Les r gles de l art en mati re d antibioprophylaxie

1. Les règles de l’art en matière d’antibioprophylaxie Isabelle Cochereau Fondation Rothschild Hôpital Bichat Paris

2. Incidence des endophtalmies post-opératoires Segment antérieur Cataracte 0,072% - 0,2% - 0,3% Greffe de cornée 0,11% - 0,77% Glaucome 0,061% Segment postérieur Vitrectomie 0,051% Kattan, Ophthalmology 1991, 98, 227-238 Javitt, Arch Ophthalmol 1991, 109, 1085-1089 Aiello, Arch Ophthalmol 1993, 111, 509-513 Salvanet-Bouccara, J Fr Ophtalmol, 1992

3. Antibioprophylaxie DURABLE : principes Traiter un grand nombre de patients sains ? Efficacité démontrée ou présumée ? Non toxique ? Coût acceptable ? Effets secondaires restreints ? Résistance bactérienne ?

4. Prophylaxie : limiter la résistance bactérienne Traiter un grand nombre de patients sains ? La prophylaxie n’est pas le curatif Posologie moindre Durée courte Voie adaptée Pas de molécule de réserve Spectre ciblé

5. Antibioprophylaxie pour : Tuer les bactéries de surface Collyre Systémique Tuer les bactéries qui ont pénétré dans l’oeil Intraoculaire Systémique Collyre

6. Antibioprophylaxie • Chirurgie à globe ouvert Cataracte • Injections intravitréennes

7. Dans le monde …

8.  Les références en France SFAR 1999 FQ orale si diabétique ou implant 2aire ESCRS 2005 FQ topique péri-op + céfuroxime en CA Etude ESCRS 2007 ? Reco AFSSAPS ???

9. Prophylaxis of postoperative endophthalmitis following cataract surgery : results of the ESCRS multicenter study and identification of risk factorsESCRS Endophthalmitis Study GroupJournal of Cataract & Refractive Surgery33, 6, 978-988 (June 2007)

10. Antibiotique en CA 1 mg céfuroxime 0.26% (22 091) ? 0.06% (118 151) par 4.3 Montan P, Ophthalmology 1998 Montan P, J Catatact Refract Surg 2002 Intracameral injection has been tested. Per Montan was the first to report a 4fold decrease in the incidence of endophthalmitis When usingf intracameral cefuroxime.Intracameral injection has been tested. Per Montan was the first to report a 4fold decrease in the incidence of endophthalmitis When usingf intracameral cefuroxime.

11. Céfazoline en CA 2.5 mg , 18 579 cataractes 0.42% ? 0.04% : par 9 Garat M, J Cataract Refract Surg 2009, 35, 637-42 1 mg , 7 268 cataractes 0.63% ? 0.05% : par 12 Romero P, J Cataract Refract Surg 2006, 32, 438-41 Retrospective observational high effective studies from Spain reported a ten-fold decrease when intracameral cefazolin was injected.Retrospective observational high effective studies from Spain reported a ten-fold decrease when intracameral cefazolin was injected.

12. Céfuroxime efficace : OR = 4.92 The study was stopped at the intermediate analysis due to significant results: cefuroxime reduced the risk of postoperative endopthalmitis by a factor 5. This first prospective large study with cefuroxime and the spanish studies with cefazolin show a significant effect of intracameral antibiotics, without toxicity in large populations. Therefore, as the risk of inducing resistance to last-line antibiotics is low when using in situ first or second generation cephalosporin, Might we give systematically intracameral antibioprohylaxis in every cataract surgery ? Except if history of allergy to penicillin, of course.The study was stopped at the intermediate analysis due to significant results: cefuroxime reduced the risk of postoperative endopthalmitis by a factor 5. This first prospective large study with cefuroxime and the spanish studies with cefazolin show a significant effect of intracameral antibiotics, without toxicity in large populations. Therefore, as the risk of inducing resistance to last-line antibiotics is low when using in situ first or second generation cephalosporin, Might we give systematically intracameral antibioprohylaxis in every cataract surgery ? Except if history of allergy to penicillin, of course.

13. Céfuroxime : pas de préparation commerciale adaptée Reconstitution à partir des flacons pour IV 250 mg, 750 mg, 1500 mg

14. Céfuroxime : pas de préparation commerciale adaptée Préparé par la pharmacie, puis stocké Au réfrigérateur qq jours Das Gupta 86, Galanti 96 Au congélateur qq mois Hecq 05 Extemporané au bloc 2 dilutions Risques : Erreurs de dilution Contamination

15. Antibioprophylaxie cataracte

16. Antibioprophylaxie

17. Si allergie aux bétalactamines ? si FR : lévofloxacine PO veille + jour ? si pas de FR : rien

18. Fluoroquinolones orales mg/ml Moxiflo Gatiflo Lévoflo Oflo Cipro ------------------------------------------------------------------------------ [C] Vitré 1.34 1.34 2.39 0.43 0.56 ------------------------------------------------------------------------------ CMI90 Staph epi 0.13 0.25 0.50 0.50 1.00 Staph aur 0.06 0.13 0.25 0.50 0.50 Strepto 0.25 0.50 1.00 2.00 1.00 ----------------------------------------------------------------------------- ? Pas d’étude dans la prophylaxie ? Sélection de résistants ? Kinetic studies have shown significant intraocular penetration of fluoroquinolones, usually after the administration of two tablets, the balance concentration/ MICs is favorable. Regarding the Gram positive organisms, moxifloxacin and gatifloxacin appear to be the most promising, with a better penetration of moxifloxacin in the aqueous. But untill now, we do not know if this difference is clinically relevant. Please remeber that only ciprofloxacin is effective against Pseudomonas aeruginosa. Kinetic studies have shown significant intraocular penetration of fluoroquinolones, usually after the administration of two tablets, the balance concentration/ MICs is favorable. Regarding the Gram positive organisms, moxifloxacin and gatifloxacin appear to be the most promising, with a better penetration of moxifloxacin in the aqueous. But untill now, we do not know if this difference is clinically relevant. Please remeber that only ciprofloxacin is effective against Pseudomonas aeruginosa.

19. Facteurs de risque Diabète déséquilibré Immunodépression Corticothérapie systémique Infection actuelle Implantation de DM intraoculaire Implantation 2aire, EIC

20. Cas particuliers Patient ayant déjà fait une endophtalmie Monophtalme

21. Rupture capsulaire, issue de vitré Lévofloxacine 500 mg IV Céfuroxime en CA …??

22. Céfu en UKGore, J Cataract Refract Surg 09 55% des chirurgiens répondeurs 48% ont switché après l’ESCRS study 19% vont le faire 76% par décision de service 67% tiennent pas compte de l’allergie

23. Faut-il une antibioprophylaxie collyre pré-opératoire ? ? Effet additionnel / Bétadine® ? The aim of preoperative topical antibiotics is to reduce the number of pathogens on the ocular surface. It is the same goal than antiseptics. Actually: mainly fluroroquinolones, are applied in various way. The aim of preoperative topical antibiotics is to reduce the number of pathogens on the ocular surface. It is the same goal than antiseptics. Actually: mainly fluroroquinolones, are applied in various way.

24. Prophylaxis of postoperative endophthalmitis following cataract surgery : results of the ESCRS multicenter study and identification of risk factorsESCRS Endophthalmitis Study GroupJournal of Cataract & Refractive Surgery33, 6, 978-988 (June 2007)

25. Lévoflo collyre pré-op inefficace The study was stopped at the intermediate analysis due to significant results: cefuroxime reduced the risk of postoperative endopthalmitis by a factor 5. This first prospective large study with cefuroxime and the spanish studies with cefazolin show a significant effect of intracameral antibiotics, without toxicity in large populations. Therefore, as the risk of inducing resistance to last-line antibiotics is low when using in situ first or second generation cephalosporin, Might we give systematically intracameral antibioprohylaxis in every cataract surgery ? Except if history of allergy to penicillin, of course.The study was stopped at the intermediate analysis due to significant results: cefuroxime reduced the risk of postoperative endopthalmitis by a factor 5. This first prospective large study with cefuroxime and the spanish studies with cefazolin show a significant effect of intracameral antibiotics, without toxicity in large populations. Therefore, as the risk of inducing resistance to last-line antibiotics is low when using in situ first or second generation cephalosporin, Might we give systematically intracameral antibioprohylaxis in every cataract surgery ? Except if history of allergy to penicillin, of course.

26. Faut il une antibioprophylaxie collyre pré-opératoire ? Non, si on utilise la Bétadine® The aim of preoperative topical antibiotics is to reduce the number of pathogens on the ocular surface. It is the same goal than antiseptics. Actually: mainly fluroroquinolones, are applied in various way. The aim of preoperative topical antibiotics is to reduce the number of pathogens on the ocular surface. It is the same goal than antiseptics. Actually: mainly fluroroquinolones, are applied in various way.

27. Faut il une antibioprophylaxie collyre post-opératoire ? Oui, jusqu’à étanchéité des incisions Consensus professionnel

28. Antibioprophylaxie cataracte

29. Antibioprophylaxie cataracte

30. Autres chirurgies à globe ouvert Si facteurs de risque : FQ orale Céfuroxime en CA pour le SA…? Collyre antibiotique post-op

31. Chirurgie réfractive Collyre antibiotique post-op LASIK : antibiothérapie pré-op

32. PCA, ponctions DR Collyre antibiotique post-op

33. Antibioprophylaxie • Chirurgies à globe ouvert Cataracte • Injections intravitréennes (IVT)

34. IVT: geste effractif et répété Recommandations AFSSAPS pour Macugen® « A ce jour, il n’y a pas de preuve scientifique établie de l’intérêt d’une antibiothérapie en pré-opératoire. » RCP Macugen ® et Lucentis ® « Antibactérien avant et après » Linezolidt is the first drug of a new family the oxazolidinone. It has a broad spectrum activity against Gram positive bacteria which are the most frequent cause of postoperative endophthalmitis. When given a single oral 600 mg of linezolid, the concentrations achieved in the aqueous exceed the MICs of Gram positive bacteria for at least 12 hours. In the vitreous, its penetration is lower and delayed. Unfortunately, linezolid might not be a good choice in ophthamology since toxic optic neuropathy has been reported in long term treatment , requiring withdrawal of the antibiotic to recover visual function. Anywhere, it has not been tested in endophthalmitis.Linezolidt is the first drug of a new family the oxazolidinone. It has a broad spectrum activity against Gram positive bacteria which are the most frequent cause of postoperative endophthalmitis. When given a single oral 600 mg of linezolid, the concentrations achieved in the aqueous exceed the MICs of Gram positive bacteria for at least 12 hours. In the vitreous, its penetration is lower and delayed. Unfortunately, linezolid might not be a good choice in ophthamology since toxic optic neuropathy has been reported in long term treatment , requiring withdrawal of the antibiotic to recover visual function. Anywhere, it has not been tested in endophthalmitis.

35. IVT Macugen® : endophtalmies % Nb inj --------------------------------------------------------------- Cunningham 0.15% 4 091 Ophthalmology 05 VISION group 0.18% 7 171 Ophthalmology 06 VISION group 0.04% 4 465 Ophthalmology 06 --------------------------------------------------------------- ? Conditions chirurgicales + ATB topiques péri-op Fluoroquinolones have a favorable kinetics with - A good oral absorption, of quite 90%, allowing an oral administration - Long serum elimination half lives that allow once or twice daily dosing - And relativelly low incidence of serious side effects.Fluoroquinolones have a favorable kinetics with - A good oral absorption, of quite 90%, allowing an oral administration - Long serum elimination half lives that allow once or twice daily dosing - And relativelly low incidence of serious side effects.

36. IVT Lucentis® : endophtalmie % Nb inj ------------------------------------------------------------- Rosenfeld 0.06% 8 592 N Engl J Med 06 Brown 0.05% 5 921 Ophthalmology 09 ------------------------------------------------------------- RCP (AMM) : Conditions chirurgicales + ATB topiques péri-op Fluoroquinolones have a favorable kinetics with - A good oral absorption, of quite 90%, allowing an oral administration - Long serum elimination half lives that allow once or twice daily dosing - And relativelly low incidence of serious side effects.Fluoroquinolones have a favorable kinetics with - A good oral absorption, of quite 90%, allowing an oral administration - Long serum elimination half lives that allow once or twice daily dosing - And relativelly low incidence of serious side effects.

37. IVT = quel antibiotique ? FQ = non ? à réserver pour le curatif des pathologies sévères Aminosides Acide fusidique Rifamycine Azithromycine Linezolidt is the first drug of a new family the oxazolidinone. It has a broad spectrum activity against Gram positive bacteria which are the most frequent cause of postoperative endophthalmitis. When given a single oral 600 mg of linezolid, the concentrations achieved in the aqueous exceed the MICs of Gram positive bacteria for at least 12 hours. In the vitreous, its penetration is lower and delayed. Unfortunately, linezolid might not be a good choice in ophthamology since toxic optic neuropathy has been reported in long term treatment , requiring withdrawal of the antibiotic to recover visual function. Anywhere, it has not been tested in endophthalmitis.Linezolidt is the first drug of a new family the oxazolidinone. It has a broad spectrum activity against Gram positive bacteria which are the most frequent cause of postoperative endophthalmitis. When given a single oral 600 mg of linezolid, the concentrations achieved in the aqueous exceed the MICs of Gram positive bacteria for at least 12 hours. In the vitreous, its penetration is lower and delayed. Unfortunately, linezolid might not be a good choice in ophthamology since toxic optic neuropathy has been reported in long term treatment , requiring withdrawal of the antibiotic to recover visual function. Anywhere, it has not been tested in endophthalmitis.

38. Prophylaxie « durable »: limiter la résistance bactérienne La prophylaxie n’est pas le curatif Posologie moindre Durée courte Voie adaptée Pas de molécule de réserve Spectre ciblé

39. Antibioprophylaxie • Cataracte, segment antérieur ? Intracamérulaire + collyre post-op • Autres chirurgies à globe ouvert ? FQ orale si FR + collyre post-op • Injections intravitréennes ? Collyre péri-op

40. Antibioprophylaxie Raisonnée pour être durable Locale ++ En attente de recommandations …