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Antibiothèrapie des PAC à germes atypiques

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Antibiothèrapie des PAC à germes atypiques

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Antibiothèrapie des PAC à germes atypiques

  1. 1. Antibiothérapie des PAC à germes atypiques Jordi Roig Hospital N. Sra. de Meritxell, Pneumologie ANDORRA 15ème Conférence de Consensus en Thérapeutique Anti-infectieuse, Paris, 2006
  2. 2. Traitement des PAC à germes atypiques: difficultés  Le manque de standardisation des méthodes in- vitro, cellulaires et in-vivo (modèle animal)  Souvent, manque d’essais cliniques randomisés  Recommandations souvent basées sur l’expérience clinique d’études observationnelles  Doutes ou erreurs méthodologiques fréquents dans ce genre d’études  Valeur réelle d’autres mesures thérapeutiques hormis l’antibiothérapie?
  3. 3. PAC à germes atypiques: Est-il vraiment nécessaire de couvrir les agents atypiques?  Mills GD. BMJ 2005. Le risque d’échec du traitement est bas (risque relatif 0.4) si Legionella est correctement traitée  Shefet D. Arch Intern Med 2005. Pour les PAC hospitalisées, le bénéfice de couvrir les agents atypiques dérive aussi du groupe de patients atteints de Legionella  Roson B. Arch Intern Med 2004. Pour les PAC hospitalisées, l’échec du traitement précoce est associé à Legionella.
  4. 4. Legionella: implications thérapeutiques  Il existe uniquement de bonnes méthodes diagnostiques pour Legionella sérogroupe 1  Les caractéristiques cliniques, radiologiques et de laboratoire sont souvent superposables à d’autres pneumonies causées par des agents non-atypiques comme St.pneumoniae
  5. 5. Thérapie recommandée en ML1 Agent antimicrobien Dosage Route Macro-azalides2 Azithromycin4 Clarithromycin Spiramycine Erythromycine3 500 mg chaque 24 h 500 mg chaque 12 h 1,5 M UI chaque 8 h 6 à 9 M UI (dose totale jour) 1 g chaque 6-8 h IV, p.o. IV, p.o. IV p.o. IV, p.o. Tetracyclines Doxycycline 100 mg chaque 12-24 h IV, p.o. Fluoroquinolones Levofloxacin4 Moxifloxacin4 Gemifloxacin5 Gatifloxacin5 Ciprofloxacin 500-750 mg chaque 24 h 400 mg chaque 24 h 320 mg chaque 24 h 200-400 mg chaque 24 h 400-750 mg chaque 12 h IV, p.o. IV, p.o. p.o. IV, p.o. IV, p.o. Ketolides Telithromycin5 800 mg chaque 24 h p.o. 1 Thérapie orale uniquement en non hospitalisés 2 Cas bénins: autres macrolides oraux sont possibles 3 Moins actif, risque d’effets secondaires 4 Recommandé chez les plus sévères, surtout immunodéprimés 5 Expérience clinique limitée: cas modérés
  6. 6. Traitement de ML: Macrolides vs quinolones  Meilleure activité intrinsèque globalement pour les nouvelles quinolones  Meilleure activité pour les nouveaux macrolides  Azithromycine supérieure aux autres macrolides  Nouvelles quinolones montrent une meilleure clearance bactérienne  Souches de R-ciprofloxacin isolées in vitro en Hongrie2  Inflammation: inférieure pour azithromycine et supérieure pour erythromycin  Azithromycine et quinolones: meilleure PC et PD profile et inhibition irréversible
  7. 7. GROUP 1 (Macrolides) N=76 GROUP 2 (Fluoroquinolones) N=54 p TIME TO APYREXIA (range) h 77.1 (24-408) 48 (24-192) 0.000 BREAKDOWN OF IV vs ORAL THERAPY (range) days 5.3 (3-19) 3.9 (3-10) 0.000 CLINICAL AND X-RAY COMPLICATIONS 18 (23.6%) 9 (16.6%) 0.4 PLEURAL EFFUSION 13 (17.1%) 5 (9.2%) 0.2 EMPYEMA 1 (1.3%) 0 (0%) 1 MECHANICAL VENTILATION 5 (6.5%) 3 (5.5%) 1 SEPTIC SHOCK 6 (7.8%) 3 (5.5%) 0.7 CAVITATION 0 0 MORTALITY 6 (7.8%) 3 (5.5%) 0.7 HOSPITAL STAY (range) days 9.9 (2-59) 7.6 (1-19) 0.09 Sabria M et al. Fluoroquinolones vs macrolides in the treatment of Legionnaire’s disease. Chest 2005;128:1401-1405.
  8. 8. Thérapie Combinée?  Macrolide + rifampicine: traitement standard combiné  Risque de hépatotoxicité réversible avec rifampicine  Macrolides + quinolones: activité synergique in vitro  Etude rétrospective suggère un rôle potentiel de la combinaison pefloxacin et erythromycin  Mortalité de 33% en séries sévères en utilisant une thérapie de macrolides anciens + quinolones anciennes
  9. 9. Etiology in patients with SCAP and microbiologic documentation: CAPUCI study Bodí M et al. Antibiotic prescription for CAP in ICU. CAPUCI study. CID 2005. Microorganisms Overall (N = 297) Immunocompetent patients (N = 248) S. pneumoniae Legionella sp. H. Influenzae P. aeruginosa MS S. aureus MR S. aureus GNB* Pneumocystis M. tuberculosis Varicella zoster Aspergillus sp. Nocardia sp. Other** 143 (48.1%) 23 (7.7%) 22 (7.4%) 20 (6.7%) 16 (5.4%) 3 (1.0%) 18 (6.1%) 10 (3.4%) 8 (2.7%) 8 (2.7%) 1 (0.3%) 1 (0.3% 24 (8.1%) 126 (50.8%) 20 (8.1%) 19 (7.7%) 16 (6.5%) 12 (4.8%) 3 (1.2%) 13 (5.2%) 6 (2.4%) 5 (2.0%) 8 (3.2%) 1 (0.4%) - 19 (7.7%)
  10. 10. RÉSUMÉ DE LEGIONELLA-CAPUCI STUDY  Apparition rapide d’infiltrés radiologiques très fréquente (81%) pour les ML sévères dans les USI  Paramètres de sévérité (APACHE, VM) sont prédictifs de mortalité  Immunocompétence, shock et échec rénal aigu sont associés à un risque supérieur de décès mortalité  Pas de variables identifiées associées au shock  MPOC et maladie cardiaque sont associées à échec rénal aigu: impact des mesures préventives chez ces patients  Diabète est aussi un paramètre potentiel de décès  Thérapie combinée: meilleure option pour ML sévère
  11. 11. ML sévère: analyse de base n=23  La plupart des patients (20) immunocompétents  Patients avec ML: plus jeunes  Patients avec ML: antibiothérapie précédente significativement plus fréquente que pour les patients avec SPAC causées par pneumococcus  Ventilation mécanique: 17 (74%)  Ventilation non invasive : 4 (17.4%)  Pas de ventilation: 2 (8.6%)  Mortalité (EMO) 26 % (6/23). 3 cas de décès, un d’eux immunocompétent, avec Rx initiale inadéquate
  12. 12. ML sévère: Gacouin A. Intensive Care Med 2002  Cas de poussée épidémique inclus  Cas nosocomiaux aussi inclus  < 5% patients diabétiques  Ventilation mécanique: 20.9%  Pas de ventilation: 79.1%  Taux de mortalité: 33 %  Macrolides anciens: erythromycin, spiramycin  Quinolones anciennes: ofloxacin, peflo, cipro  Rifampicine en 2 cas seulement  Monothérapie en 5 cas
  13. 13. 806040200 DAYS 1,0 0,8 0,6 0,4 0,2 0,0 CumulatedSurvival MONOTHERAPY- censured COMBINED- censured MONOTHERAPY COMBINED RX Kaplan – Meier survival curve P=0.203 (Log Rank)
  14. 14. Traitement de la ML: points-clé  Eviter une thérapie courte chez l’immunodéprimé  Endocardite et immunosuppression: thérapie longue  ML sévère peut répondre mal  Nécessité de drainage pour collections purulentes  Pas de résistances dans les cas bien documentés de persistance ou récurrence  Administration précoce d’antibiotique effectif  Possibilité d’infection mixte chez l’immunodéprimé  Thérapie par stéroïdes en cas sélectionnés?  Traitement combiné chez les cas plus sévères
  15. 15. Mycoplasma pneumoniae  Macrolides et doxycicline: première option par l’expérience clinique  Kétolides et fluoroquinolones aussi effectifs  De préférence, à administrer les 5 premiers jours  Traitement pendant 12 à 14 jours pour diminuer le risque de récidive (exception: azythromicine)  L’apparition de résistances ne suppose pas un problème clinique actuellement  Réponse thérapeutique toujours basée sur évolution clinique
  16. 16. Chlamydia pneumoniae  Son rôle véritable comme agent unique ou co- infectieux est encore en discussion  On utilise les mêmes antibiotiques que pour Mycoplasma pneumoniae  Les fluoroquinolones plus récentes montrent une activité intrinsèque supérieure aux antérieures  La toux après pneumonie (HRB) n’est pas susceptible d’antibiothérapie prolongée

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