Nouvelles strateacutegies de prise en charge

Traitements non antibiotiques des infections graves

B Guery (Lille)

1991hellip

51

70 77

43

Placebo n=92HA-1A n=105

laquo We stopped the trial at the first interim analysis because the all-cause mortality rate for patients treated with HA-1A who did not have Gram-negative bacteremia (42 244 of 577) exceeded that of the patients given placebo (38 230 of 608) by an amount greater than that in the prespecified safety stopping rule (F = 009 Fisher one-tailed exact test) raquo

ldquoLenercept had no significant effect on mortality in the study populationrdquo

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

1991hellip

51

70 77

43

Placebo n=92HA-1A n=105

laquo We stopped the trial at the first interim analysis because the all-cause mortality rate for patients treated with HA-1A who did not have Gram-negative bacteremia (42 244 of 577) exceeded that of the patients given placebo (38 230 of 608) by an amount greater than that in the prespecified safety stopping rule (F = 009 Fisher one-tailed exact test) raquo

ldquoLenercept had no significant effect on mortality in the study populationrdquo

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

51

70 77

43

Placebo n=92HA-1A n=105

laquo We stopped the trial at the first interim analysis because the all-cause mortality rate for patients treated with HA-1A who did not have Gram-negative bacteremia (42 244 of 577) exceeded that of the patients given placebo (38 230 of 608) by an amount greater than that in the prespecified safety stopping rule (F = 009 Fisher one-tailed exact test) raquo

ldquoLenercept had no significant effect on mortality in the study populationrdquo

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

laquo We stopped the trial at the first interim analysis because the all-cause mortality rate for patients treated with HA-1A who did not have Gram-negative bacteremia (42 244 of 577) exceeded that of the patients given placebo (38 230 of 608) by an amount greater than that in the prespecified safety stopping rule (F = 009 Fisher one-tailed exact test) raquo

ldquoLenercept had no significant effect on mortality in the study populationrdquo

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

ldquoLenercept had no significant effect on mortality in the study populationrdquo

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

2001hellip

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

NEJM 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

NEJM 2001

Mortaliteacute ndash20

247

308

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

LPS TNF Pas bonhellip

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

ldquoMy approach is nontraditional but from a uniquely Western perspectiverdquo

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

19 patientsgroupGM-CSF (4 mgkgd) or placebo for8 days

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

- 21 patients- Etude prospective

randomiseacutee double aveugle

NS

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

Primary challenge Relapse

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

The combined administration of CDA1 and CDB1 human monoclonal antibodies in addition to antibiotics significantly reduced the recurrence of C difficile infection

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

TTSS a needle

Kubori et al Science 1998

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

Surmortaliteacute et SST III

SSTT [+] SSTT [-]

Mortaliteacute

21 3RR deacutecegraves

PcrV seule 74PcrV + toxine(s)

87(Roy Burman et al J Infect Dis 2001 )(Roy Burman et al J Infect Dis 2001 )

Infection aigueuml

Infection chronique

SSTT [+]

89 41

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

35 patients ventileacutes35 patients ventileacutesPneumonie agrave Pneumonie agrave PaeruginosaPaeruginosa

Production de ProteacuteinesProduction de ProteacuteinesIssues du systegraveme de seacutecreacutetionIssues du systegraveme de seacutecreacutetion

de type III de type III

++27352735

--835835

22 Seacutevegravere22 Seacutevegravere 5 Modeacutereacutees5 Modeacutereacutees 3 Seacutevegraveres3 Seacutevegraveres 5 Modeacutereacutees5 Modeacutereacutees(81)(81) (19)(19) (38)(38) (62)(62)

ExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveresExoU 1035 (29) associeacutee agrave 90 de formes seacutevegraveres

Hauser et al Crit Care Med 2002Hauser et al Crit Care Med 2002

Shime et al J Immunol 2001

Shime et al J Immunol 2001

Membrane disruption and toxin injection into cell

Cell Membrane

Pseudomonas aeruginosa

TTSS

Anti-PcrV Antibody(KB001)

PcrV Protein

ldquoOverall the human monoclonal antibody KBPA-101 was well tolerated over the entire dose range in healthy volunteers and no serious adverse events have been reportedrdquo

KB001 Trial

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

ldquoOverall the human monoclonal antibody KBPA-101 was well tolerated over the entire dose range in healthy volunteers and no serious adverse events have been reportedrdquo

KB001 Trial

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

KB001 Trial

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Chastre et al ATS 2010

Chastre et al ATS 2010

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Chastre et al ATS 2010

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Chastre et al ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

ATS 2010

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

ATS 2010

A Phase III Randomized Double-Blind Placebo-Controlled Single-Dose Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected with Pseudomonas aeruginosaMilla Carlos E Accurso Frank J Chmiel James F McCoy Karen S Billings Joanne L Atkinson Jeffrey J Clancy John P Liou Theodore G Acton James D Lynch Susan V Slusher Nicole A Burns Jane L Mayer-Hamblett Nicole Harris Kirk J Patel Rajesh Tremblay Thomas M Parli Teresa J

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

RhlR RhlI

lasR lasIRsaL

LasILasR

RhlIRhlR

C4

C12

C4

C12

RsaL

PQS

Vfr

QscR

pqsA pqsB pqsC pqsD pqsE

pqsR PqsR

pqsH

VqsR ActivationInhibition

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

QS Inhibition with macrolides

Tateda K et al AAC 2001

Elastase

RhamnolipidNot bactericidalNot bacteriostatic

QS Inhibition

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

no AZM (control)2 gml AZM4 gml AZM8 gml AZM12 gml AZM

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

320 P aeruginosa isolates and tracheal aspirates from 29 patients six developed VAP (20)

7 patients colonized by QS-proficient isolates

57 developed VAP as compared to

22 patients colonized by QS-deficient isolates

9 developed VAP (p = 0018)

Thorax 2010 Aug65(8)703-1

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

- Physicianerythema fraslinflammation ulceration frasl granulation frasl polypsdischarge quantity discharge type and odour

-Patients Discomfort itchiness wetness smell

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

2h pi Preventive 4d

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Microbiote

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Sekirov 2010

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Zoetendal 1998

14 sujets sains

Speacutecifique de chaque individu

Probiotiques Terme introduit en 1953 par Werner

Kollath Par opposition aux antibiotiques Ce sont des facteurs microbiens qui

stimulent la croissance drsquoautres microorganismes

La neacutecessiteacute du caractegravere vivant des souches est ajouteacute agrave la deacutefinition par Roy Fuller en 1989

Alfred Nissle-Isolement en 1917 drsquoune souche de E coli agrave partir de selles drsquoun soldat qui lors drsquoune eacutepideacutemie de Shigellose nrsquoa pas deacuteveloppeacute drsquoenteacuterocolite -Utilisation de sa souche avec succegraves dans des cas de Salmonellose et Shigellose [Nissle 1959]

Probiotiques

Essais controcircleacutes et diarrheacutee post-antibiotique

DrsquoSouza 2002 BMJ

Cremonini 2002 Aliment Pharmocol Ther

Szajewska 2005 Aliment Pharmocol Ther

Hawrelak 2005 Digestion

Szajewska 2006 J Pediatr

Johnston 2006 CMAJ

Johnston 2007 Cochrane Database Syst Rev

Adulte

Enfant

Efficaciteacute modeacutereacutee des probiotiques agrave preacutevenir la diarrheacutee post-ATB

bullS boulardii ou L rhamnosus GG chez lrsquoenfantbullL casei DN 114 001 chez la personne acircgeacuteebullPb dans la deacutefinition de la diarrheacutee et de la graviteacute clinique

Essais controcircleacutes et colite agrave Clostridium difficile

Lewis 2007 Am J Gastroenterol PourDendukuri 2005 CMAJ Contre

Difficulteacute agrave discerner preacutevention et traitement au moment de la colite

Proc Natl Acad Sci USA 2011

Ampicillin (1 gL) vancomycin (500 mgL) neomycin sulfate (1 gL) and metronidazole (1 gL) in drinking water for 4 wk before PR8 virus infection (10 pfu per mouse)

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51

Alfred Nissle-Isolement en 1917 drsquoune souche de E coli agrave partir de selles drsquoun soldat qui lors drsquoune eacutepideacutemie de Shigellose nrsquoa pas deacuteveloppeacute drsquoenteacuterocolite -Utilisation de sa souche avec succegraves dans des cas de Salmonellose et Shigellose [Nissle 1959]

Probiotiques

Essais controcircleacutes et diarrheacutee post-antibiotique

DrsquoSouza 2002 BMJ

Cremonini 2002 Aliment Pharmocol Ther

Szajewska 2005 Aliment Pharmocol Ther

Hawrelak 2005 Digestion

Szajewska 2006 J Pediatr

Johnston 2006 CMAJ

Johnston 2007 Cochrane Database Syst Rev

Adulte

Enfant

Efficaciteacute modeacutereacutee des probiotiques agrave preacutevenir la diarrheacutee post-ATB

bullS boulardii ou L rhamnosus GG chez lrsquoenfantbullL casei DN 114 001 chez la personne acircgeacuteebullPb dans la deacutefinition de la diarrheacutee et de la graviteacute clinique

Essais controcircleacutes et colite agrave Clostridium difficile

Lewis 2007 Am J Gastroenterol PourDendukuri 2005 CMAJ Contre

Difficulteacute agrave discerner preacutevention et traitement au moment de la colite

Proc Natl Acad Sci USA 2011

Ampicillin (1 gL) vancomycin (500 mgL) neomycin sulfate (1 gL) and metronidazole (1 gL) in drinking water for 4 wk before PR8 virus infection (10 pfu per mouse)

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51

Essais controcircleacutes et diarrheacutee post-antibiotique

DrsquoSouza 2002 BMJ

Cremonini 2002 Aliment Pharmocol Ther

Szajewska 2005 Aliment Pharmocol Ther

Hawrelak 2005 Digestion

Szajewska 2006 J Pediatr

Johnston 2006 CMAJ

Johnston 2007 Cochrane Database Syst Rev

Adulte

Enfant

Efficaciteacute modeacutereacutee des probiotiques agrave preacutevenir la diarrheacutee post-ATB

bullS boulardii ou L rhamnosus GG chez lrsquoenfantbullL casei DN 114 001 chez la personne acircgeacuteebullPb dans la deacutefinition de la diarrheacutee et de la graviteacute clinique

Essais controcircleacutes et colite agrave Clostridium difficile

Lewis 2007 Am J Gastroenterol PourDendukuri 2005 CMAJ Contre

Difficulteacute agrave discerner preacutevention et traitement au moment de la colite

Proc Natl Acad Sci USA 2011

Ampicillin (1 gL) vancomycin (500 mgL) neomycin sulfate (1 gL) and metronidazole (1 gL) in drinking water for 4 wk before PR8 virus infection (10 pfu per mouse)

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51

Essais controcircleacutes et colite agrave Clostridium difficile

Lewis 2007 Am J Gastroenterol PourDendukuri 2005 CMAJ Contre

Difficulteacute agrave discerner preacutevention et traitement au moment de la colite

Proc Natl Acad Sci USA 2011

Ampicillin (1 gL) vancomycin (500 mgL) neomycin sulfate (1 gL) and metronidazole (1 gL) in drinking water for 4 wk before PR8 virus infection (10 pfu per mouse)

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51

Proc Natl Acad Sci USA 2011

Ampicillin (1 gL) vancomycin (500 mgL) neomycin sulfate (1 gL) and metronidazole (1 gL) in drinking water for 4 wk before PR8 virus infection (10 pfu per mouse)

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51

Bakken et al Anaerobe 2009

Greffe de florehellip

• Slide 1
• Slide 2
• Slide 3
• Slide 4
• Slide 5
• Slide 6
• Slide 7
• Slide 8
• Slide 9
• Slide 10
• Slide 11
• Slide 12
• Slide 13
• Slide 14
• Slide 15
• Slide 16
• Slide 17
• Slide 18
• Slide 19
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Slide 33
• Slide 34
• Slide 35
• Slide 36
• Slide 37
• Slide 38
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Slide 43
• Slide 44
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51