Effect of clarithromycin in patients with sepsis and ventilatorassociated pneumonia Ppt Powerpoint Presentation slides Evangelos Giamarellos-Bourboulis Medical Slideshow Pneumococcal Pneumonia in Patients Requiring Hospitalization: Effects ...

Effect of clarithromycin in patients with sepsis and ventilatorassociated pneumonia

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Slide 1 :

IMMUNOMODULATORY THERAPIES FOR SEPSIS: UNEXPECTED EFFECTS OF MACROLIDES E. J. Giamarellos-Bourboulis, MD Assistant Professor of Medicine 4th Department of Internal Medicine University of Athens, Medical School, Greece

Slide 2 :

A DIFFERENT EXPERIMENTAL APPROACH: SIMULATION OF CLINICAL PRACTICE IV Clarithromycin ? survival ? TNFa release by monocytes ? tissue bacterial growth ? tissue inflammation Challenge by: a) Susceptible E.coli b) MDR P.aeruginosa c) MDR K. pneumoniae EXPERIMENTAL SEPSIS Giamarellos-Bourboulis EJ, et al. AAC 2004, 48: 93 Giamarellos-Bourboulis EJ, et al. IJAA 2005, 25: 168 Giamarellos-Bourboulis EJ, et al. Scand J Infect Dis 2005, 37: 48 Giamarellos-Bourboulis EJ, et al. BMC Infect Dis 2006, 6: 31 Giamarellos-Bourboulis EJ, et al. JAC 2006, 57: 937

Slide 3 :

A DIFFERENT CLINICAL APPROACH PATIENTS UNDER SURVEILLANCE i.e. ICU Inclusion Criteria Start of Therapy ALL WITH THE SAME INFECTION RECORDED DATA: ANTIMICROBIALS

Slide 4 :

www.clinicaltrials.gov (NCT 00297674) Clin Infect Dis 2008; 46: 1157-1164

Slide 5 :

STUDY DESIGN 200 patients with VAP and sepsis Three centers ?18 years + VAP + Sepsis/Severe Sepsis/Septic Shock (ACCP/SCCM 1992)

Slide 6 :

EXCLUSION CRITERIA HIV infection Corticosteroids > 1 month Neutropenia (<500/mm3) Administration of aPC preceding five days AV block of 2nd or 3rd degree

Slide 7 :

DEFINITION OF VAP Purulent tracheobronchial secretions New or persistent consolidation in lung X-ray Clinical Pulmonary Infection Score >6 Baughman RP. Curr Opin Crit Care 2003, 9: 397 Camargo LFA, et al. Crit Care 2004, 8: R422 Chastre & Fagon. Am J Resp Crit Care Med 2002, 165: 867 Mayhall CG. Emerg Infect Dis 2001, 7: 200 Michel F, et al. Chest 2005, 127: 589

Slide 8 :

GROUPS OF TREATMENT 200 patients 100 PLACEBO + ANTIBIOTICS 100 CLARITHROMYCIN + ANTIBIOTICS 1000mg iv daily within one hour x 3 days

Slide 9 :

FOLLOW-UP OF PATIENTS (DAYS) Signs of organ failure Quantitative TBS cultures Resolution of VAP Weaning from MV 1 7 15 22 28

Slide 10 :

BASELINE DEMOGRAPHIC CHARACTERISTICS (1) *non-significant **Clinical Pulmonary Infection Score

Slide 11 :

BASELINE DEMOGRAPHIC CHARACTERISTICS (2)

Slide 12 :

ADMINISTERED ANTIMICROBIALS *non-significant

Slide 13 :

ADEQUACY OF CO-ADMINISTERED ANTIMICROBIALS Day 0 Day 5 Day 10 100 80 60 40 20 0 Susceptibility to administered regimen Eradication of pathogen pNS pNS pNS PLACEBO CLARITHROMYCIN

Slide 14 :

SERIOUS ADVERSE EVENTS Bronchospasm (1): resolved within 1 hour ? transaminases (2): resolved within 2 and 3 days respectively Subjects were not withdrawn from the study Placebo: 0 (0%) Clarithromycin: 3 (3%) pNS (p: 0.246)

Slide 15 :

DEATH BY SEPTIC SHOCK + MODS Moirtality (%) PLACEBO CLARITHROMYCIN 100 80 60 40 20 0 p: 0.020 Odds ratio for death 25 20 15 10 5 0 p: 0.043 19.00 3.78 60% 38.9%

Slide 16 :

EFFECT ON RESOLUTION OF VAP 50%: 15.5 days 50%: 10 days p: 0.011 Days % resolved cases

Slide 17 :

CHANGES OF CPIS OVER TREATMENT Day 0 Day 5 Day 10 8 6 4 2 0 Mean CPIS pNS p: 0.016 p: 0.032 PLACEBO CLARITHROMYCIN

Slide 18 :

EFFECT ON TIME TO WEANING FROM MV Days % of de-intubated patients p: 0.049 50%: 22.5 days 50%: 16 days

Slide 19 :

Mean time of transition into MODS 6 5 4 3 2 1 0 p: 0.047 PLACEBO CLARITHROMYCIN INDICATION FOR A MECHANISM?

Slide 20 :

RESULTS Administration of IV Clarithromycin Is NOT accompanied by Serious Adverse Events Prolongs considerably survival of patients with MODS + Septic Shock by decreasing 5-fold risk of death Reduces the time to resolution of VAP Reduces the time to de-intubation

Slide 21 :

ALVEOLI CLARITHROMYCIN (-) BACTERIAL BIOFLM (-) CYTOKINE PRODUCTION AIRWAYS MACROPHAGE MACROPHAGE BLOOD MONOCYTE CLINICAL EFFICACY Earlier resolution of VAP Earlier weaning from MV ? risk of death in septic shock and MODS : BACTERIUM

Slide 22 :

IV CLARITHROMYCIN FOR THE CRITICALLY ILL PATIENT Novel recommendations: Ventilator Associated Pneumonia Septic Shock =2 organ failures

	giamarel@ath.forthnet.gr 1 Years ago. Category: Internal Medicine

Tags:	Internal Medicine

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