ICAAC/RICAI 2008 Nouveaux antibiotiques

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ICAAC/RICAI 2008 Nouveaux antibiotiques. T Doco-Lecompte. Doripnme. Pharmacologie. Carbapnme injectable Spectre large Stable en prsence de lactamases 500 mg x 3/j IV. T. R. FRITSCHE ; ICAAC 2006. 5298 souches au Canada. DJ Hoban ; ICAAC 2008. - PowerPoint PPT Presentation

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  • ICAAC/RICAI 2008 Nouveaux antibiotiquesT Doco-Lecompte

  • Doripnme

  • PharmacologieCarbapnme injectableSpectre largeStable en prsence de lactamases 500 mg x 3/j IV

  • T. R. FRITSCHE ; ICAAC 2006

    Organism (no. tested)MIC (g/ml)

    50%90%S. aureus (OXA-S; 7,621)0.060.06CoNS* (OXA-S; 816)0.060.06BHS* (1,336)0.060.06S. pneumoniae; (3,554)0.060.5H. influenzae (2,985)0.060.25E. coli (EC; 8,528)0.060.06Klebsiella spp. (3,837)0.060.06Enterobacter spp. (2,211)0.060.12P. aeruginosa (3,874)0.58Acinetobacter spp. (1,204)1>8

  • DJ Hoban ; ICAAC 20085298 souches au Canada

    Drug (MIC90 g/ml)DoripenemMeropenemErtapenemE. coli (1701)0.120.120.06P. aeruginosa (633)8832K. pneumoniae (455)0.120.120.06E. cloacae (166)0.120.120.5S. aureus (MS) (1088)0.120.120.25HA-MRSA (285)32>32>32CA-MRSA (71)244S. pneumoniae (ALL) (654)0.060.060.06E. faecalis (154)8816E. faecium (58)>64>64>32

  • Comparison of In Vitro Activity of Doripenem and Imipenem Against Pseudomonas aeruginosa Using Etest - The 2007-2008 CASTLE StudyR. BADAL ICAAC 2008

    Of 3,234 PA isolates 81.9% were susceptible (S) to DOR and 78.1% to IPM. MIC50/90 for DOR and IPM were 0.25/8 and 2/>32, respectively. Of 2,524 IPM-S strains, 2468 (97.8%) were DOR-S. 180 of 710 (25.4%) IPM non-susceptible strains were DOR-S (62/104 IPM-I strains, and 118/606 IPM-R strains). Conversely, of 586 strains above the DOR S breakpoint of 2mcg/ml, only 9.6% were IPM-S (4mcg/mL). Conclusions: DORs MIC50 and MIC90 were 8-fol d and 8-fold, respectively, lower than IPMs against PA (0.25/8 mcg/mL for DOR vs 2/>32 mcg/mL for IPM). IPM susceptibility can be used to predict DOR susceptibility with a 98% correlation.With just over 25% of IMP-R PA (MIC 8 mcg/mL) remaining susceptible to DOR (MIC 2 mcg/mL), these data support the observation that DOR has higher in vitro activity against PA than IPM.

  • In Vitro Antibacterial Activity of Doripenem (DOR) Against Hospital Isolates: Proposal for Zone Diameter Breakpoints: A French Multicenter StudyC. LASCOLS. ICAAC 2008

  • AMMAMM en procdure europenne centralise obtenue en septembre 2008Infections intra abdominales compliquesPneumonie de ranimation sous ventilationInfections urinaires compliques

  • Place du doripnme (Plsiat, Montravers, Chastre RICAI 2008)Sur P aeruginosa : Dori > Mro>Imisur Acinetobacter : Dori > MroSur SAMS : Dori = Mro=ImiMoindre risque de slection de Pyo rsistantsToxicit neurologique < ImipnmeStabilit du produit => perfusion prolonge sur 4h possible

  • Ceftobiprole(BAL 9141)Prodrogue : ceftobiprole medocaril (BAL 5788)

  • Spectre Cphalosporine large spectre, voie IVGram +, Gram-Activit bactricide sur Gram + rsistant aux lactamines : SAMR, S pneumoniae rsistant pnicillines et C3GActivit sur entrobactries BLSE et P aeruginosa

  • Mode actionLiaison PBP2 de S aureusLiaison forte et stableBase molculaire de lactivit contre SAMR

  • Pharmacocintique Prodrogue medocaril rapidement convertie en compos actifParamtre PK +++ : Temps au-dessus de la CMI Administration doses multiples : augmentation linaire des AUC et CmaxPas daccumulation Excrtion sous forme inchange dans les urines

  • In Vitro Antibacterial Activity of Ceftobiprole (BPR) Against Hospital Isolates: Proposal for Zone Diameter Breakpoints: A French Multicenter StudyC. LASCOLS. ICAAC 2008

  • Efficacit clinique les infections des tissus cutans et sous cutans y compris pieds diabtiques sans ostite 500 mg/8h perfusion IV 60 mn vs vancomycine 1g/12h + ceftazidime 1g/8h

    BPR (n)VAN + CAZ95% CIClinically Evaluable90.5% (485)90.2% (244)-4.2%, 4.9%Intent-to-Treat81.9% (547)80.8% (281)-4.5%, 6.7%Microbiologically Evaluable90.8% (391)90.5% (199)-4.6%, 5.3%RS Srauss, ICAAC 2007, L-1145Abandon indication pneumonies

  • Telavancine

  • PharmacologieDriv synthtique de la vancomycine : lipoglycopeptide par voie IV exclusiveUne perfusion journalireDose dquilibre partir de la 3me injectionFaible volume de distributionLiaison protines : 90%Elimination : rnale sous forme inchange

  • SpectreGram positif : Entrocoques : E faecium, E faecalis Vanco SStaphylocoques : S aureus y compris SAMRStreptocoquesEspces rsistantes : Gram ngatif

  • Infections des parties molles et des tissus sous cutansEfficacy of Telavancin for Treatment of Surgical Site Infections, S.E Wilson, ICAAC 2007Treatment ClinicalCure, Pathogen Eradication, N (%) N (%) TLV SA 41 (85) 40 (83) VAN SA 33 (70) 30 (64) TLV MRSA18 (86)17 (81) VAN MRSA15 (71)12 (57)

    ICAAC 2008 : 20 abstracts

  • AMMDpt dun dossier de demande dAMM en procdure europenne centraliseInfections compliques de la peau et des tissus mous chez ladulteEtudes en cours : pneumonie dorigine nosocomiale

    Abandon dAMM nphrotoxicit

  • Dalbavancine

  • LipoglycopeptideDriv de la teicoplaninePharmacocintique +++Perfusion IV 500 mg x 2 une semaine dintervalleInfections compliques, peau et tissus mous

  • 9 septembre 2008 : Swissinfo Pfizer retire la demande d'autorisation d'un antibiotique dermatologique New York (AWP/AFX) - Le laboratoire pharmaceutique amricain Pfizer a annonc mardi qu'il retirait ses demandes d'autorisation de mise sur le march aux Etats-Unis et en Europe d'un antibiotique efficace notamment contre le staphylocoque dor, la Dalbavancine, pour de nouvelles exprimentations.

  • Daptomycine + Rifampicinevs Vancomycine: OMA SARM du lapinM. Lefebvre ICAAC 2008

  • Sulopenem (carbapenem oral)M. D. Huband ICAAC 2008

    MICs (g/mL)Organisms (# Tested)RangeMIC50MIC90Staphylococcus aureus MSSA(19)0.06-0.1250.060.125Streptococcus pneumoniae* (114) 0.008-10.060.5S. pyogenes (28)0.015-0.250.030.03S. agalactiae (21)0.03-0.250.060.125Listeria monocytogenes (10)0.06-0.1250.060.125Enterobacteriaceae (200)0.015-640.1251E. coli ESBL+ (17)0.015-0.250.030.125K. pneumoniae ESBL+ (15)0.03-0.50.060.25Moraxella catarrhalis (30)0.008-0.250.0150.25Haemophilus influenzae (65)0.06-10.1250.5

  • Assessment of the In Vivo Activity of Ceftaroline (CPT) Against Vancomycin-Susceptible and -Resistant Enterococcus faecalis (EF) Strains in a Rabbit Endocarditis Model (REM): Comparison with Linezolid (LZO) and Vancomycin (VAN)C. JACQUELINE. ICAAC 2008Gram + (SAMR, PSDP, certains Gram -)

  • AutresPyrrolamides : inhibiteurs de la DNA gyrase, sous unit B Novel bis-(imidazolinylindole) Antibacterials Active Against a Broad Spectrum of BacteriaThe Enoyl-ACP reductase FabI which catalyzes the final step of bacterial fatty elongation cycle is a very attractive target for new antibacterial drug discovery : aryloxy phenol, inhibiteur de Fab1 : MUT37307 (antistaph)