Your SlideShare is downloading. ×
0
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Nebulized antibiotics for treating Ventilator-Associated Pneumonia
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Nebulized antibiotics for treating Ventilator-Associated Pneumonia

1,213

Published on

VHIR Seminar led by prof. Jean-Jacques Rouby, from the Réanimation Polyvalente Département d'Anesthésie-Réanimation Faculté de Médecine Pierre et Marie Curie UPMC Hôpital Pitié-Salpêtrière Assistance …

VHIR Seminar led by prof. Jean-Jacques Rouby, from the Réanimation Polyvalente Département d'Anesthésie-Réanimation Faculté de Médecine Pierre et Marie Curie UPMC Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris.

Abstract:
1 - What we have learnt from experimental studies: relevant animal models,
optimization of aerosol delivery during mechanical ventilation,
penetration of aerosolized antibiotics within the infected parenchyma,
toxicity and pharmacokinetics
2 - the existing human litterature concerning nebulization of antibiotics
in critically ill patients with Ventilator-Associated Pneumonia
3 - The promising place of nebulized colistin and vancomycin for treating
multi-drug resistant Ventilator-Associated Pneumonia

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
1,213
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
57
Comments
0
Likes
2
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Nebulized antibiotics for ventilator-associated pneumonia Multidisiplinary Intensive Care Unit Department of Anesthesiology and Critical Care, Pitié Salpêtrière hospital, University Pierre and Marie Curie (UPMC) Paris 6 Jean-Jacques Rouby Paris http://www.reapitie-univparis6.aphp.fr
  • 2. Potential benefits of using the inhaled rather than the intravenous route 2 – Increase the bactericidal efficiency by increasing lung tissue concentrations. 1 – Reach directly the infected lung parenchyma without crossing cell membranes Ventilator Nebulizer 3 - Decrease systemic toxicity.
  • 3. Conditions required to reach the deep lungConditions required to reach the deep lung Optimisation of aerosol particles size Extrapulmonary deposition Specific issues related to antibiotic nebulization Type of nebulizer
  • 4. Ultrasonic and vibrating plate nebulizers are more performant than jet nebulizersUltrasonic and vibrating plate nebulizers are more performant than jet nebulizers (Ferrari et al ICM 34: 1718-1723, 2008(Ferrari et al ICM 34: 1718-1723, 2008 )) Ventilator settings should beVentilator settings should be modified during the nebulizationmodified during the nebulization period to limit inspiratory flowperiod to limit inspiratory flow turbulencesturbulences ++++++ Patients should be synchronized with the ventilator to avoid turbulences which increase extrapulmonary deposition (propofol) 50 % of the particles should have a diameter < 5 µ
  • 5. If nebulization is optimized, 40-70% of the dose deposited in the nebulizer chamber reaches the deep lung Initial dose inserted into the nebulizer’s chamber Nebulized dose Chamber depositChamber deposit Upper airways depositUpper airways deposit Pulmonary dose alveoliBronchioles Exhaled doseExhaled dose Expiration and tracheal suctioning Circuits depositCircuits deposit Inhaled dose Systemic absorption Urinary excretion J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012
  • 6. O’Doherty et al, Am Rev Respi Dis, 1992 (146) 383-8 Low respiratory frequency (12 bpm) Plateau inspiratory pause (20%) Specific ventilator settings for decreasing inspiratory flow turbulences High I/E ratio (50%) Propofol sedation is often necessary to synchronize the patient with the ventilator
  • 7. Expiratory filter Ventilator Nebulizer Rationale for determining the nebulized dose Dose delivered to the tracheobronchial tree = intravenous dose Dose in the nebulizer = dose delivered to the tracheobronchial tree + extra-pulmonary deposition J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012
  • 8. Before clinical use, experimental studies reproducing conditions observed in ventilated critically ill patients J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012 Experimental models should concern big animals whose cradiopulmonary physiology is close to humans and a critical care environment allowing prolonged mechanical ventilation
  • 9. Experimental Intensive Care UnitExperimental Intensive Care Unit Département Hospitalo-Universitaire de Recherche ExpérimentaleDépartement Hospitalo-Universitaire de Recherche Expérimentale de Lille (Pr Charles-Hugo Marquette)de Lille (Pr Charles-Hugo Marquette) Big animals: piglets and pigsBig animals: piglets and pigs Prolonged mechanical ventilationProlonged mechanical ventilation Post-mortem pulmonary samplesPost-mortem pulmonary samples J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012
  • 10. J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012 In 1997 an Experimental Intensive Care UnitExperimental Intensive Care Unit allowing the prolonged mechanical ventilation of piglets with inoculation bacterial pneumonia was set up Anesthetized intubated piglets weighing 20 kg, mechanically ventilated Bronchoscopic inoculation in middle and lower lobes of 40- 60 ml of a solution containing 10 5 - 10 6 Escherichia coli or Pseudomonas aeruginosa The animals are mechanically ventilated for 1 to 4 days
  • 11. J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012 Multiple hilar and juxtapleural lung tissue samples for histologic and bacteriologic examination and measurement of antibiotic tissue concentrations At the end of the experiments, animals are sacrified for multiple lung tisssue sampling At the end of the experiments, animals are sacrified for multiple lung tisssue sampling Death Sternotomy Exsanguination
  • 12. Did experimental studies confirm the potential benefits of nebulized antibiotics ? 1 – YES, high tissue concentrations in the infected lung parenchyma were demonstrated Extrapulmonary deposition can be limited to 30-40% if nebulization is optimized 10% to 20 % of the dose inserted into the nebulizer chamber reaches the infected lung parenchyma
  • 13. 2 – YES, potent and rapid bactericidal effect was demonstrated in animals with inoculation pneumonia. Ferrari et al, Intensive Care Medicine 2009 35: 1792-1800 Time-dépendant antibiotics Ceftazidime Tonnellier et al, Anesthesiology 102: 995-1000, 2005 Concentration-dependant antibiotics Amikacin Colistin Goldstein I et al , AJRCCM 165 :172-175, 2002 Goldstein I et al , AJRCCM, 166, 1375 - 1381, 2002 Lu et al, Intensive Care Medicine 36: 1147-1155, 2010 Elman et al, Anesthesiology 97: 199-206, 2002 Did experimental studies confirm the potential benefits of nebulized antibiotics ?
  • 14. Goldstein I et al , AJRCCM, 166, 1375 - 1381, 2002 Piglets with inoculation Escherichia coli pneumonia : comparison between nebulized and IV amikacin ( 45 vs 15 mg.kg -1 ) Piglets with inoculation Escherichia coli pneumonia : comparison between nebulized and IV amikacin ( 45 vs 15 mg.kg -1 ) MIC50 Bactericidal effect ++++ following 24h treatment and 2 nebulizations amikacin, concentration- dependant antibiotic
  • 15. Ferrari et al, Intensive Care Medicine 2009 35: 1792-1800 Piglets with inoculation pneumonia caused by Pseudomonas aeruginosa partially resistive to ceftazidime: comparison between nebulized (/3 h) and continuous IV ceftazidime ( 200 vs 100 mg.kg -1 ) Piglets with inoculation pneumonia caused by Pseudomonas aeruginosa partially resistive to ceftazidime: comparison between nebulized (/3 h) and continuous IV ceftazidime ( 200 vs 100 mg.kg -1 ) ceftazidime, time-dependant antibiotic MIC50 Aerosol IV Bactericidal effect ++++ following 24h treatment and 9 nebulizations
  • 16. Aerosol IV Piglets with inoculation pneumonia caused by Pseudomonas aeruginosa partially resistive to ceftazidime: : comparison between nebulized and IV colistin ( 56 000 IU vs 40000 IU.kg -1 ) Piglets with inoculation pneumonia caused by Pseudomonas aeruginosa partially resistive to ceftazidime: : comparison between nebulized and IV colistin ( 56 000 IU vs 40000 IU.kg -1 ) colistin, concentration- dependant antibiotic Bactericidal effect ++++ following 24h treatment and 3 nebulizations Lu et al, Intensive Care Medicine 36: 1147-1155 2010
  • 17. Antibiotic tissue concentrations decrease with lung aeration and histological severity of pneumonia Elman M et al , Anesthesiology, 97, 199-206, 2002 Nebulized amikacin Lu et al, Intensive Care Medicine 36: 1147-1155 2010 Nebulized colistin Histological grade of pneumonia
  • 18. 3 - NO, as far as systemic toxicity is concerned. Lung infection impairs the « barrier effect » of alveolar-capillary  membrane and allows systemic diffusion of most nebulized  antibiotics (amikacin and ceftazidime)  A single exception: colistin has a very low systemic diffusion in presence of lung infection J.J. Rouby, Bouhemad B., Monsel A., Brisson H., Arbelot C., Lu Q. and the Nebulized Antibiotics Study Group. Aerosolized antibiotics for Ventilator-Associated pneumonia: Lessons from experimental studies. ANESTHESIOLOGY 117:1364-1380, 2012 Did experimental studies confirm the potential benefits of nebulized antibiotics ?
  • 19. Plasma pharmacokinetics following nebulization of amikacin : healthy lungshealthy lungs vs infected lungs 30 Time after nebulization (h) 0 5 10 15 20 25 amikacinplasmaµg/ml 0 5 10 15 20 25 30 35 Healthy lungs Infected lungs Goldstein I et al , AJRCCM 165 :172-175, 2002 Goldstein I et al , AJRCCM, 166, 1375 - 1381, 2002 5858 ±± 18 %18 % of the administered dose isof the administered dose is eliminated in the urineseliminated in the urines 7474 ± 12 %± 12 % of the administered dose isof the administered dose is eliminated in the urineseliminated in the urines
  • 20. Plasma and tissue pharmacokinetics following administration of 1 to 4 aerosols of amikacin 45 mg/kg Ferrari F et al , Anesthesiology, 98, 1016 - 1019, 2003 Plasma elimination Urinary elimination Tissue concentrations Tissue concentrations
  • 21. Plasma pharmacokinetics following nebulized and intravenous amikacin (45 vs 15 mg/kg) Goldstein I et al , AJRCCM, 166, 1375 - 1381, 2002 Aerosol IV
  • 22. Ferrari et al, Intensive Care Medicine 2009 35: 1792-1800 Plasma pharmacokinetics following nebulized and intravenous ceftazidim ( 200 vs 100 mg.kg -1 )
  • 23. Lu et al, Intensive Care Medicine 2010 36: 1147-1155 Plasma pharmacokinetics following nebulized and intravenous colistin (56 000 IU vs 40000 IU.kg -1 )
  • 24. Experimental studies in pigs and piglets are encouraging: high tissue concentrations in the infected parenchyma and rapid and efficient bactericidal activity Experimental studies: summary Nebulization should be optimized: doses adapted to extrapulmonary deposition and specific ventilator settings +++ Intravenous colistin does not diffuse in infected lung parenchyma. Nebulized colistin has a very low systemic diffusion that could decrease its renal toxicity. Aminoglycosides and cephalosporins systemic toxicity is not reduced by nebulization.
  • 25. A double blind study against placebo combining intravenous and nebulized antibiotics Clinical studies Palmmer et al, Critical Care Medicine 2008 36: 2008-2012
  • 26. 1. VA-Tracheobronchitis 2. Vanco or genta acoording to BGN or Cocci + 2. IV Ab in both groups (IV: 89%, Aerosol: 63%) Crit Care Med 2008, 36: 2008-12
  • 27. 1. VA-Tracheobronchitis 2. Vanco or genta acoording to BGN or Cocci + 2. IV Ab in both groups (IV: 89%, Aerosol: 63%) Crit Care Med 2008, 36: 2008-12 Resistive micoorganisms at the end of treatment:
  • 28. A double blind study against placebo combining intravenous and nebulized antibiotics Clinical studies A randomized phase II trial compa- ring nebulized and IV antibiotics in Pseudomonas aeruginosa VAP
  • 29. AJRCCM 2011, 184: 106-115 Respirateur Nébuliseur Dose delivered to the tracheobronchial tree = intravenous dose Dose in the nebulizer = dose delivered to the tracheobronchial tree + extra-pulmonary deposition
  • 30. Aerosol (n=25) Randomization Intravenous (n=25) ceftazidime 15 mg/kg/3h ceftazidime (continuous) or imipenem (I species) amikacin 25 mg/kg/24h amikacin ou cipro/ fosfo (I species) D 9 D 1 D 4 D 3 D 2 D 6 D 8 Patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa Exclusion criteria - positive blood cultures - extrapulmonary infection - Pseudomonas aeruginosa resistive to ceftazidime and/or amikacin Aims Resolution of lung infection: - clinical and biological signs - CT lung re-aeration - CT decrease in lung tissue Duration of MV D 14 BAL 5 TDM Day 0 Pharmaco AMK BAL 1 Pharmaco AMK Pharmaco Cefta MiniBAL 2 BAL 3 TDM Day 7 Pharmaco Cefta BAL 4 Randomized monocenterstudy Phase II
  • 31. 46 patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa were included (11 were secondary included) Following randomisation, 20 patients were treated by intravenous amikacin + ceftazidime IV amikacin 30-min continuous administration Daily dose 15 mg.kg-1 + IV ceftazidime 24-hr continuous administration Daily dose 90 mg.kg-1 Bolus dose = 30 mg.kg-1
  • 32. Following randomisation, 20 patients were treated by nebulized amikacin + ceftazidime + Nebulized amikacin 30-min nebulization / 24 hr Daily dose 25 mg.kg-1 -optimization of ventilatory settings (sedation by propofol during the nebulization) Nebulized ceftazidime Daily dose 120 mg.kg-1 30-min nebulization / 3 hr -optimization of ventilatory settings (sedation by propofol during the nebulization) vibrating plate nebulizervibrating plate nebulizer
  • 33. Comparative efficiency of intravenous and inhaled antibiotics Aerosol n=20 Intravenous n=20 p Value Cure of P aeruginosa VAP at day 9 (n, %) 14 (70) 11 (55) 0.33 Persisting P aeruginosa VAP at day 9 (n, %) 3 (15%) 6 (30%) 0.26 VAP caused by superinfection at day 9 (n, %) 3 (15%) 3 (15%) NS In the 6 patients of the IV group with persisting VAP, 3 were infected by P aeruginosa intermediate to amikacin and/or ceftazidime
  • 34. Temperature Blood leucocytes Tracheal secretions Oxygenation: PaO2/FiO2 Progression of pulmonary infiltrates Culture of mini-BAL Evolution of Clinical Pulmonary Infection Score (CPIS) p < 0.01 p < 0.01 CPIS Period of Treatment D0 D3 D5 D7 D9 0 2 4 6 8 10 IV (n =18) Aero (n =17)
  • 35. Computed Tomography aeration and tissue changes in infected lung regions Volume of gas in infected lung regions (ml) D 0 D 8 -100 0 100 200 300 400 500 600 700 Aero (n =17) IV (n =16) } nsp < 0.01 D 0 D 8 100 200 300 400 500 600 700 800 900 Aero (n =17) IV (n 16) }ns p < 0.01 Volume of tissue in infected lung regions (ml)
  • 36. Before neb (D0 ) Pulmonary re-aeration ( ) and decrease in lung tissue ( ) following nebulization of ceftazidime (8 days) and amikacin (3 days) in a patient with VAP caused by sensitive Pseudomonas aeruginosa 53-year old patient with VAP53-year old patient with VAP following aortic surgeryfollowing aortic surgery After neb (D8 ) Changes of Gas and Tissue Volumes (ml) -200 0 200 400 600 800 1000 Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa Qin Lu et al. Am J Resp Crit Care Med 2011
  • 37. Changes of Gas and Tissue Volumes (ml) -200 0 200 400 600 800 1000 Before neb (D0 ) Pulmonary re-aeration ( ) and decrease in lung tissue ( ) following nebulization of ceftazidime (6 days) and amikacin (3 days) in a patient with VAP caused by partially resistant Pseudomonas aeruginosa (MIC 16 µ/ml) 32-year old patient suffering32-year old patient suffering from multiple traumafrom multiple trauma After neb (D8 ) Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa Qin Lu et al. Am J Resp Crit Care Med 2011
  • 38. No difference concernant in amikacin toxicity Amikacin trough concentrations (mg/L) IV Aerosol 0 2 4 6 8 10 D 1 NS IV Aerosol 0 2 4 6 8 10 D 3 NS Amikacin trough concentrations (mg/L)
  • 39. Bacteriological results Patients n = 20 (Intravenous antibiotics) D0 D3 D5 D7 D9 D14 Number of mini-BAL 20 16 15 10 11 4 Nb of BAL Pseudomonas aeruginosa + 20 8 8 5 6 1 Pseudomonas resistant to Ceftazidime and/or amikacin 0 0 33 44 3 0 Relapse due to P aeruginosa Cefta/Amk R - - - 4 0 Patients n = 20 (Nebulized antibiotics) D0 D3 D5 D7 D9 D14 Number of mini-BAL 20 17 16 12 12 11 Nb of BAL Pseudomonas aeruginosa + 17 1 0 2 5 4 Pseudomonas resistant to Ceftazidime 0 0 00 00 0 1 Relapse due to Ps aeruginosa Cefta S - - - 2 3 Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa Qin Lu et al. Am J Resp Crit Care Med 2011
  • 40. Conclusions of the Phase II trial Antibiotic nebulization More efficient and rapid eradication of Pseudomonas aeruginosa from distal pulmonary samples Prevention of per-treatment acquisition of antibiotic resistance Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa Qin Lu et al. Am J Resp Crit Care Med 2011 Efficient treatment of VAP caused by Pseudomonas aeruginosa with decreased sensitivity to ceftazidime and/or amikacin
  • 41. A double blind study against placebo combining IV and nebulized antibiotics Clinical studies A randomized phase II trial comparing nebulized and IV antibiotics in Pseudomonas aeruginosa VAP Many observationnal studies reporting the efficiency of nebulized antibiotics for treating VAP caused by multidrug resistive Pseudomonas aeruginosa or Acinetobacter baumanïi.
  • 42. http://www.reapitie-univparis6.aphp.fr/ ANESTHESIOLOGY. 117:1335-1347, 2012
  • 43. Rationale for using high doses colistin http://www.reapitie-univparis6.aphp.fr/ Colistin 100 00 UI/kg
  • 44. http://www.reapitie-univparis6.aphp.fr/ Monocenter prospective, non-randomized observational study performed during 4 years in the 26-bed multidiciplinary ICU of La Pitié-Salpêtrière hospital Noninferiority study on cure rate of VAP caused by multidrug resistive microorganims. Noninferiority of nebulized colistin was demonstrated if the lower limit of the one-sided 95% CI for difference in clinical cure rate was more than −16%. ANESTHESIOLOGY. 117:1335-1347, 2012
  • 45. http://www.reapitie-univparis6.aphp.fr/ Inclusion and exclusion flow chart Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012
  • 46. Colistin 220 00 UI/kg http://www.reapitie-univparis6.aphp.fr/ Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012 Patients included in the study IV β
  • 47. Patients with multidrug resistive VAP are more severe http://www.reapitie-univparis6.aphp.fr/
  • 48. Similar cure rate at day 14: 67 % for Pseudomonas aeruginosa 100 % for Acinetobacter baumaniï http://www.reapitie-univparis6.aphp.fr/
  • 49. http://www.reapitie-univparis6.aphp.fr/ Frequent recurrence for VAP caused by Pseudomonas aeruginosa 26 % not observed for Acinetobacter baumaniï 0 % Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012
  • 50. http://www.reapitie-univparis6.aphp.fr/ Success Failure Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012
  • 51. Colistin renal toxicity http://www.reapitie-univparis6.aphp.fr/ Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012
  • 52. Conclusions 2 – Cure rate of VAP caused by multidrug resistive Pseudomonas aeruginosa reaches 67 %, a result similar to that obtained in VAP caused by sensitive strains. 4 – Recurrence rate reaches 30 % for Pseudomonas aeruginosa and is unfrequently observed withAcinetobacter baumanï 1 – High doses colistin can be nebulized with good clinical acceptance and without renal toxicity http://www.reapitie-univparis6.aphp.fr/ 3 – Cure rate of VAP caused by multidrug resistive Acinetobacter baumanï reaches 100%, a result similar to that obtained in VAP caused by sensitive strains. Q. Lu, Luo R., Bodin L., Yang J., Zahr N., Aubry A., Golmard J.L., Rouby J.J.; the Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in Ventialator-associated pneumonia caused by Multidrug-resistant Pseudomonas aeruginosa et Acinetobacter Baumanïi ANESTHESIOLOGY. 117:1335-1347, 2012
  • 53. General conclusions 1) Inhaled antibiotics provide mare rapid bacterial killing and similar clinical efficiency for treating ventilator-associated pneumonia. 2) Intravenous antibiotics often induce rapid resistance to various microorganisms, particularly Pseudomona aeruginosa 3) Inhaled antibiotics prevent per-treatment acquisition of resistance 5) Ventilator-associated pneumonia caused by resistive Pseudomonas aeruginosa or Acinetobacter baumanii can be efficiently treated by nebulized colistin

×