ENDOFTALMITI POSTCHIRURGICHE

Transcript

1 ENDOFTALMITI POSTCHIRURGICHE quadri clinici, prevenzione, diagnosi e trattamento Giacomo Savini Piero Barboni Michele Carbonelli Marco Deluigi Bologna, 5 Novembre 2009 con la collaborazione di

2 DIAGNOSI E TERAPIA Piero Barboni

3 Analisi microbiologiche Prima del trattamento Tampone congiuntivale Prelievo endoculare: acqueo e vitreo Aspirazione da C.A. Siringa 1cc con Ago 27/30 Ga Aspirare 0,2 cc di acqueo

4 Analisi microbiologiche Prima del trattamento Tampone congiuntivale Prelievo endoculare: acqueo e vitreo Aspirazione Vitreo Prelevare 0,2 cc di vitreo via pars plana (prima dell iniezione o della vitrectomia) Ago 23 Ga oppure vitrectomo collegati a siringa 1-5 cc

5 Analisi microbiologiche Come trasportare il campione? Contenitori sterili con agar gel (mantiene i microorganismi x 24 ore) ago lungo per terreno (spinale)

6 Analisi microbiologiche Dove? Microbiologia S.Orsola (Clinica Medica Vecchia, Batteriologia 2 piano, tel / ) I campioni vanno portati al Laborat. Prelievi (via Palagi 9, piano seminterrato, sportello 6 - Libera Professione) dalle 7.15 alle 10.45

7 Analisi microbiologiche Dove? Sala operatoria Villa Laura Accordo diretto con Microbiologia S.Orsola

8 Analisi microbiologiche cosa? Colorazione Gram Coltura (aerobi, anaerobi, funghi) Antibiogramma crescita 24h 48h...

9 Analisi microbiologiche significato? aggiustamento terapeutico epidemiologico medico legale

10 TERAPIA Endophtalmitis Vitrectomy Study Group 1995 tutti Antibiotici intravitreali (vancomicina+amikacina) Sottocongiuntivale (vancom.+ceftazidima+desam.) Antibiotici topici randomizzati Antibiotici EV (ceftazidima+amikacina) Vitrectomia

11 TERAPIA Antibiotici intravitreali Vitrectomia Antibiotici sistemici

12 TERAPIA Nessun antibiotico attivo al 100% su tutti i batteri (Gram +/-) GRAM + Vancomicina: 100% Gentamicina: 78,4% Ciprofloxacina: 68,3% Cefazolina: 66,8% Ceftazidima: 63,6% 278 endoftalmiti (Bascom Palmer) tra il 1996 ed il 2001 Benz et al. AJO 2004

13 TERAPIA Nessun antibiotico attivo al 100% su tutti i batteri GRAM - Ciprofloxacina: 94,2% (mai usata) Amikacina: 81% Ceftazidima: 80% Gentamicina: 75% Benz et al. AJO 2004

14 TERAPIA Nessun antibiotico attivo al 100% su tutti i batteri Vitreous Isolates Percent Sensitive BPEI N* Cefazolin Ciprofloxacin Amikacin Ceftazidime Gentamicin Vancomycin Levofloxacin Staphylococcus epidermidis Streptococcus viridans grp Coagulase-negative Staphylococcus (other) Staphylococcus aureus Gram-negative rods (other) Enterococcus species Fastidious gram-negative rods Aerobic gram-positive rods Streptococcus pneumoniae Streptococcus (other) Pseudomonas aeruginosa All vitreous isolates (excluding fungi) BPEI Bascom Palmer Eye Institute. *Number of isolates evaluated. Levofloxacin tested mid Not tested. Only gram-positive isolates tested. Benz et al. AJO 2004

17 TERAPIA INIEZIONI INTRAVITREALI Vancomicina (1mg) Amikacina (0,4mg) o Ceftazidima (2,25mg) rischio infarto macula precipita (?) nel vitreo se inoculata insieme a vanco

18 TERAPIA VANCOMICINA glicopeptide Gram + Fascia H Vancomicina A.P. 500 mg (Eli Lilly Italia) Vancomicina HKM 500 mg (Hikma Italia) Vancomicina Hosp. 500 mg (Hospira) Vancotex 500 mg (Pharmatex Italia) Zengag 500 mg (Fisiopharma) Attiva sul 100% dei Gram +

19 TERAPIA Flacone 500 mg Vancomicina Diluire con 100 cc soluz. fisiologica Diluire con 50 cc soluz. fisiologica 500 mg / 100 cc = 5 mg /cc 500 mg / 50 cc = 10 mg /cc Iniettare 1 mg / 0.2 cc Iniettare 1 mg / 0.1 cc

20 TERAPIA Flacone 500 mg Vancomicina Diluire con 100 cc soluz. fisiologica Diluire con 50 cc soluz. fisiologica 500 mg / 100 cc = 5 mg /cc 500 mg / 50 cc = 10 mg /cc Iniettare 1 mg / 0.2 cc Iniettare 1 mg / 0.1 cc No tossicità dopo iniezione di 5mg in CA (Fry. JCRS 2005)

21 TERAPIA CEFTAZIDIMA cefalosporina Glazidim 1fiala IM 1g + 1 fiala Gram +/- solvente 3ml (Glaxosmithkline) Fascia H (EV) o A (IM) iniez. vanco separata? Mantiene attività antibat. anche se iniettata insieme a vanco (Raju et al. Retina 2008) Attiva sul 100% dei Gram - (Recchia et al. Arch Ophthalmol 2005) Attiva sull 89% dei Gram - (EVS. Arch Ophthalmol 1996) Attiva sull 63,6% dei Gram + (Benz AJO 2004)

22 TERAPIA Flacone 1000 mg Ceftazidima Diluire con 100 cc soluz. fisiologica 1000 mg / 100 cc = 10 mg /cc Iniettare 2 mg / 0.2 cc Diluire con 50 cc soluz. fisiologica 1000 mg / 50 cc = 20 mg /cc Iniettare 2 mg / 0.1 cc

23 TERAPIA AMIKACINA aminoglicoside inibiscono sintesi proteica ribosomi batterici simili a quelli mitocondriali cross reazione varianti di sequenza mito piu simili a quelli batterici tossicita iatrogena sordita e cecita Gram +/- Fascia A BB-K8 500mg/2ml (Bristol-Myers Squibb) Attiva sull 89% dei Gram - (EVS. Arch Ophthalmol 1996) Sinergia con vanco nell azione su Gram + Rischio infarto maculare (molto basso: 1/420 occhi EVS) Galloway et al. BJO 2002

24 TERAPIA AMIKACINA aminoglicoside Inibitori della sintesi proteica ribosomi batterici inibiscono sintesi proteica ribosomi batterici simili a quelli mitocondriali cross reazione varianti di sequenza mito piu simili a quelli batterici tossicita iatrogena sordita e cecita somiglianza con ribo mitocondriali cross reazione tossicità iatrogena (nervo ottico e nervo acustico) Figure 1 Fundus photograph showing diffuse posterior pole retinal cloudy swelling, cotton wool spots, and scattered intraretinal haemorrhages. Figure 2 Fluorescein angiogram at 48 seconds showing diffuse macular arteriolar occlusion with staining of the arteriolar walls along the inferior and superior arcades. Galloway et al. BJO 2002

25 TERAPIA Flacone 500 mg Amikacina 500 mg / 2 cc = 400 mg /1,6 cc Diluire con 2 cc soluz. fisiologica portare a 100 cc soluz. fisiologica 400 mg / 100 cc = 4 mg / cc Iniettare 0,4 mg / 0,1 cc

26 Kit di EMERGENZA Vancomicina 1 confezione 500 mg 1 soluz. fisiologica 50ml (100 ml) Ceftazidima 1 confezione 1000 mg 1 soluz. fisiologica 50ml (100 ml) Amikacina 1 confezione 500 mg 1 soluz. fisiologica 100 ml

27 TERAPIA Desametazone Riduce il danno causato dalle tossine batteriche e dalla risposta infiammatoria Pochi studi su uomini Risultati contrastanti Effetto positivo (Gan et al. Graefe s 2005, Das et al BJO 1999) Effetto negativo (Shah et al. Ophthalmology 2000) 0,4 mg/0,1 ml

28 TERAPIA Decadron 4 mg (Desameta FOS 4 mg) Diluire con 1 cc soluz. fisiologica Iniettare 0,4 mg / 0,1 cc

29 TERAPIA VITRECTOMIA Protocolli EVS (randomizzazione) Indicata solo per pz con visus percezione luce Tutti i pz. diabetici (anche con visus > moto mano)

30 TERAPIA Vitrectomia (EVS) Limitazioni chirurgiche per paura distacco di retina iatrogeno Solo core vitrectomy (mantenere almeno il 50% del vitreo) No distacco ialoide posteriore

31 TERAPIA Vitrectomia (EVS) Limitazioni chirurgiche per paura distacco di retina iatrogeno Solo core vitrectomy (mantenere almeno il 50% del vitreo) No distacco ialoide posteriore Persistenza elevate quantità materiale infetto nella cavità vitreale

32 TERAPIA Vitrectomia: sono ancora valide le indicazioni dell EVS? Graefe s Arch Clin Exp Ophthalmol (2005) 243: EDITORIA L DOI /s Ferenc Kuhn Giampaolo Gini Ten years after... are findings of the Endophthalmitis Vitrectomy Study still relevant today?

33 Vitrectomia TERAPIA Dobbiamo avere paura del distacco? Nell EVS rischio di distacco 260% più alto nei non vitrectomizzati Alterazioni macula da distacco meno importanti di alterazioni da endoftalmite Possibilità di usare olio di silicone

34 TERAPIA Vitrectomia Dobbiamo avere paura del distacco? Evoluzione tecnologica vitrectomi Miglioramento sistemi di visione

35 TERAPIA Vitrectomia Dobbiamo avere paura del distacco? Evoluzione tecnologica vitrectomi Miglioramento sistemi di visione Minore rischio nell effettuare vitrectomia totale e indurre distacco posteriore ialoide

36 TERAPIA Vitrectomia: razionale Eliminare TUTTI gli agenti dannosi dalla cavità vitreale PRIMA che l acuità visiva si deteriori fino a percezione luce e che il danno sia irreversibile E fondamentale intervento PRECOCE Kuhn et al. Graefe s Arch Ophthalmol 2005

37 TERAPIA Vitrectomia: indicazioni Tutti i casi di endoftalmite avanzata Tutti i casi che non migliorano entro 24 ore dall iniezione intravitreale di antibiotici Kuhn et al. Graefe s Arch Ophthalmol 2005

38 Vitrectomia TERAPIA Verosimile utilità anche nei casi con visus percezione luminosa IntraOcular Antibiotic Injection Altan et al. Retina 2009

39 Vitrectomia TERAPIA Verosimile utilità anche nei casi con visus > percezione luminosa 91% degli occhi con visus finale > 5/10 (53 % nell EVS) Kuhn et al. Graefe s Arch Ophthalmol 2005

40 TERAPIA Vitrectomia: tecnica Lavaggio C.A. Pulizia superficie IOL Capsulectomia posteriore x irrigare il sacco capsulare Vitrectomia totale Distacco ialoide (macula)

41 TERAPIA Quando eseguire seconda procedura? In assenza di miglioramento: 24 ore (Kuhn et al. Graefe s Arch Ophthalmol 2005) 60 ore (Altan et al. Retina 2009)

42 TERAPIA SISTEMICA Protocolli EVS (randomizzazione) Ceftazidima + Amikacina endovena No Vancomicina (scarsa penetrazione intraoculare) NO BENEFICIO ANTIBIOTICI E.V. Gram+ Vancomicina: 100% Gentamicina: 78,4% Ciprofloxacina: 68,3% Cefazolina: 66,8% Ceftazidima: 63,6%

43 TERAPIA SISTEMICA Svantaggi Antibiotici E.V. Rischio effetti collaterali sistemici Necessità ospedalizzazione Costo Limite EVS: antibiotici di vecchia generazione che non oltrepassano la barriera emato-retinica El-Massry et al. AJO 1996 Aguilar et al. Retina 1995

44 TERAPIA SISTEMICA Pochi antibiotici penetrano la barriera emato-retinica Levofloxacina, moxifloxacina e gatifloxacina Linezolid Aminoglicosidi e vancomicina non penetrano nel vitreo

45 TERAPIA SISTEMICA Risultati diversi con ANTIBIOTICI x OS Associati ad una migliore prognosi visiva

46 TERAPIA SISTEMICA Risultati diversi con ANTIBIOTICI x OS Management and Outcomes of Postoperative Endophthalmitis since the Endophthalmitis Vitrectomy Study The Endophthalmitis Population Study of Western Australia (EPSWA) s Fifth Report Jonathon Q. Ng, MBBS, BA, 1 Nigel Morlet, FRACS, FRANZCO, 2 John W. Pearman, MD, FRCPA, 3 Ian J. Constable, FRACS, FRANZCO, 4,5 Ian L. McAllister, FRACS, FRANZCO, 2,4 Christopher J. Kennedy, PhD, FRANZCO, 6 Timothy Isaacs, FRANZCO, 2,4 James B. Semmens, MSc, PhD, 1 for Team EPSWA* Purpose: To examine if changes in the diagnosis and management of postoperative endophthalmitis have occurred since 1995, and to identify factors that might predict final visual outcome. Design: Retrospective, population-based, noncomparative, consecutive case series. Participants: Patients with clinically diagnosed endophthalmitis after cataract surgery and lens-related surgery in Western Australia from 1980 to Methods: Endophthalmitis cases were identified using record linkage and cross-referencing with the surgical logbooks of vitreoretinal surgeons before validation by medical record review. Main Outcome Measures: Microbiological data (microorganisms isolated and antibiotic susceptibilities), diagnostic interventions, surgical procedures, therapeutic interventions, and visual acuity (VA). Results: During the 21-year period, 213 episodes of endophthalmitis occurred after cataract surgery. Since 1995, both anterior chamber sampling and vitreous sampling have increased significantly. The overall use of vitrectomy has also increased, but we did not observe a difference according to presenting VA. Intravitreal antibiotic use increased significantly, whereas the use of both subconjunctival and IV antibiotics decreased. In one third of patients, the VA at least 6 months after admission for endophthalmitis was worse than 6/18. This was associated with treatment that did not include the use of oral antibiotics (odds ratio [OR], 3.86; 95% confidence interval [CI], ; P 0.02), growth from intraocular samples of organisms other than coagulase-negative staphylococci (OR, 9.84; 95% CI, ; P 0.001), and a discharge VA worse than 6/18 (OR, 6.10; 95% CI, ; P 0.01). Conclusions: Although we observed noticeable changes in the diagnosis and management of endophthalmitis since 1995, visual outcomes have not improved and remain poor. Our finding that treatment with oral antibiotics may be associated with a better visual outcome warrants further investigation. Ophthalmology 2005; 112: by the American Academy of Ophthalmology.

47 TERAPIA SISTEMICA Quali antibiotici per via sistemica? LEVOFLOXACINA Buona penetrazione intraoculare

48 TERAPIA SISTEMICA Quali antibiotici per via sistemica? LEVOFLOXACINA Buona penetrazione intraoculare Aqueous and Vitreous Penetration of Levofloxacin after Oral Administration Richard G. Fiscella, RPh, MPH, 1,2 Thao K. P. Nguyen, MD, 2 Michael J. Cwik, PhD, 3 Brian A. Phillpotts, MD, 4 Steven M. Friedlander, MD, 5 Daniel C. Alter, MD, PhD, 2 Michael J. Shapiro, MD, 2 Norman P. Blair, MD, 2 Jon P. Gieser, MD 2 Objective: To investigate the penetration of levofloxacin, an optical S-(-)isomer of ofloxacin, into the aqueous and vitreous humor after oral administration. Design: Randomized, clinical trial comparing tissue levels of levofloxacin after one or two doses 12 hours apart. Participants: Forty-five patients undergoing initial vitrectomy between February 1997 and June 1997 at the UIC Eye Center. Methods: Aqueous, vitreous, and serum samples were obtained and later analyzed from 45 patients after oral administration of mg tablet (group 1, 22 patients) or mg tablets (group 2, 23 patients) 12 hours apart before surgery. Main Outcome Measures: Aqueous, vitreous, and serum concentrations of levofloxacin (micrograms/ milliliter). Results: Group 1 achieved mean aqueous, vitreous, and serum levels of g/ml, g/ml, and g/ml, respectively. Group 2 achieved mean aqueous, vitreous, and serum levels of g/ml, g/ml, and g/ml. Conclusions: Mean inhibitory aqueous and vitreous MIC 90 levels were achieved against a majority of ocular pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae (vitreous), Bacillus cereus (vitreous), Haemophilus influenzae, Moraxella catarrhalis, and most gram-negative aerobic organisms except Pseudomonas aeruginosa after two doses given 12 hours apart. Mean MIC 90 levels were obtained in the vitreous for a majority of pathogens responsible for traumatic, postoperative, or bleb-related endophthalmitis. Ophthalmology 1999;106:

49 TERAPIA SISTEMICA Levofloxacina - Disponibile in Italia: Tavanic 500 mg cpr Priscar 500 mg cpr Levoxacin 500 mg cpr Costo 22 euro (fascia A)

50 TERAPIA SISTEMICA LEVOFLOXACINA 500 mg x2 (a distanza di 12 ore)

51 TERAPIA SISTEMICA LEVOFLOXACINA Resistenza da parte di alcuni Gram+ Vitreous Isolates Percent Sensitive BPEI N* Cefazolin Ciprofloxacin Amikacin Ceftazidime Gentamicin Vancomycin Levofloxacin Staphylococcus epidermidis Streptococcus viridans grp Coagulase-negative Staphylococcus (other) Staphylococcus aureus Gram-negative rods (other) Enterococcus species Fastidious gram-negative rods Aerobic gram-positive rods Streptococcus pneumoniae Streptococcus (other) Pseudomonas aeruginosa All vitreous isolates (excluding fungi) BPEI Bascom Palmer Eye Institute. *Number of isolates evaluated. Levofloxacin tested mid Not tested. Only gram-positive isolates tested. Benz et al. AJO 2004

52 TERAPIA SISTEMICA LEVOFLOXACINA Resistenza da parte di alcuni Gram+ Vitreous Isolates Percent Sensitive BPEI N* Cefazolin Ciprofloxacin Amikacin Ceftazidime Gentamicin Vancomycin Levofloxacin Staphylococcus epidermidis Streptococcus viridans grp Coagulase-negative Staphylococcus (other) Staphylococcus aureus Gram-negative rods (other) Enterococcus species Fastidious gram-negative rods Aerobic gram-positive rods Streptococcus pneumoniae Streptococcus (other) Pseudomonas aeruginosa All vitreous isolates (excluding fungi) BPEI Bascom Palmer Eye Institute. *Number of isolates evaluated. Levofloxacin tested mid Not tested. Only gram-positive isolates tested. Benz et al. AJO 2004

53 TERAPIA SISTEMICA Fluorochinolonici di 4a generazione Gatifloxacina Moxifloxacina Grepafloxacina Trovafloxacina Ampio spettro d azione Gram + e - Batteri atipici (mycoplasma, legionella, chlamydia) Anaerobi (propionibacterium acnes)

54 TERAPIA SISTEMICA GATIFLOXACINA Buona penetrazione intraoculare 400 mg x2 (a distanza di 12 ore) Non disponibile in Italia Hariprasad et al. Arch Ophthalmol 2003

55 TERAPIA SISTEMICA MOXIFLOXACINA Buona penetrazione nel vitreo e nell acqueo 400 mg x2 (a distanza di 12 ore) No effetti collaterali sistemici negli studi effettuati Vedantham et al. Eye 2006 Hariprasad et al. Arch Ophthalmol 2006 Fuller et al. AJO 2007 Lott et al. Retina 2008

56 TERAPIA SISTEMICA MOXIFLOXACINA Ben tollerata in caso di insufficienza renale ed epatica Reazioni avverse più comuni: diarrea e nausea (lievi) Da evitare in pz che usano antiaritmici (amiodarone) Hariprasad et al. Arch Ophthalmol 2006

57 TERAPIA SISTEMICA MOXIFLOXACINA Maggiore spettro d azione rispetto a Levofloxacina Table 1. In Vitro Susceptibilities of Moxifloxacin, Gatifloxacin, Levofloxacin, Ofloxacin, and Ciprofloxacin Showing Minimal Inhibitory Concentration Against 90% of Isolates* Moxifloxacin Gatifloxacin* Levofloxacin* Ofloxacin* Ciprofloxacin* Vitreous penetration, mean ± SD 1.34 ± 0.66 µg/ml 1.34 ± 0.34 µg/ml 2.39 ± 0.70 µg/ml 0.43 ± 0.47 µg/ml 0.56 ± 0.16 µg/ml Gram-positive organisms Staphylococcus epidermidis Staphylococcus aureus (MSSA) Streptococcus pneumoniae Streptococcus pyogenes Bacillus cereus Enterococcus faecalis Gram-negative organisms Proteus mirabilis Pseudomonas aeruginosa Haemophilus influenzae Escherichia coli Klebsiella pneumoniae Neisseria gonorrhoeae Anaerobic organisms Bacteroides fragilis Propionibacterium acnes Abbreviation: MSSA, methicillin-sensitive Staphylococcus aureus. Hariprasad et al. Arch Ophthalmol 2006

58 TERAPIA SISTEMICA MOXIFLOXACINA Maggiore spettro d azione rispetto a Levofloxacina Table 1. In Vitro Susceptibilities of Moxifloxacin, Gatifloxacin, Levofloxacin, Ofloxacin, and Ciprofloxacin Showing Minimal Inhibitory Concentration Against 90% of Isolates* Concentrazione media nell acqueo (1.58µg/mL) superiore alla via topica (ogni 6 ore) Moxifloxacin Gatifloxacin* Levofloxacin* Ofloxacin* Ciprofloxacin* Vitreous penetration, mean ± SD 1.34 ± 0.66 µg/ml 1.34 ± 0.34 µg/ml 2.39 ± 0.70 µg/ml 0.43 ± 0.47 µg/ml 0.56 ± 0.16 µg/ml Gram-positive organisms Staphylococcus epidermidis Staphylococcus aureus (MSSA) Streptococcus pneumoniae Streptococcus pyogenes Bacillus cereus Enterococcus faecalis Gram-negative organisms Proteus mirabilis Pseudomonas aeruginosa Haemophilus influenzae Escherichia coli Klebsiella pneumoniae Neisseria gonorrhoeae Anaerobic organisms Bacteroides fragilis Propionibacterium acnes Abbreviation: MSSA, methicillin-sensitive Staphylococcus aureus. Hariprasad et al. Arch Ophthalmol 2006

59 TERAPIA SISTEMICA MOXIFLOXACINA Maggiore spettro d azione rispetto a Levofloxacina Table 1. In Vitro Susceptibilities of Moxifloxacin, Gatifloxacin, Levofloxacin, Ofloxacin, and Ciprofloxacin Showing Minimal Inhibitory Concentration Against 90% of Isolates* Concentrazione media nell acqueo (1.58µg/mL) superiore alla via topica (ogni 6 ore) Concentrazioni ottenute con 1 cpr la sera prima ed 1 cpr 3 ore prima dell intervento Moxifloxacin Gatifloxacin* Levofloxacin* Ofloxacin* Ciprofloxacin* Vitreous penetration, mean ± SD 1.34 ± 0.66 µg/ml 1.34 ± 0.34 µg/ml 2.39 ± 0.70 µg/ml 0.43 ± 0.47 µg/ml 0.56 ± 0.16 µg/ml Gram-positive organisms Staphylococcus epidermidis Staphylococcus aureus (MSSA) Streptococcus pneumoniae Streptococcus pyogenes Bacillus cereus Enterococcus faecalis Gram-negative organisms Proteus mirabilis Pseudomonas aeruginosa Haemophilus influenzae Escherichia coli Klebsiella pneumoniae Neisseria gonorrhoeae Anaerobic organisms Bacteroides fragilis Propionibacterium acnes Abbreviation: MSSA, methicillin-sensitive Staphylococcus aureus. Hariprasad et al. Arch Ophthalmol 2006

60 TERAPIA SISTEMICA Moxifloxacina - Disponibile in Italia: Actira 400 mg cpr Avalox 400 mg cpr Octegra 400 mg cpr Costo 20 euro (fascia A)

61 TERAPIA SISTEMICA LINEZOLID Buona penetrazione intraoculare

62 TERAPIA SISTEMICA LINEZOLID Buona penetrazione intraoculare Aqueous and Vitreous Penetration of Linezolid (Zyvox) after Oral Administration Richard G. Fiscella, RPh, MPH, 1,2 Wico W. Lai, MD, 2 Bruce Buerk, MD, 2 Mona Khan, MD, 2 Keith A. Rodvold, PharmD, 1 Jose S. Pulido, MD, MS, 2 Sami Labib, RPh, 1 Michael J. Shapiro, MD, 2 Norman P. Blair, MD 2 Objective: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. Design: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). Participants: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. Methods: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. Main Outcome Measures: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). Results: Group 1A achieved mean aqueous, vitreous, and plasma levels of g/ml, g/ml, and g/ml, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of g/ml, g/ml, and g/ml, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of g/ml, g/ml, and g/ml, respectively. Conclusions: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC 90 ) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC 90 were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours. Ophthalmology 2004;111: by the American Academy of Ophthalmology.

63 TERAPIA SISTEMICA LINEZOLID 600 mg x2 (a distanza di 12 ore) Attivo su tutti i Gram + (compresi batteri resistenti alla vancomicina) Concentraz. vitreale entro 4 ore No azione su Gram -

64 TERAPIA SISTEMICA LINEZOLID 600 mg x2 (a distanza di 12 ore) Attivo su tutti i Gram + (compresi batteri resistenti alla vancomicina) Concentraz. vitreale entro 4 ore Tossicità mitocondri con otticopatia se somministrato > 28 gg (analogo cloranfenicolo)

65 TERAPIA SISTEMICA 1 anno terapia 2 settimane sospensione A B C mm S T N I TEMP SUP NAS INF TEMP 217 D mm S N T 203 I TEMP SUP NAS INF TEMP 163 Figure 1 (A) Fundus photographs of our patient on presentation after 1 year of treatment with linezolid. Visual acuity was 20/400 in both eyes. Bilaterally, symmetrical moderate optic disc swelling, optic disc hyperaemia, swelling of the peripapillary retinal nerve fibre layer (PRNFL) and vessel tortuosity are seen. (B) Disc photographs of our patient 2 weeks after discontinuing treatment with linezolid. Visual acuity was 20/25 in both eyes. Bilaterally, a slightly decreased symmetrical optic disc swelling, optic disc hyperaemia, swelling of the PRNFL and vessel tortuosity are seen. Temporal optic disc pallor can be seen bilaterally. (C) PRNFL optical coherence tomography (OCT) of our patient 2 weeks after discontinuing treatment with linezolid showed an increased 360 average measurement ( mm right eye (OD), mm left eye (OS)), with significant increase in thickness detected in the temporal (TEMP), superior (SUP) and inferior (INF) quadrants in both eyes, and in the nasal (NAS) quadrant of the right eye. (D) Disc photographs of our patient 3 months after discontinuing treatment with linezolid. Visual acuity was 20/20 in both eyes. Bilaterally, a marked decrease in symmetrical optic disc swelling, optic disc hyperaemia, swelling of the PRNFL and vessel tortuosity can be seen. Temporal optic disc pallor is still evident bilaterally. (E) PRNFL OCT of our patient 3 months after discontinuing treatment with linezolid, showing a marked decrease in the 360 average measurement ( mm OD, mm OS), with notable decreases in thickness detected in the temporal, superior and inferior quadrants in both eyes, and in the nasal quadrant of the right eye. PERSPECTIVE D E 3 mesi sospensione 121 mm S 65 T N I TEMP SUP NAS INF TEMP 144 Linezolid-induced optic neuropathy: a mitochondrial disorder? M Javaheri, R N Khurana, T M O Hearn, M M Lai, A A Sadun mm S N T 84 I TEMP SUP NAS INF TEMP Br J Ophthalmol 2007;91: doi: /bjo

66 TERAPIA SISTEMICA Linezolid - Disponibile in Italia come: Zyvoxid cpr 600 mg (fascia H) Costa 914 euro!!!

67 TERAPIA SISTEMICA LINEZOLID (600 mg/12 ore) MOXIFLOXACINA (400 mg/12 ore)

68 Ricerca futura Epidemiologia endoftalmiti in Italia Sensibilità flora annessi agli antibiotici topici in commercio in Italia