


(score 51)



(N/A)



carbapenem (imipenem-cilastatin or meropenem or doripenem), or piperacillin-tazobactam are recommended (strong, high); Documented clinical and microbiologic SSTIs should be treated based on antimicrobial susceptibilities of isolated organisms (strong, high); It is recommended that the duration of treatment for most bacterial SSTIs should be for 7–14 days (strong, moderate). The appropriate antibiotics for patients with suspected or confirmed SSTI (initial infection) should be broad-spectrum agents administered at the first clinical signs or symptoms of infection [203].No single empiric regimen is superior, but all recommended regimens should meet the following criteria (Table 7):

83



61)







Nassisi 2012


(score 51)



(N/A)



• broad-spectrum antimicrobial activity including P. aeruginosa,

• bactericidal in the absence of circulating neutrophils,

• low antibiotic-associated toxicity.

For patients in whom vancomycin may not be an option, daptomycin, ceftaroline, or linezolid should be added to the initial empiric regimen. Linezolid, daptomycin, or ceftaroline have activity against MRSA [204] and have received FDA approval for the treatment of SSTIs, but have not been comprehensively studied in patients with neutropenia. The use of linezolid in this patient population has been associated with delayed ANC recovery [205, 206]. The combination of ciprofloxacin and amoxicillin-clavulanate is the preferred oral antibiotic regimen for low-risk patients [207,

84



61)







Nassisi 2012


(score 51)



(N/A)



208]. Levofloxacin has better gram-positive activity than ciprofloxacin, but is less potent than ciprofloxacin against P. aeruginosa, causing some to suggest that a higher dose of levofloxacin therapy (750 mg daily) may be required.

Suivi In some patients, cutaneous inflammation and systemic features worsen after initiating therapy, probably because sudden destruction of the pathogens releases potent enzymes that increase local inflammation [58].

∅ All patients who have had an I&D procedure should have reliable follow-up for re-evaluation with their PCP in 24 - 48 hours. For outpatient treatment, Primary Medical Doctor follow-up within 24h-48h. A patient is ready for discharge when: • Lesion(s) show signs of improvement • Tolerating PO • Pain well controlled • No fever > 24 hours • Follow up assured within 48 hours (LC)

∅ Redness and edema increase for 1-2 days after appropriate antibiotic use due to toxin release (yet pain, systemic symptoms, if present, will have improved).

∅ Dumaresq 2016, CISSS Chaudière-

Appalaches :

La cellulite peut prendre jusqu’à 3 jours (72 heures)

avant de s’améliorer. Il y a parfois même une détérioration

transitoire des signes

inflammatoires cutanés dans les premières 24 à 48 heures malgré un

traitement adéquat, probablement en raison de la lyse

bactérienne survenant

rapidement après le début du traitement.

Dans ces cas,

85



61)







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malgré une augmentation de la

rougeur, les patients décrivent

habituellement une diminution de la

douleur, une disparition des frissons le cas

échéant, et une amélioration de l’état

général.

Pour plusieurs cellulites, il faut s’attendre à une

dermite inflammatoire

résiduelle prenant parfois quelques

semaines à disparaître. Il est

donc très important d’en informer les patients puisqu’il

s’agit d’une raison fréquente pour

laquelle les patients consultent à

nouveau. Orientation en milieu spécialisé

SSTIs in Patients With Cellular Immunodeficiency : Consider immediate consultation with a

∅ Specific locations of cellulitis/abscess warrant subspecialist consultation to evaluate for deeper and more

∅ ∅ Desrosiers 2011: Urgent consultation should be obtained for acute sinusitis with unusually severe symptoms or systemic

∅

86



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dermatologist familiar with cutaneous manifestations of infection in patients with cellular immune defects (eg, those with lymphoma, lymphocytic leukemia, recipients of organ transplants, or receiving immunosuppressive drugs such as anti–tumor necrosis factor (TNF) or certain monoclonal antibodies) (weak, low).

Compléments d’information tirés du GPC IDSA 2005:

An expert in hand care should evaluate clenched-fist injuries for penetration into the synovium, joint capsule, and the bone (B-III).

serious/complicated extension of infection. • Orthopedics: Infections over joints, infections of hand/fingers/feet • General surgery: Peri-anal abscess (within 1 cm of anal verge), pilonidal abscess, perineal abscess, breast abscess • ENT: Neck abscess • Dental: Facial cellulitis of dental origin (LC) Note: Also consult General Surgery if an inpatient develops any abscess requiring drainage (LC) Prior to consulting Orthopedics, obtain the following: • Blood work: Complete blood count with differential, C-reactive protein, and erythrocyte sedimentation rate. Consider blood culture for ill-appearing or febrile patients. • Radiographs: Obtain appropriate films of

toxicity or where orbital or intracranial involvement is suspected. (Option, Strong) Extension of disease beyond the confines of the sinuses is a medical emergency and requires aggressive assessment, medical therapy, and potential surgical drainage. Individuals with suspected complications should be urgently referred to a setting with appropriate imaging facilities and qualified specialty care. Because of the serious nature of complications, patients with suspected complications of ABRS should be immediately referred to an otolaryngologist with appropriate consultation from other services, including (but not limited to) ophthalmology, neurosurgery, and infectious diseases.

87



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the affected area; typically more than one view is required (LC)

Outil de gradation de la preuve utilisé dans les GPC sélectionnés Strong recommendation, high-quality evidence: Desirable effects clearly outweigh undesirable effects or vice versa; Consistent evidence from well performed RCTs or exceptionally strong evidence from unbiased observational studies. Strong recommendation, moderate quality evidence: Desirable effects clearly outweigh undesirable effects or vice versa; Evidence from RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from unbiased observational studies. Strong recommendation, low-quality quality evidence: Desirable effects clearly

Strength of recommendation: A = Good evidence to support a recommendation for or against use. B = Moderate evidence to support a recommendation for or against use. C = Poor evidence to support a recommendation. Quality of evidence I = Evidence from ≥1 properly randomized, controlled trial. II = Evidence from ≥1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from >1 center); from multiple time-series; or from dramatic results from uncontrolled experiments.

We used the GRADE method of rating evidence quality. Evidence is first assessed as to whether it is from randomized trial, or observational studies. The rating is then adjusted in the following manner: Quality ratings are downgraded if studies: • Have serious limitations • Have inconsistent results • If evidence does not directly address clinical questions • If estimates are imprecise OR • If it is felt that there is substantial publication bias

Quality ratings can be upgraded if it is felt that: • The effect size is large • If studies are

Strength of Recommendation: A= Good evidence to support a recommendation for use B= Moderate evidence to support a recommendation for use C= Poor evidence to support a recommendation D= Moderate evidence to support a recommendation against use E= Good evidence to support a recommendation against use

Quality of Evidence: I= Evidence from ≥ 1 properly randomized controlled trial II= Evidence from ≥ 1 well-designed clinical trial, without randomization; from

∅ ∅ ∅

88



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outweigh undesirable effects or vice versa; Evidence for at least 1 critical outcome from observational studies, RCTs with serious flaws or indirect evidence. Strong recommendation, very low-quality evidence (very rarely applicable): Desirable effects clearly outweigh undesirable effectsor vice versa; Evidence for at least 1 critical outcome from unsystematic clinical observations or very indirect evidence. Weak recommendation, high-quality evidence: Desirable effects closely balanced with undesirable effects; Consistent evidence from well performed RCTs or exceptionally strong evidence from unbiased observational studies. Weak recommendation, moderate-quality evidence: Desirable effects closely balanced with undesirable effects;

III = Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

designed in a way that confounding would likely underreport the magnitude of the effect OR • If a dose-response gradient is evident

Quality of Evidence: ⊕⊕⊕⊕ High quality ⊕⊕⊕ Moderate quality ⊕⊕ Low quality ⊕ Very low quality (E) Expert Opinion (LC) Local Consensus Reference: Guyatt G et al. J Clin Epidemiol 2011;64(4):383-94

cohort or case-controlled analytic studies (preferably from > 1 center); from multiple time-series; or from dramatic results of uncontrolled experiments III= Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

89



61)







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(score 51)



(N/A)



Evidence from RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from unbiased observational studies. Weak recommendation, low-quality evidence: Uncertainty in the estimates ofdesirable effects, harms, and burden; desirable effects, harms, and burden may be closely balanced; Evidence for at least 1 critical outcome from observational studies, from RCTs with serious flaws or indirect evidence. Weak recommendation, very low-quality evidence: Major uncertainty in the estimates of desirable effects, harms, and burden; desirable effects may or may not be balanced with undesirable effects; Evidence for at least 1 critical outcome from unsystematic clinical

90



61)







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(score 51)



(N/A)



observations or very indirect evidence.

91

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Cellulite infectieuse chez l’adulte et l’enfant · Ce guide traite du diagnostic et du...

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