Les péritonites
Antoine Dewitte SAR 2
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
Définition
¡ Réaction inflammatoire de tout ou partie du péritoine, d’origine infectieuse ou non
¡ Classification / Mode de contamination péritonéale
l Péritonites primaires ou primitives
¡ Péritonite spontanée (cirrhose) ¡ Péritonite granulomateuse (Mycobacterium
sp, Histoplasma sp, Strongiloides sp) ¡ Péritonite périodique, péritonite primaire
(Pneumococcus sp ou Streptococcus sp)
Modified Hamburg Ethiopathogenic Classification 1987
Définition ¡ Péritonites secondaires
l Perforation d’un viscère intra-abdominal ¡ Spontanée ¡ Péritonites postopératoires, postendoscopiques ¡ Post-traumatique (plaie pénétrante ou
contusion) ¡ Nécrose de la paroi intestinale
l Infection aiguë d’un viscère intra-abdominal ou pelvien
l Dialyse péritonéale continue ambulatoire
¡ Péritonites tertiaires : habituellement péritonites déjà opérées avec contrôle inefficace de la source
Wittmann Ann Surg 1996
Classification ¡ Péritonites communautaires : survenue en
milieu non hospitalier
¡ Péritonites nosocomiales:
l Péritonites postopératoires (PPO)
l Péritonites tertiaires: ¡ Reprises chirurgicales multiples ¡ Tableau de défaillance multiviscérale ¡ Peu ou pas de liquide péritonéal ¡ Pas de germes ou germes réputés peu pathogènes
(entérocoques, levures, staphylocoques coagulase négative, entérobactéries)
Solomkin J et al. Clin Infect Dis 2003;37:997-1005
Définition Ce qui n’est pas une péritonite: ¡ Contamination/infection intra-abdominale
l Contamination limitée dans le temps par lésions du tube digestif traumatique ou per-opératoire ou encore par endoscopie et opéré dans les 12 heures
l Perforation gastro-duodénale opérée dans les 24 heures
¡ Foyer infecté ou inflammatoire éradiqué par la chirurgie l Appendicite aiguë ou gangréneuse l Cholécystite aiguë ou gangréneuse l Nécrose intestinale (d’origine vasculaire ou volvulus) sans
perforation
1 – « Antibioprophylaxie » pas tout à fait dans le cadre habituel =>24h d’antibiothérapie maximum
2 – Bien évaluer les lésions en se basant sur la description chirurgicale
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
Lésion sus-mésocolique
¡ Estomac l Ulcère l Néoplasie
¡ Duodénum l Ulcère
¡ Voies biliaires l Perforation
vésiculaire
Lésion sous-mésocolique
¡ Colon l Appendicite
perforée l Néoplasie l Diverticulite l Traumatisme l Infection (Colites,
Amibiase…) l RCH
¡ Rectum l RCH l Traumatisme l Cancer
¡ Jéjunum - Iléon l Diverticule de Meckel l Maladie de Crohn l Traumatique l Ischémique
¡ Occlusion/bride ¡ Infarctus ¡ Invagination
* Résultats groupés pour les infections communautaires et postopératoires
Péritonites communautaires Dupont Lepape Roehrborn Sotto*
Infection communautaire 115 761 68 82
Localisation sus-mésocolique 32 (28) 195
(26) 24 (35) 33 (40)
Voies biliaires 7 103 5 10 Estomac ou duodénum 25 92 19 23
Localisation sous-mésocolique 81 (70) 566
(74) 44 (68) 71 (87)
Appendicite 18 374 20 14 Intestin grêle 21 51 4 9 Côlon 42 140 20 48 Divers 2 (2) 1 - 16
Etiologies des péritonites post-opératoires
Guivarch Roehrborn (Ann Chir 1977) (Clin Infect Dis 2001)
¡ Lâchage de suture ou d’anastomose 72 % 66 %
¡ Perforation 9 % 10 %
¡ Abcès 4 % 13 %
¡ Autres 15 % 10 %
Lésion initiale des péritonites post-opératoires
¡ Dellinger (Arch Surg 1985) l Colique 34 % l Sus mésocolique 19 % l Intestin grêle 15 % l Appendice 4 % l Autres 29 %
¡ Roehrborn (Clin Infect Dis 2001) l Colique 40 % l Sus mésocolique 21 % l Pancréas 15 % l Intestin grêle 13 % l Appendice 4 % l Autres 6 %
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
Péritoine normal
¡ Surface environ 2 m² chez l ’adulte
¡ Echanges bidirectionnels avec la circulation générale (au travers de la séreuse = membrane semiperméable)
¡ Echanges avec la circulation lymphatique = voie d ’épuration l favorisés par les mouvements respiratoires
¡ vers les lymphatiques diaphragmatiques ¡ puis vers le canal thoracique
Moyens de défense ¡ Drainage lymphatique
l limite les concentrations bactériennes péritonéales
¡ Mouvements diaphragmatique l migration des épanchements vers les régions sous
phréniques
¡ Gravité l localisation dans les zones déclives pelvis et
paracoliques
¡ Epiploon l limitation du processus infectieux l colmatage d’une brêche ou d’une région
inflammatoire l adhérences et exsudats fibrineux
Facteurs aggravants
Andersson, Acta Chir Scand 1989
Riché FC, Critical Care 2009; 13: R99
Facteurs aggravants Survival according to biliary or non-biliary origin of
peritonitis with shock (%)
Mortalité
⇒ Mortalité du choc septique = 40-60%
Annane D et al Current epidemiology of septic shock: the CUB-Réa Network.. Am J Respir Crit Care Med. 2003 15;168:165-72.
⇒ Mortalité des péritonites = 45-90%
-sepsis sévère?
-défaillance d’organe?
Rau BM et al Evaluation of procalcitonin for predicting septic multiorgan failure and overall prognosis in secondary peritonitis: a prospective, international multicenter study.
Arch Surg 2007;142:134-42
⇒ Gravité corrélée au nombre de défaillance d’organe (score SOFA+++)
Paugam-Burtz C et al. Daily organ-system failure for diagnosis of persistent intraabdominal sepsis after post-operative peritonitis. Intensive Care Med 2002;28:594-8
Facteurs associés à la mortalité: l âge>60 ans l APACHE II>15-20 l Chirurgie retardée l Index de
Mannheim >26
Facteurs aggravants
Notash A et al Evaluation of Mannheim peritonitis index and multiple organ failure score in patients with peritonitis. Indian J Gastroenterol 2005; 24:197-200
Physiopathologie : Péritonite localisée
¡ Phase initiale (processus inflammatoire localisé < 105 bactéries /ml): l Augmentation perméabilité péritonéale
¡ Épanchement liquidien intra-péritonéal (plasma riche en anticorps et en fibrine) l Division de la cavité péritonéale en espaces
anatomiques différents
¡ Accumulation intrapéritonéale granulocytes et monocytes (12 à 24 h):
c Phagocytose bactérienne l Guérison complète l Ou évolution vers abcès
Modèle de perforation coecale expérimentale
bactéries
phagocytes
Péritoine vu en microscopie à balayage Vue une heure après la perforation
Modèle de perforation coecale expérimentale
bactéries phagocytes
12h plus tard…
Épanchements liquidien intra-péritonéaux
Sous phrénique
Sous hépatique
Épanchements liquidien intra-péritonéaux
Entre les anses grêles
Épanchements liquidien intra-péritonéaux
Inter mésentérique
Gouttières pariétocoliques
Physiopathologie : Péritonite généralisée
¡ Diffusion rapide du processus inflammatoire l Micro-organisme particulièrement virulent l Concentration élevée de micro-organismes l Défaillance du système immunitaire
¡ Péritonite bactérienne : Pathogénie principalement liée à endotoxine (gram négatif)
Physiopathologie : Péritonite généralisée ¡ Effets pathogènes complexes:
l Niveau systémique ¡ Centre thermorégulateur : hyperthermie ¡ Granulopoïèse et cellules phagocytaires:
leucopénie puis leucocytose l Système vasculaire
¡ Rétention liquidienne et constitution d’un 3ème secteur : insuffisance rénale, insuffisance respiratoire (inflammation, translocation)
¡ Activation des systèmes biologiques du complément ou de la coagulation
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
Infection polymicrobienne
Infection polymicrobienne
Montravers et al. JAC 2009
Bactéries contaminantes
Germes et Mortalité
Onderdonk Infect Immun 1976
Bactéries contaminantes
Riché FC, Critical Care 2009; 13: R99
Septic shock n = 42 ; no septic shock n = 70
Bactéries contaminantes
Montravers et al. JAC 2009
Groupe 3
¡ Enterobacter sp Citrobacter freundii Serratia marcescens
Profils de résistance des BGN
Montravers et al, Clinical and microbiological profiles of community-acquired and nosocomial intra-abdominal infections: results of the French prospective,
observational EBIIA study. JAC 2009
Emergence des entérobactéries BLSE dans les infections communautaires
¡ E coli : émergence de souches plus résistantes l En communautaire : CTX-M
¡ non prévisible (infections urinaires de ville traitée par Bactrim ?)
¡ Actifs : carbapénèmes l En hospitalier : tout = BLSE et hypercase
¡ Métallo-BLSE : Klebsiella entre autres l Résistant à tout ou presque l Grecs et turcs (mauvaise utilisation des
antibiotiques facteur majeur)
Emergence des entérobactéries BLSE dans les infections communautaires
¡ Autant en ville qu’à l’hôpital
¡ Sont en partie responsables d’une augmentation de consommation des Carbapénèmes (a doublé en 10 ans)
¡ Emergence des carbapénémases : > 1 % en France vs 25% en Italie ou 25 à 50% en Grèce
¡ Une réflexion sur l’importance de trouver une alternative aux carbapénèmes.
Emergence des entérobactéries BLSE dans les infections communautaires
¡ Les ß-lactamines agissent sur la synthèse du peptidoglycane en inhibant les protéines liant la pénicilline (PLP) par formation d’un complexe covalent rendant l’enzyme inactive (carboxypeptidase, transglycosidase et transpeptidase)
=>modification du peptidoglycane =>la paroi bactérienne fragilisée =>lyse bactérienne
ENTEROCOQUES ET ß-LACTAMINES
ENTEROCOQUES ET ß-LACTAMINES
¡ Résistance naturelle: PLP5 naturelle de faible affinité pour Péni-G ⇒ RHN aux céphalosporines à l’oxacilline, aux
monobactames ⇒ sensibilité diminuée aux pénicillines
¡ Résistance acquise: l fréquente chez E. faecium(hyperproduction de
PLP5) l croisée entre toutes les pénicillines l USA : VRE
ENTEROCOQUES ET ß-LACTAMINES
¡ En France: l E.faecium(n=134) : 70.1 % ampicilline résistant l E.faecalis(n=356) : 98.6 % ampicilline sensible
¡ En Angleterre: l E.faecium(n=56) : 96,4 % ampicilline résistant l E.faecalis(n=166) : 100% ampicilline sensible
souches hospitalières 1999-2000 : C.J.Soussy et coll.
A.P Johnson et al 2003
Profil de résistances des Entérocoques
Montravers et al. JAC 2009
Profils de résistance des anaérobies
Montravers et al. JAC 2009
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic
l Péritonites communautaires ¡ Prise en charge
Douleur spontanée Localisée dans la phase initiale et diffuse par la suite
Tonus musculaire abdominal Défense ou contracture
Péristaltisme Diminué ou disparu
Température corporelle Hyperthermie (> 38,5°C)
Respiration Tachypnée et hyperventilation
Pression sanguine Normale dans la phase initiale, puis chute de la pression systolique
Diurèse Diminuée (< 30 ml/h)
Toucher rectal ? Proske JM, La Revue du Praticien 2005; 55: 2167-2172
Diagnostic clinique
¡ La contracture abdominale affirme le diagnostic
¡ Doute présence contracture : valeur ajoutée des investigations complémentaires
Investigations complémentaires
Radiographie de l’abdomen sans préparation (ASP)
Pneumopéritoine bilatéral
Scanner abdominal
Pneumopéritoine et collection liquidienne abdominale
Explorations radiologiques
Explorations radiologiques
¡ Localisation des douleurs l Oriente vers la pathologie initiale en cause l Formes trompeuses (péritonite appendiculaire)
=> Echographie abdominale?
¡ Scanner abdominal l Grande valeur dans diagnostic étiologique des
appendicites, sigmoïdites et autres pathologies inflammatoires du tube digestif
l Moins performant dans recherche des causes d’une perforation digestive
l Essentiel dans prise en charge des péritonites tertiaires et diagnostic de péritonite postopératoire
¡ Hémocultures aéro-anaérobies + fongiques ¡ Culture liquide péritonéal (Candida) et étude de
sensibilité aux AB pour les espèces prédominantes ¡ Culture des liquides de drainage inutile en cours
d’évolution sauf aggravation secondaire
Apport de la microbiologie Recommandations
Ann Fr Anesth Réanim 2001;20:suppl 2; 350-367
• Intérêt individuel: -Péritonites communautaires : discutable, en pratique fait en France -Péritonites nosocomiales: Intérêt individuel indiscutable
• Justificatif au plan collectif : surveillance de l’évolution des résistances des bactéries communautaires responsables d’infections graves
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic
l Péritonites communautaires l Infections post-opératoires
¡ Prise en charge
Infections post-opératoires
Date de survenue : -5-8ème jour postopératoire -après 2 ème semaine
Hopkins Am Surg 1993
Diagnostic clinique Signes cliniques (%) Guivarch Ann
Chir (1977) Hinsdale
Ann Surg (1984)
Levy Ann Chir (1985)
Fièvre 86 86 83
Douleurs abdominales 79 90 44
Aspiration gastrique productive
32 - 33
Iléus 45 85 13
Diarrhées 26 - 41
Ballonnement - 15 42
Issue de pus ou de lq digestif
48 10 33
Masse palpable - 2 10
Fréquence des défaillances viscérales au cours des péritonites postopératoires
Critères de réintervention
Formels Surveillance renforcée
Défaillance viscérale Hyperleucocytose croissante
Pus ou liquide dans les drains
Fièvre isolée inexpliquée
Signes locaux cliniques Signes radiologiques
Troubles du transit isolés
Fort doute diagnostic Signes biologiques de défaillance
Dazza FE, 1985, réanimation et médecine d’urgence
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
l Traitement chirurgical
Principes du traitement chirurgical
¡ Identifier la source de contamination
¡ Supprimer la source de contamination
¡ Identifier les germes en cause ¡ Réduire l’inoculum bactérienne ¡ Prévenir la récidive ou la
persistance de l'infection
Importance du geste chirurgical
¡ Mortalité l TTT chirurgical correct + AB adaptée: 6 % l TTT chirurgical incorrect + AB adaptée: 90 %
¡ Contrôle de la source infectieuse:
l Contrôle chirurgical impossible: 27% de décès l Contrôle possible: 13% décès
Seiler C et al. Surgery 2000;127:178-84
Seiler C et al. Surgery 2000;127:178-84
Qualité de l’opérateur
¡ Incidence des infections postopératoires variable selon le degré de qualification de l’opérateur
¡ Risque X par 8,4 en cas d’opérateur junior
¡ Réduction des complications à mesure de la formation
¡ Risque d’infection postopératoire de X 0,5
à X 2 selon l’opérateur
Haouet K, et al. La Tunisie Médicale. 2000;78:634-40.
Lau WY, et al. Am J Surg. 1988;155:322-6.
Bremmelgaard A, et al. J Hosp Infect. 1989;13:1-18
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
l Traitement chirurgical l Traitement antibiotique
Objectifs de l’antibiothérapie probabiliste
¡ 1 - Spectre Adapté
¡ 2 - Posologie Adaptée
Impact d’un traitement initial inadapté
Montravers Clin Infect Dis 1996
100 péritonites postopératoires
Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.
Clin Infect Dis. 2010 Jan 15;50(2):133-64
IDSA Guidelines
Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.
Clin Infect Dis. 2010 Jan 15;50(2):133-64
IDSA Guidelines
Recommandations classiques
¡ Péritonite communautaire : l C3G +metronidazole pour l’instant
¡ Péritonites nosocomiales : l germes hospitaliers résistants
¡ Pour l’instant pas de prise en compte du Coli BLSE communautaire, sauf si choc septique
¡ FDR de BMR
Péritonites post-opératoires
Augustin P et al, Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis;Crit Care. 2010;14(1):R20. Epub 2010 Feb 15.
Péritonites post-opératoires
Augustin P et al, Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis;Crit Care. 2010;14(1):R20. Epub 2010 Feb 15.
Péritonites post-opératoires
Augustin P et al, Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis;Crit Care. 2010;14(1):R20. Epub 2010 Feb 15.
Antibiothérapie des PPO
¡ Adaptée à l’écologie locale ¡ Différente de l’antibiothérapie
précédente ¡ Prenant en compte tous les germes ¡ Intégrée dans une réflexion
pluridisciplinaire
Faut-il prendre en compte la gravité du tableau?
% d’échec selon la gravité et le type de traitement
Solomkin JS. Ann Surg 1990 ; 212:581-91
Intérêt des aminosides?
¡ Infections sévères ¡ Infections récurrentes/reprises
chirurgicales itératives ¡ Persistance en fin d'intervention
d'un inoculum élevé ¡ Risque de présence de BMR
l antibiothérapie dans les 30 jours l hospitalisations multiples/prolongées
¡ Risque d’émergence de résistance
Gorbach J Antmicrob Chemother 1993
Intérêt des aminosides?
Dupont H et al. Antimicrob Agents Chemother. 2000;44:2028-2033.
Comparaison monothérapie / bithérapie
Durée de traitement
¡ Option 1 : durée fixe (globalement durée en diminution) l 5 à 7 jours (probablement plutôt 5 j) l notion de réduction de l ’inoculum par
l’acte chirurgical l péritonites limitées: pour certains 48h
suffisent
Durée de traitement ¡ Option 2 : se guider sur l ’évolution
clinique l arrêt du traitement quand le malade est
apyrétique et a un compte de GB normal ¡ aussi efficace que durée fixe ¡ durée d ’antibiothérapie en moyenne plus
courte l mais prolongation si patient reste fébrile :
¡ en principe plutôt du à un foyer infectieux persistant
¡ pas d ’étude démontrant l ’intérêt d ’une antibiothérapie prolongée
¡ Cas à part : péritonites tertiaires : antibiothérapie peu efficace
Durée de traitement
Bouadma L et al; Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial, Lancet. 2010 Feb 6;375(9713):463-74
Durée de l’antibiothérapie
Bouadma L et al; Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial, Lancet. 2010 Feb 6;375(9713):463-74
Durée de l’antibiothérapie
Survie à J28 et J60
Bouadma L et al; Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial, Lancet. 2010 Feb 6;375(9713):463-74
Durée de l’antibiothérapie
Essai PRORATA: in press Bouadma L et al; Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial, Lancet. 2010 Feb 6;375(9713):463-74
Durée de l’antibiothérapie Critères secondaires
* Pour 1000 jours
Bouadma L et al; Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial, Lancet. 2010 Feb 6;375(9713):463-74
Evaluer l’efficacité du traitement?
Rau BM, Arch Surg 2007, 142:134
Faut-il prendre en compte tous les germes retrouvés à la culture ?
¡ Complexité des études cliniques ¡ Rôle +++ de la chirurgie
l modalités variables l participation à l’échec thérapeutique
Souvent associations de P. communautaires, de PPO et de P. nosocomiales
+ tableaux cliniques, microbiologie et pronostics
fondamentalement différents
=> Analyse critique de la littérature difficile
Faut-il un traitement actif sur les entérocoques
¡ Commensaux du tube digestif ¡ Concentrations « faibles » ¡ Pouvoir pathogène spontané
modéré ¡ Emergence favorisée par
antibiothérapie
Faut-il un traitement actif sur les entérocoques?
¡ Etude prospective randomisée multicentrique en double aveugle
¡ 330 péritonites secondaires ¡ Ciprofloxacine/métronidazole vs imipénème ¡ Echecs de traitement :
l si prélèvement entérocoque + (71 patients) ¡ 28 % vs 14 % (p<0,01)
l dans le groupe entérocoque + ¡ Ciprofloxacine 13/43 (30%) ¡ Imipénème 7/28 (25%) (NS)
Facteurs indépendants prédictifs d’échec : - score APACHE II > 12 - entérocoque dans le prélèvement initial
Burnett Surgery 1995
Faut-il un traitement actif sur les entérocoques?
¡ 200 infections intra-abdominales ¡ 34 complications à entérocoques:
l abcès de paroi : 20 l PPO : 6 l infections à distance l réinfection : 15 l superinfection = 19
¡ & de la mortalité 21 % vs 4 % (p<0,001)
Sitgès-Serra Br J Surg 2002
Facteurs de risque indépendants d’infection postopératoire à entérocoques : - PPO - APACHE II > 12 - traitement initial inadapté sur les entérocoques
Faut-il un traitement actif sur les entérocoques?
¡ En absence de données fiables dans la littérature
¡ Recommandé en cas l Infection postopératoire l Infection récidivante l Traitement antibiotique préalable
Mazuski JE et al. Surg Infect 2002;3:175-233 Solomkin J et al. Clin Infect Dis 2003;37:997-1005
Antifongiques
l Beaucoup de “candidats” l Peu de candidose invasive (associée à
un mauvais pronostic)
¡ Si indications larges de traitement antifongique: l Modification de l’écologie? l Augmentation des coûts
Candida ¡ Présent dans le tube digestif des sujets
sains ¡ Concerne 50-70% des patients
chirurgicaux/trauma ¡ Concerne 75% des patients ventilés
depuis 7 jours ¡ Le nombre de sites et l’intensité de la
colonisation augmente le risque d’IFI ¡ La colonisation trachéale est le reflet de la
colonisation oropharyngée est n’est pas associée à la pneumonie à candida chez les patient non-neutropénique
Knoke M – Mycoses 1999; Leon et al - Crit Care Med 2006 and Crit Care Med 2009; Charles et al ICM 2005 Pelz Ann Surg 2001; Pittet Ann Surg 1994; Meersseman et al. ICM 2009 ; Giglio Crit Care 2012;
Results
A total of 2411 patient-days of antifungal use wasevaluated in 225 patients [66% male; average age, 62(range: 23–91 years); Table 1]. Among the four insti-tutions, average age was similar. As expected, the VAhospitals averaged a higher proportion of male patients.Although the patients at each institution displayeddifferent comordities, the extent of comorbidities calcu-lated using the Charlson comorbidity index were similaramongst all institutions (range: 3.1–3.7). All patientswere critically ill and either had organ system derange-ments, abnormal vital signs, or laboratory abnormalit-ies, high APACHEII scores and WBC count. Onehundred per cent were concomitantly prescribed anti-biotics. The most common types of surgery sites weregastrointestinal (37%), cardiac (30%) and pulmonary(13%). The median hospital stay was 25 days and thecrude mortality rate was 50%.
Antifungal usage patterns
Fluconazole was the most frequently prescribed anti-fungal agent (1846 patient-days; 221 patients) followedby amphotericin B deoxycholate (251 patient-days; 22patients), lipid formulations of amphotericin B (201patient-days; 24 patients), itraconazole (71 patient-days; five patients), and caspofungin (42 patient-days;one patient; Fig. 1). One patient received voriconazole(four patient-days). Fluconazole was the antifungalprescribed first in 95% of the patients. Intravenousfluconazole therapy was started empirically for 85% ofpatients. Twenty-two per cent of patients received aloading dose of 400–800 mg. Initial dose of fluconazolevaried between the different institutions (Fig. 2). Theinitial dose of fluconazole was most commonly 400 mg
(58% of cases) or 200 mg (32% of cases; range: 100–800 mg). The VA institutions most commonly pre-scribed fluconazole 200 mg initially while the othercentres most commonly prescribed fluconazole 400 mg(P < 0.05). Whereas fluconazole was the most fre-quently prescribed antifungal agent at all four hospitals,lipid formulations of amphotericin B were the secondmost common antifungal agents prescribed in threehospitals, and amphotericin B deoxycholate was thesecond most common agent prescribed in the fourth.Overall, 46% of the amphotericin B prescriptions werefor the lipid-formulation product. The median time tothe start of the initial antifungal regimen was 8 daysfrom admission to the SICU, although the times werehighly variable (range: 0–70 days).
Indication for antifungal therapy
Antifungals were prescribed for empiric coverage incritically ill patients already prescribed antibiotics (44%)
Table 1 Demographic and hospitalinformation of 225 surgical intensive careunits (SICU) patients prescribed antifungalagents by study hospital.
Overall
Hospital type
Generalmedical/surgical
Oncologyspecialty
VAhospital
No. of hospitals 4 1 1 2No. of patients 225 93 80 54Age (mean ± SD) 62 ± 14 64 ± 13 61 ± 14 62 ± 14Gender (%male) 66 54 60 94Charlson comorbidity index 3.4 ± 1.8 3.2 ± 1.8 3.7 ± 2.0 3.1 ± 1.7ApacheII score* (mean ± SD) 15 ± 8 16 ± 6 14 ± 8 17 ± 9Average WBC* (mean ± SD) 15 ± 10 17 ± 10 15 ± 11 12 ± 6Indication for antifungal therapy*Empiric (%) 44 37 40 65Preemptive (%) 43 45 52.5 26Candidiasis (%) 12 26 7.5 9
*Evaluated on the start date of antifungal therapy.
0 500 1000 1500 2000
Voriconazole
Caspofungin
Itraconazole
Lipid-based amphotericin
Amphotericin B
Fluconazole
Patient days of therapy
Figure 1 Overall antifungal usage patterns in 225 surgicalintensive care units (SICU) patients prescribed systemic antifungalagents.
K. W. Garey et al.
228 ! 2006 Blackwell Publishing Ltd • Mycoses, 49, 226–231
Evaluation of antifungals in the surgical intensive care unit:a multi-institutional study
Kevin W. Garey,1 Melinda M. Neuhauser,1 David T. Bearden,2 Joan P. Cannon,3 Russell E. Lewis,1
Layne O. Gentry4 and Dimitrios P. Kontoyiannis5
1Departments of Clinical Science and Administration, University of Houston College of Pharmacy, Houston, TX, 2College of Pharmacy at OHSU, Oregon State
University, Portland, OR, 3Department of Pharmacy, Edward Hines VA Hospital, Hines, IL, 4Infectious Disease Section, St Luke’s Episcopal Hospital, Houston, TX
and 5Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
Summary In the USA, >50% of candidemia episodes occur in medical or surgical intensive careunits (SICU). However, studies focused on patterns and rationale for antifungal use arelacking. The objective of this study was to evaluate systemic antifungal usage in SICUpatients. Retrospective audit of SICU patients receiving antifungal therapy from fourAmerican hospitals. Medical records were reviewed for demographics, hospitalvariables, microbiology results, antifungal regimens and indications for therapy. Atotal of 2411 patient-days of antifungal use were evaluated in 225 patients.Fluconazole was the most frequently prescribed antifungal (1846 patient-days)followed by amphotericin B deoxycholate (251 patient-days), lipid formulations ofamphotericin B (201 patient-days), itraconazole (71 patient-days), and caspofungin(42 patient-days). Antifungals were prescribed empirically (44%), for preemptivetherapy in critically ill patients colonised with Candida (43%), or for candidiasis (12%).Candida species were recovered from 98% of patients with positive fungal cultures mostcommonly from pulmonary (53%) or urinary sources (17%). Fluconazole is the mostfrequently prescribed antifungal agent in SICUs and is most often prescribed for empiricor preemptive indications. Research efforts to identify patients who warrant preemptiveantifungal therapy for invasive candidiasis could dramatically change antifungalprescribing patterns in the SICU.
Key words: antifungal, fluconazole, intensive care unit, pharmacoepidemiology.
Background
Intensive care units (ICUs) are the epicentre of nosoco-mial infections and their associated morbidity, mortal-ity, emerging pathogens and rising health-care costs.1
Recent data from the National Nosocomial InfectionsSurveillance System show that Candida species nowrepresent the fourth most frequently isolated blood-stream pathogen in ICUs.2 In the United States, >50% ofcandidemia episodes occur in surgical or medical ICUs.Prescription of antifungals has also increased, especially
in surgical ICUs (SICUs), along with the introduction ofnew antifungals, such as lipid-based amphotericin B andcaspofungin.3 Because of the lack of sensitive diagnostictests (either culture, serology or antigen detection-based) that detect invasive candidiasis early on incritically ill or immunosupressed patients, cliniciansoften start antifungal therapy empirically or preemp-tively, based on the presence of Candida from non-sterilesites.4 However, no studies have focused on this topic.Therefore, we performed the study described herein toevaluate the patterns of antifungal use in SICU patientsreceiving systemic antifungal agents.
Methods
This study was performed at four hospitals that care fordiverse patient populations [two tertiary care centres
Correspondence: Kevin W. Garey, PharmD, University of Houston College of
Pharmacy, Texas Medical Center, 1441 Moursund St, Houston, TX 77008-
3407, USA. Tel.: 713 795 8386. Fax: 713 795 8383.
E-mail: [email protected]
Accepted for publication 30 November 2005
Original article
226 ! 2006 Blackwell Publishing Ltd • Mycoses, 49, 226–231
2006 Mycoses, 49, 226–231
Patients avec candidose invasive
Prophylaxie Empirique Préemptif CI prouvée
n pts
Probabilité de candidose invasiveD’après Bassetti M SRLF 2013
Stratégies: Réa & Hématologie
Mortalité élevée
fever, and empirical fluconazole treatment did not improve
outcome when compared with placebo [30].
Recommendations. Early treatment of presumed fungaemia is
presumably associated with higher survival rates, but the
optimal time point for initiating empiric antifungal treatment
remains undetermined. Due to lack of data, no recommenda-
tion can be given for choosing a specific drug for fever-dri-
ven therapy. In general, such choice should be based on local
epidemiology and drug–drug interactions in the individual
patient and should be made among the same drugs as rec-
ommended for candidaemia. Further recommendations are
given in Table 4.
Diagnosis-driven approach (pre-emptive)
We defined pre-emptive therapy as therapy triggered by
microbiological evidence of candidiasis without proof of inva-
sive fungal infection.
Evidence. Several studies have addressed diagnosis-driven ther-
apy on grounds of detecting (1,3)-b-D-glucan in serum or
plasma. In a study on 46 ICU patients without infection or with
confirmed bacterial or fungal infection, glucan test results (G-
test; Associates of Cape Cod, East Falmouth, MA, USA) corre-
lated with infection, but not with fungal infection. The authors
suggested using the test to rule out invasive fungal infection
[31]. This was the key finding in a study using the FungitellTM
TABLE 3. Recommendations on antifungal prophylaxis in ICU patients
Population Intention Intervention SoR QoE References Comment
Recent abdominal surgery AND recurrentgastrointestinal perforations oranastomotic leakages
To prevent intraabdominal Candida infection Fluconazole 400 mg/day B I [8] PlaceboN = 43
Caspofungin 70/50 mg/day C IIu [9] Single armN = 19
Critically ill surgical patients with anexpected length of ICU stay ‡3 day
To delay the time to fungal infection Fluconazole 400 mg/day C I [10] PlaceboN = 260
Ventilated for 48 h and expected to beventilated for another ‡72 h
To prevent invasive candidiasis/candidaemia Fluconazole 100 mg/day C I [162] PlaceboN = 204SDD used
Ventilated, hospitalized for ‡3 day, receivedantibiotics, CVC, and ‡1 of: parenteralnutrition, dialysis, major surgery,pancreatitis, systemic steroids,immunosuppression
To prevent invasive candidiasis/candidaemia Caspofungin 50 mg/day C IIa [5] PlaceboN = 186EORTC/MSGcriteria used
Surgical ICU patients To prevent invasive candidiasis/candidaemia Ketoconazole 200 mg/day D I [22] PlaceboN = 57
Critically ill patients with risk factors forinvasive candidiasis/candidaemia
To prevent invasive candidiasis/candidaemia Itraconazole 400 mg/day D I [21] OpenN = 147
Surgical ICU with catabolism To prevent invasive candidiasis/candidaemia Nystatin4 Mio IU/day
D I [20] PlaceboN = 46
SoR, Strength of recommendation; QoE, Quality of evidence; ICU, intensive care unit; CVC, central venous catheter; IU, international units.The table displays the published evidence; therefore, other available antifungal agents are not mentioned here.
TABLE 4. Recommendations on fever-driven and diagnosis-driven therapy of candidaemia and invasive candidiasis
Population Intention Intervention SoR QoE References
Adult ICU patients with fever despitebroad-spectrum antibiotics and APACHEII >16
To resolve fever Fluconazole 800 mg/day D I [30]
ICU patients persistently febrile, but withoutmicrobiological evidence
To reduce overall mortality Fluconazole or echinocandin C IIu [28][163][164][7][27]
ICU patients with candida isolated fromrespiratory secretions
To cure invasive candidiasis or candidaemia early Any antifungal D IIu [42]
ICU patients with positive (1,3)-b-D-glucantesta
To cure invasive candidiasis or candidaemia early Any antifungal C IIu [39][31][37][35][32][36][34][33]
Any patient with Candida isolated froma blood culture
To cure invasive candidiasis Antifungal treatment A II [46][47][48][49]
APACHE, acute physiology and chronic health evaluation.aThe (1,3)-b-D-glucan tests have low specificity and sensitivity with false-positive results in the presence of haemodialysis, other fungal or bacterial infection, wound gauze,albumin or immunoglobulin infusion.
22 Clinical Microbiology and Infection, Volume 18 Supplement 7, December 2012 CMI
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 19–37
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
Patients avec candidose invasive
Prophylaxie Empirique Préemptif CI prouvée
n pts
Probabilité de candidose invasiveD’après Bassetti M SRLF 2013
Stratégies: Réa & Hématologie
Mortalité élevée
Evidence. Patients who had undergone abdominal surgery
recently and who had recurrent gastrointestinal perforations
or anastomotic leakages were treated either with fluconaz-
ole 400 mg/day or with placebo in order to prevent intraab-
dominal Candida infection. The rate of intraabdominal
candidiasis was significantly lower in the fluconazole prophy-
laxis group. This clinical trial exhibited high technical quality,
but was performed in a very high baseline incidence popula-
tion and is limited by enrolling 43 evaluable patients only
[8]. In a small non-comparative trial, standard dosed caspo-
fungin was evaluated in the same indication, but no evidence
can be derived [9]. In a large prophylaxis trial, critically ill
surgical patients with an expected ICU stay of ‡3 days were
randomized to receive either fluconazole 400 mg/day or pla-
cebo. The primary endpoint was the time to fungal infection,
which was significantly delayed in the fluconazole prophylaxis
group. The trial was well designed and enrolled 260 patients.
A limitation of the study is the inclusion of presumed inva-
sive fungal infection, defined for example, by repeatedly
positive urine cultures and catheter tips with ‡15 yeast col-
onies, into the primary endpoint [10]. In another study,
patients ventilated for 48 h and expected to remain venti-
lated for another ‡72 h received selective digestive decon-
tamination with polymyxin B, neomycin and vancomycin and
were randomized to receive fluconazole 100 mg/day or pla-
cebo. This trial was well designed, and 204 patients were
randomized. Candidaemia was more successfully prevented
in fluconazole recipients, but the selective digestive decon-
tamination regimen used in this clinical trial is not a standard
in most countries [11–13]. Meta-analyses of the clinical trials
above and some other studies on highly selected populations
found fluconazole 400 mg/day to be superior to placebo in
preventing invasive fungal infection in critically ill surgical
patients [14–18]. A more recent clinical trial compared ca-
spofungin 50 mg/day with placebo for prophylaxis in a highly
selected population of ventilated patients receiving antibiot-
ics, having a central venous catheter and fulfilling at least
one of the following criteria: parenteral nutrition, dialysis,
major surgery, pancreatitis, systemic steroids or other
immunosuppressant medication. The primary endpoint of
this trial was the incidence of proven and probable invasive
candidiasis according to EORTC/MSG definitions [19]. The
investigators found a trend only towards a reduced inci-
dence of invasive candidiasis [5]. Other antifungals have been
evaluated in prophylactic indications [20–22]. For ketoconaz-
ole 200 mg/day, evidence of prophylactic benefit is weak
while adverse events and drug interactions limit its use in
general [22]. The same is true for itraconazole 400 mg/day
[21]. Nystatin 4 Mio IU/day has been evaluated, but concept
and patient setting are basically outdated [20]. Intravenous
amphotericin B and the echinocandins have not been suffi-
ciently evaluated in this indication [23]. Antifungal prophy-
laxis in solid organ transplant recipients is not part of this
guideline.
Of note, none of the trials proved a reduction in overall
or attributable mortality. All trials were lacking power to
address the potential emergence of less azole-susceptible
strains during prophylaxis. Apart from historical control
studies in intensive care and abdominal surgical populations,
this has been shown in prophylactic settings in haematology
during substantially longer azole exposure periods [24–26].
Selection of less-susceptible strains remains a caveat against
broadly using antifungals in populations where substantial
benefit has not been proven.
Recommendations. Fluconazole prophylaxis against invasive
candidiasis is recommended in patients who recently under-
went abdominal surgery and had recurrent gastrointestinal
perforations or anastomotic leakages. For further recom-
mendations, refer to Table 3.
Fever-driven approach (empiric)
We defined empiric therapy as a fever-driven approach in
the clinical situation of a patient at risk for invasive candidia-
sis who is persistently febrile with no microbiological evi-
dence of infection.
Evidence. The value of initiating antifungal therapy in this situa-
tion has been addressed in a number of retrospective studies.
Incubation time [27] and time from first positive blood culture
drawn to initiation of empiric antifungal therapy correlated
with mortality increases [6,28]. Similarly, in a population-
based retrospective study, empiric antifungal treatment was
associated with higher survival rates, if the isolate turned out
to be susceptible to the empiric regimen [29]. Another retro-
spective study in patients with septic shock due to any cause
found empiric antifungal therapy was given infrequently, and
those with invasive fungal infection not receiving empiric anti-
fungals had a statistically significantly higher mortality [7].
Although uncontrolled, all of these studies suggest that ini-
tiating empiric therapy may be beneficial to reduce overall
mortality, but none could identify reliable triggers for
antifungal treatment. They analysed patients with candidaemia
but not the whole population of febrile patients.
One randomized double-blind placebo-controlled clinical
trial evaluated fluconazole 800 mg/day in 270 adult ICU
patients with an APACHE II score >16. Rates of invasive can-
didiasis were not statistically different between the two
groups. The primary endpoint was driven by resolution of
CMI Cornely et al. Diagnosis and management of Candida diseases 2012 21
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 19–37
fever, and empirical fluconazole treatment did not improve
outcome when compared with placebo [30].
Recommendations. Early treatment of presumed fungaemia is
presumably associated with higher survival rates, but the
optimal time point for initiating empiric antifungal treatment
remains undetermined. Due to lack of data, no recommenda-
tion can be given for choosing a specific drug for fever-dri-
ven therapy. In general, such choice should be based on local
epidemiology and drug–drug interactions in the individual
patient and should be made among the same drugs as rec-
ommended for candidaemia. Further recommendations are
given in Table 4.
Diagnosis-driven approach (pre-emptive)
We defined pre-emptive therapy as therapy triggered by
microbiological evidence of candidiasis without proof of inva-
sive fungal infection.
Evidence. Several studies have addressed diagnosis-driven ther-
apy on grounds of detecting (1,3)-b-D-glucan in serum or
plasma. In a study on 46 ICU patients without infection or with
confirmed bacterial or fungal infection, glucan test results (G-
test; Associates of Cape Cod, East Falmouth, MA, USA) corre-
lated with infection, but not with fungal infection. The authors
suggested using the test to rule out invasive fungal infection
[31]. This was the key finding in a study using the FungitellTM
TABLE 3. Recommendations on antifungal prophylaxis in ICU patients
Population Intention Intervention SoR QoE References Comment
Recent abdominal surgery AND recurrentgastrointestinal perforations oranastomotic leakages
To prevent intraabdominal Candida infection Fluconazole 400 mg/day B I [8] PlaceboN = 43
Caspofungin 70/50 mg/day C IIu [9] Single armN = 19
Critically ill surgical patients with anexpected length of ICU stay ‡3 day
To delay the time to fungal infection Fluconazole 400 mg/day C I [10] PlaceboN = 260
Ventilated for 48 h and expected to beventilated for another ‡72 h
To prevent invasive candidiasis/candidaemia Fluconazole 100 mg/day C I [162] PlaceboN = 204SDD used
Ventilated, hospitalized for ‡3 day, receivedantibiotics, CVC, and ‡1 of: parenteralnutrition, dialysis, major surgery,pancreatitis, systemic steroids,immunosuppression
To prevent invasive candidiasis/candidaemia Caspofungin 50 mg/day C IIa [5] PlaceboN = 186EORTC/MSGcriteria used
Surgical ICU patients To prevent invasive candidiasis/candidaemia Ketoconazole 200 mg/day D I [22] PlaceboN = 57
Critically ill patients with risk factors forinvasive candidiasis/candidaemia
To prevent invasive candidiasis/candidaemia Itraconazole 400 mg/day D I [21] OpenN = 147
Surgical ICU with catabolism To prevent invasive candidiasis/candidaemia Nystatin4 Mio IU/day
D I [20] PlaceboN = 46
SoR, Strength of recommendation; QoE, Quality of evidence; ICU, intensive care unit; CVC, central venous catheter; IU, international units.The table displays the published evidence; therefore, other available antifungal agents are not mentioned here.
TABLE 4. Recommendations on fever-driven and diagnosis-driven therapy of candidaemia and invasive candidiasis
Population Intention Intervention SoR QoE References
Adult ICU patients with fever despitebroad-spectrum antibiotics and APACHEII >16
To resolve fever Fluconazole 800 mg/day D I [30]
ICU patients persistently febrile, but withoutmicrobiological evidence
To reduce overall mortality Fluconazole or echinocandin C IIu [28][163][164][7][27]
ICU patients with candida isolated fromrespiratory secretions
To cure invasive candidiasis or candidaemia early Any antifungal D IIu [42]
ICU patients with positive (1,3)-b-D-glucantesta
To cure invasive candidiasis or candidaemia early Any antifungal C IIu [39][31][37][35][32][36][34][33]
Any patient with Candida isolated froma blood culture
To cure invasive candidiasis Antifungal treatment A II [46][47][48][49]
APACHE, acute physiology and chronic health evaluation.aThe (1,3)-b-D-glucan tests have low specificity and sensitivity with false-positive results in the presence of haemodialysis, other fungal or bacterial infection, wound gauze,albumin or immunoglobulin infusion.
22 Clinical Microbiology and Infection, Volume 18 Supplement 7, December 2012 CMI
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 19–37
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
Candida Score Ø Candida score:
0.908(NPT) + 0.997(patient chirurgical) + 1.112(colonisation)+2.038(sepsis grave)
Ø Candida score arrondi: NPT+ chirurgie + colonisation + 2* SEPSIS GRAVE Chaque item vaut 1 point s’il est positif
Leon, Crit Care Med, 2006
Leon et al - Crit Care Med 2006; 34:730–737 and Crit Care Med 2009; 37:1624 –1633
PPV (Candida score)=Proba (Dis+/CS +) = 13.8%…PPV (Colonization index)=Proba (Dis/CI+) = 8.7%…
Candida score 㻠㻠㻠㻠3 (95% CI)
Colonization index 㻠㻠㻠㻠0.5(95% CI)
Area under ROC curve 0.774 (0.715-0.832) 0.633 (0.557-0.709)
Sensitivity 77.6 (66.9-88.3) 72.4 (60.0-83.9)
Specificity 66.2 (63.0-69.4) 47.4 (44.0-50.8)
Positive predictive value 13.8 (10.0-17.5) 8.7 (6.2-11.3)
Negative predictive value 97.7 (96.4-98.9) 96.1 (94.2-98.0)
Relative risk for invasive candidiasis 5.98 (3.28-10.92) 2.24 (1.28-3.93)
Candida score (>7 jours)• Construction n =1699 pts (Leon CCM 2006)
– Parenteral nutrition 1pt OR = 2,48 IC95:1,16 - 5,31– Surgical admission 1pt OR = 2,71 IC95:1,45 - 5,06– Multiple Colonization 1pt OR = 3,04 IC95:1,45 - 6,39– Severe sepsis 2pts OR = 7,68 IC95:4,14 - 14,22
• External Validation n =1107 pts (Leon CCM 2009)
Leon et al - Crit Care Med 2006; 34:730–737 and Crit Care Med 2009; 37:1624 –1633
Autre score prédictif
• Localisation sus mésocolique de la perforation • L’existence d’une antibiothérapie de plus de
48H en cours • Un état de choc lors de la chirurgie • Sexe féminin
⇒ Un score > ou = à 3 a une sensibilité de 84% et une spécificité de 50%
⇒ La présence d’un examen positif à levure dans le liquide péritonéal (témoignant indirectement de l’intensité de l’inoculum) est indépendamment associé à la mortalité dans une série de péritonites à levures
Dupont H, Crit Care Med2003 Dupont H, Arch Surg2002
Biomarqueurs
Etude Test Se et Sp Mikuska M (CC 2010) 14 études
Mananne / Antimanne
83% et 86% > Pour C. albicans
Karageorgopoulos DE (CID 2011) 11 études
β-D-glucan 75 et 85% (voire moins dans d’autres études) Faux +
Peu de données Septifast ??? Avni T (JCM 2011) 54 études
PCR 95 et 92%
Biomarqueurs
Clancy CJ et al Clin Infect Dis 2013Clancy CJ et al Clin Infect Dis 2013
Biomarqueurs
Clancy CJ et al Clin Infect Dis 2013
CID 2009
fever, and empirical fluconazole treatment did not improve
outcome when compared with placebo [30].
Recommendations. Early treatment of presumed fungaemia is
presumably associated with higher survival rates, but the
optimal time point for initiating empiric antifungal treatment
remains undetermined. Due to lack of data, no recommenda-
tion can be given for choosing a specific drug for fever-dri-
ven therapy. In general, such choice should be based on local
epidemiology and drug–drug interactions in the individual
patient and should be made among the same drugs as rec-
ommended for candidaemia. Further recommendations are
given in Table 4.
Diagnosis-driven approach (pre-emptive)
We defined pre-emptive therapy as therapy triggered by
microbiological evidence of candidiasis without proof of inva-
sive fungal infection.
Evidence. Several studies have addressed diagnosis-driven ther-
apy on grounds of detecting (1,3)-b-D-glucan in serum or
plasma. In a study on 46 ICU patients without infection or with
confirmed bacterial or fungal infection, glucan test results (G-
test; Associates of Cape Cod, East Falmouth, MA, USA) corre-
lated with infection, but not with fungal infection. The authors
suggested using the test to rule out invasive fungal infection
[31]. This was the key finding in a study using the FungitellTM
TABLE 3. Recommendations on antifungal prophylaxis in ICU patients
Population Intention Intervention SoR QoE References Comment
Recent abdominal surgery AND recurrentgastrointestinal perforations oranastomotic leakages
To prevent intraabdominal Candida infection Fluconazole 400 mg/day B I [8] PlaceboN = 43
Caspofungin 70/50 mg/day C IIu [9] Single armN = 19
Critically ill surgical patients with anexpected length of ICU stay ‡3 day
To delay the time to fungal infection Fluconazole 400 mg/day C I [10] PlaceboN = 260
Ventilated for 48 h and expected to beventilated for another ‡72 h
To prevent invasive candidiasis/candidaemia Fluconazole 100 mg/day C I [162] PlaceboN = 204SDD used
Ventilated, hospitalized for ‡3 day, receivedantibiotics, CVC, and ‡1 of: parenteralnutrition, dialysis, major surgery,pancreatitis, systemic steroids,immunosuppression
To prevent invasive candidiasis/candidaemia Caspofungin 50 mg/day C IIa [5] PlaceboN = 186EORTC/MSGcriteria used
Surgical ICU patients To prevent invasive candidiasis/candidaemia Ketoconazole 200 mg/day D I [22] PlaceboN = 57
Critically ill patients with risk factors forinvasive candidiasis/candidaemia
To prevent invasive candidiasis/candidaemia Itraconazole 400 mg/day D I [21] OpenN = 147
Surgical ICU with catabolism To prevent invasive candidiasis/candidaemia Nystatin4 Mio IU/day
D I [20] PlaceboN = 46
SoR, Strength of recommendation; QoE, Quality of evidence; ICU, intensive care unit; CVC, central venous catheter; IU, international units.The table displays the published evidence; therefore, other available antifungal agents are not mentioned here.
TABLE 4. Recommendations on fever-driven and diagnosis-driven therapy of candidaemia and invasive candidiasis
Population Intention Intervention SoR QoE References
Adult ICU patients with fever despitebroad-spectrum antibiotics and APACHEII >16
To resolve fever Fluconazole 800 mg/day D I [30]
ICU patients persistently febrile, but withoutmicrobiological evidence
To reduce overall mortality Fluconazole or echinocandin C IIu [28][163][164][7][27]
ICU patients with candida isolated fromrespiratory secretions
To cure invasive candidiasis or candidaemia early Any antifungal D IIu [42]
ICU patients with positive (1,3)-b-D-glucantesta
To cure invasive candidiasis or candidaemia early Any antifungal C IIu [39][31][37][35][32][36][34][33]
Any patient with Candida isolated froma blood culture
To cure invasive candidiasis Antifungal treatment A II [46][47][48][49]
APACHE, acute physiology and chronic health evaluation.aThe (1,3)-b-D-glucan tests have low specificity and sensitivity with false-positive results in the presence of haemodialysis, other fungal or bacterial infection, wound gauze,albumin or immunoglobulin infusion.
22 Clinical Microbiology and Infection, Volume 18 Supplement 7, December 2012 CMI
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 19–37
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
Patients avec candidose invasive
Prophylaxie Empirique Préemptif CI prouvée
n pts
Probabilité de candidose invasiveD’après Bassetti M SRLF 2013
Stratégies: Réa & Hématologie
Mortalité élevée
Faut-il un traitement actif sur Candida ?
¡ Etude cas (n = 58)-témoin (n = 108)
¡ Isolement de Candida sp dans les PPO : l facteur de risque indépendant de
mortalité l de la durée de ventilation l durée de séjour l nombre de reprises chirurgicales
Dupont IDSA 2001
Faut-il un traitement actif sur Candida ?
Montravers P et al; A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units; Clin Microbiol Infect. 2011 Jul;17(7):1061-7
Fluconazole TRIFLUCAN
Itraconazole SPORANOX
Voriconazole VFEND
Amphotéricine B AMBISOME ABELCET FUNGIZONE
5-FC ANCOTIL
Echinocandines CASPOFUNGINE
C. Albicans
C. Tropicalis
C. Parapsilosis
C. glabrata
C. Krusei
C lusitaniae Asp. fumigatus
Asp. niger
Asp. terreus
Asp. flavus
Zygomycetes Sp Cryptococcus neoformans
Sensible Intermédiaire Résistant
Fungistatique Fungicide
the proportion of patients receiving which type of lipid-based
amphotericin B formulation.
The combination of amphotericin B deoxycholate and
fluconazole has been as effective as fluconazole monotherapy
in a randomized trial, but patients had an increased risk of
toxicity and no survival benefit [74]. A small study (N = 72)
comparing fluconazole with amphotericin B deoxycholate
and 5-flucytosine showed no difference in overall response
to treatment [75].
Recommendations. Targeted treatment of candidaemia with
echinocandins is strongly recommended. The recommenda-
tion for liposomal amphotericin B or voriconazole is less
stringent, and fluconazole is recommended with marginal
strength only, except for C. parapsilosis. For detailed recom-
mendations, refer to Table 5.
Duration of targeted treatment, step-down to oral treat-
ment and diagnostics in candidaemia
Evidence. The duration of treatment depends on the extent
of organ involvement. In a population without documented
organ involvement, treatment aims to clear the infection
and at the same time to avoid deep-organ involvement. This
can be achieved by treating for 14 days after the end of
candidaemia [82]. To determine the end of candidaemia, at
least one blood culture per day should be taken until cul-
ture results come back negative. Treatment can probably
be simplified by stepping down to oral fluconazole after
10 days of intravenous treatment, if the patient is stable,
tolerates the oral route and if the species is susceptible
[55,63,64].
The diagnostic procedures to detect organ involvement
comprise transoesophageal echocardiography, fundoscopy
and search for a thrombus. A recent observational study
found infectious endocarditis in 8.3% of patients with candi-
daemia; the majority of these patients had no well-estab-
lished risk factors, that is, vascular prosthesis or persistent
candidaemia [83].
Some prospective studies addressed ocular candidiasis as
complication of candidaemia. The diagnostic approach was
usually based on weekly eye examinations. Immunosuppres-
sion and repeatedly positive blood cultures are risk factors
TABLE 5. Recommendations on initial targeted treatment of candidaemia and invasive candidiasis in adult patients
Intervention SoR QoE References Comment
Anidulafungin 200/100 mg A I [64] Consider local epidemiology (Candida parapsilosis, Candida krusei), lessdrug–drug interactions than caspofungin
Caspofungin 70/50 mg A I [67][55][63]
Consider local epidemiology (C. parapsilosis)
Micafungin 100 mg A I [61][63]
Consider local epidemiology (C. parapsilosis), less drug–drug interactionsthan caspofungin, consider EMA warning label
Amphotericin B liposomal 3 mg/kg B I [61][62]
Similar efficacy as micafungin, higher renal toxicity than micafungin
Voriconazole 6/3 mg/kg/daya,b B I [43][78][77]
Limited spectrum compared to echinocandins, drug–drug interactions,limitation of IV formulation in renal impairment, consider therapeutic drugmonitoring
Fluconazole 400–800 mga C I [165][53][74][54][64][76][75][73][72]
Limited spectrum, inferiority to anidulafungin (especially in the subgroupwith high APACHE scores), may be better than echinocandins againstC. parapsilosis
Amphotericin B lipid complex 5 mg/kg C IIa [57][58]
Amphotericin B deoxycholate 0.7–1.0 mg/kg D I [50][51][165][53][54][55]
Substantial renal and infusion-related toxicity
Amphotericin B deoxycholate plus fluconazole D I [74] Efficacious, but increased risk of toxicity in ICU patientsNo survival benefit
Amphotericin B deoxycholate plus 5-fluorocytosine D II [75]Efungumab plus lipid-associated amphotericin B D II [166]Amphotericin B colloidal dispersion D IIa [60]Itraconazole D IIa [76]Posaconazole D III No reference found
EMA, European Medicines Agency.Comparative clinical trials did not prove a survival benefit of one treatment over another. Primary intention of treating candidaemia is clearing the blood stream.aNot all experts agreed, SoR results from a majority vote.bThe licensed maintenance dosing is 4 mg/kg/day.
CMI Cornely et al. Diagnosis and management of Candida diseases 2012 25
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 19–37
ESCMID* guideline for the diagnosis and management of Candida
diseases 2012: non-neutropenic adult patients
O. A. Cornely1!, M. Bassetti2!, T. Calandra3!, J. Garbino4!, B. J. Kullberg5!, O. Lortholary6,7!, W. Meersseman8!, M. Akova9,
M. C. Arendrup10, S. Arikan-Akdagli11, J. Bille3, E. Castagnola12, M. Cuenca-Estrella13, J. P. Donnelly5, A. H. Groll4, R. Herbrecht15,
W. W. Hope16, H. E. Jensen17, C. Lass-Florl18, G. Petrikkos19, M. D. Richardson20, E. Roilides21, P. E. Verweij5, C. Viscoli22 and
A. J. Ullmann23 for the ESCMID Fungal Infection Study Group (EFISG)
1) Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Koln, BMBF 01KN1106, Center for Integrated Oncology CIO KolnBonn, Cologne Excel-
lence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), German Centre for Infection Research, University of Cologne, Cologne, Ger-
many, 2) Santa Maria Misericordia University Hospital, Udine, Italy, 3) Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire
Vaudois and University of Lausanne, Lausanne, Switzerland, 4) University Hospitals Geneva, Geneva, Switzerland, 5) Radboud University Nijmegen Medical Cen-
tre, Nijmegen, The Netherlands, 6) Service des Maladies Infectieuses et Tropicales, Hopital Necker-Enfants Malades, APHP, Centre d’Infectiologie Necker-
Pasteur, IHU Imagine, Universite Paris Descartes, Paris, 7) Institut Pasteur, Centre National de Reference Mycologie et Antifongiques, Unite de Mycologie Molecu-
laire, CNRS URA3012, Paris, France, 8) University Hospital Gasthuisberg, Leuven, Belgium, 9) Department of Medicine, Hacettepe University School of Medicine,
Ankara, Turkey, 10) Statens Serum Institut, Copenhagen, Denmark, 11) Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara,
Turkey, 12) Instituto Giannina Gaslini, Children’s Hospital, Genova, Italy, 13) Centro Nacional de Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain,
14) Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany, 15) Hopital
de Hautepierre, University of Strasbourg, Strasbourg, France, 16) Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Phar-
macology, University of Liverpool, Liverpool, UK, 17) University of Copenhagen, Frederiksberg, Denmark, 18) Division of Hygiene & Medical Microbiology, Inns-
bruck Medical University, Innsbruck, Austria, 19) 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 20)
Mycology Reference Centre, University Hospital of South Manchester and Manchester Academic Health Science Centre, University of Manchester, Manchester,
UK, 21) Third Department of Pediatrics, Aristotle University School of Medicine and Hippokration Hospital, Thessaloniki, Greece, 22) University of Genoa, IRCCS
San Martino_IST, Genoa, Italy and 23) Department of Internal Medicine II, Julius-Maximilians-University, Wurzburg, Germany
Abstract
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be sum-
marized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastroin-
testinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For
the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconaz-
ole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of
14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treat-
ment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of
indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be
preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native
valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifun-
gal regimen of choice is liposomal amphotericin B +/) flucytosine. In ocular candidiasis, liposomal amphotericin B +/) flucytosine is rec-
ommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives.
Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Keywords: Candidiasis, Guideline, non-neutropenic, prophylaxis, treatment
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
Corresponding authors: O. A. Cornely, Department I for Internal Medicine, University of Cologne, 50924 Cologne, Germany
E-mail: [email protected]
A. J. Ullmann, Infectious Diseases, Department of Internal Medicine II, Julius-Maximilians-University, Oberdurrbacher Str. 6, 97080 Wurzburg, Germany
E-mail: [email protected]
This guideline was presented in part at ECCMID 2011.*European Society for Clinical Microbiology and Infectious Diseases.!Members of the subgroup committee mainly responsible setting up this manuscript.
ª2012 The Authors
Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases
ESCMID PUBLICATIONS 10.1111/1469-0691.12039
Candidoses invasive: tt initialIDSA 2009* ATS2011** ESCMID2012
***Candines A1 et si instable ou
azolés avant (A3)Stable B2
Instable: B3A1
Fluconazole A1 sauf si instable (A3)
Stable: B2Instable: B3
C1
Voriconazole Non Instable: B3 B1
AmB-D Si intolérance aux autres
Instable: B3 D1
AmB-L Idem + coût Instable: B3 B1
Association Non B3 (AmB + fluco D1
* Clin Infect Dis 2009, ** AJRCCM 2011, *** CMI, in press
Traitement initial
* Clin Infect Dis 2009, ** AJRCCM 2011, *** CMI, in press
¡ Définition ¡ Lésion initiale ¡ Physiopathologie ¡ Microbiologie ¡ Diagnostic ¡ Prise en charge
l Traitement chirurgical l Traitement antibiotique l Traitements associés
Traitements associés
¡ Correction de la défaillance hémodynamique +++
¡ Ac anti-endotoxines?
¡ Voie des récepteurs Toll?
¡ Hémofiltration (Haut Volume)?
¡ Adsorption? (hémoperfusion sur membrane Polymixine B)
McCloskey RV et al Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group. Ann Intern Med
1994;121:1-5.
Takeuchi O et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999;11: 443-51.
De Vriese AS et al: Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 1999;10:846-53
IVOIRE
Polystyrene Fiber
polymyxin B
Endotoxin
Polymyxine B
Blood flow
Polymyxine B incorporée à des fibres de polystyrène au sein d’une membrane pouvant être utilisée au cours d’une circulation extra-
corporelle
Traitements associés
Cruz DN et al Early use of Polymyxin B hemoperfusion in abdominal septic shock. The EUPHAS randomized controlled trial. JAMA 2009;301:2445 2452
Traitements associés Etude EUPHAS: 64 patients randomisés
-34 hémoperfusions
-30 traitements conventionnels
Cruz DN et al Early use of Polymyxin B hemoperfusion in abdominal septic shock. The EUPHAS randomized controlled trial. JAMA 2009;301:2445 2452
Traitements associés
Conclusion
¡ Inoculum lourd
¡ Traitement chirurgical: l lavage-drainage+++
¡ Infection polymicrobienne: l traitement à large spectre l Traitement actif sur les entérobactéries l Traitement actif sur les anaérobies
¡ Délai de prise en charge +++