Intracheal antibiotics administration

Transcription

1 Intracheal antibiotics administration Jean Chastre, M.D.

2 Disclosure Conflicts of interest: Consulting or Lecture fees: Bayer, Pfizer, Cubist/Merck, Basilea, Kenta/Aridis, Roche, AstraZeneca/Medimmune

3 Frequency, % MIC Distribution of Doripenem, Meropenem and Imipenem in 875 P. aeruginosa Isolates from the United States Doripenem Meropenem Imipenem Pillar CM, et al. Antimicrob Agents Chemother. 2008;52: DRP breakpoint MER breakpoint IMP breakpoint 0 0,03 0,06 0,12 0,25 0, >32 MIC 90 (ug/ml)

4 Penetration of Meropenem into Epithelial Lining Fluid of 39 Patients with VAP Lodise TP, et al. AAC 2011;55: Median AUC ELF /AUC plasma penetration ratio =25.4% Plasma concentration ELF concentration

5 o o o o o Factors influencing nebulization efficiency Size of the particles Aerosol generator Ventilator circuit Ventilator settings Type and severity of lung lesions

6 Particles deposition in the airways is directly related to their size OPC Bronchi Deep lung compartment Size >5 µm Size 2-5 µm Size 1-3 µm Size <1 µm: droplets exhaled with expiratory gases

7 Jet nebulizers Aerosol generated by gas either continuously (wall system), or during inspiration (gas flow from the ventilator). Although particles size are usually small, it can vary from one brand to another. May interfere with tidal volume delivering.

8 Ultrasonic nebulizers May degrade heat-sensitive drugs

9 Vibrating-mesh nebulizers Potentials advantages: Aerosol generated by the vibration of an aperture plate Droplet size is small and very well calibrated Antibiotic solution is not heated the aerosol generation can be synchronized with inspiration minimizing aerosol waste during exhalation. Connector Aperture Plate Oscillator Washer Vibrational Element

10 Four key practices for optimal antibiotic nebulization during mechanical ventilation Ari A, et al. Respir Care Jul;55(7): st Remove the heat and moisture exchanger during nebulization

11 Four key practices for optimal antibiotic nebulization during mechanical ventilation 2 nd Ari A, et al. Respir Care Jul;55(7):837-44

12 3 rd Four key practices for optimal antibiotic nebulization during mechanical ventilation Ehrmann S., et al. Ann Intensive Care Dec;7(1):78

13 Four key practices for optimal antibiotic nebulization during mechanical ventilation Ehrmann S., et al. Ann Intensive Care Dec;7(1):78 4 th

14 Nebulizing antibiotics in the ICU: Doing a better job Ehrmann S., et al. Ann Intensive Care Dec;7(1):78 1. Use a checklist. Ensure adequate staff training. 2. Use an ultrasonic or mesh-vibrating nebulizer. 3. Use specific formulations for inhalation. 4. Position the nebulizer (continuous delivery) upstream in the inspiratory limb at cm of the Y-piece. 5. Remove the HME during nebulization; if using a heated humidifier, switch it off. 6. Use volume-controlled, low RR, low inspiratory flow MV. 7. Place a new filter between the expiratory limb and the ventilator. 8. Monitor patients closely during the nebulization, particularly in regard to airway pressure, arterial pressure and SaO2. 9. Resume humidification at the end of the nebulization.

15 Intratracheal Administration of Antimicrobial Agents in Ventilated Adults: An International Survey on Delivery Practices and Safety Solé-Lleonart C., et al. Respir Care Aug;61(8):1008-1

16 Proprietary Vibrating Mesh Delivery System (Necktar-Aerogen )

17 Amikacin Inhale on-vent configuration is integrated directly at the endotracheal tube Compatible with standard settings Enables synchronisation Positioned near ET tube No need to switch off Nebulisation takes ~36 minutes depending on ventilator settings 2 ET, endotracheal. 1. Bayer. Amikacin Inhale Instructions For Use 2016 v14_5-2; 2. Luyt CE et al. Crit Care 2009;13:R

18 BAY achieves bactericidal tracheal aspirate amikacin concentrations in ventilated patients with GNB pneumonia Niederman MS, et al. Intensive Care Med. 2012;38(2):263-71

19 ELF Amikacin Concentrations in 28 Patients with GNB VAP Having Received Nebulized amikacin (400 mg bid) for 7 14 days Luyt CE, et al. Crit Care 2009 ELF amikacin concentration (µg/ml) 16,000 10,000 3,000 2,500 2,000 1,500 1,

20 Serum Amikacin Concentrations in 28 Patients with GNB VAP Having Received Nebulized amikacin (400 mg bid) for 7 14 days Serum amikacin concentration (µg/ml) 6 Luyt CE, et al. Crit Care No. of patients D1 28 D2 28 D3 28 D4 25 D5 21 D6 22 D7 20 D8 2 D9 2 D10 1

21 Inhaled Antibiotics for HAP/VAP: The PRO o Strong rationale o Improvement in device technology and processes permits to achieve high antibiotic pulmonary deposition o Results of experimental animal models are encouraging, as well as preliminary data obtained in ICU patients

22 Nebulized versus intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa Lu Q. et al. Intensive Care Med 2010;36:

23 Clinical cure Nebulized antibiotics for VAP: a systematic review and meta-analysis Zampieri FG, et al. Critical Care 2015;19:150

24 Mortality Nebulized antibiotics for VAP: a systematic review and meta-analysis Zampieri FG, et al. Critical Care 2015;19:150

25 A randomized trial of the amikacin fosfomycin inhalation system for the adjunctive therapy of GNB VAP: The IASIS Trial Kollef MH, et al. Chest. 2017;151: ) 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group CPIS score Survival

26 INHALE trial design

27

28 Management of Adults With HAP and VAP: 2016 Clinical Practice Guidelines by the IDSA and the ATS Kalil AC, et al. Clin Infect Dis Sep 1;63(5):e61-e111 Recommendation For patients with VAP due to GNB that are susceptible to only aminoglycosides or polymyxins, we suggest both inhaled and systemic antibiotics, rather than systemic antibiotics alone (weak recommendation, very low-quality evidence).

29 Aerosolized antibiotics Placebo Palmer LB and Smaldone GC AJRCCM 2014 o Double-blind placebo-controlled study conducted in 42 ICU patients with VAT/VAP o AA selection (vancomycin and/or AG) was determined on the basis of sputum Gram stain o Medication or placebo was nebulized via an AeroTech II nebulizer o Growth was quantified using a graded scale of 0-4 from semi-quantitative cultures MDR GNB Nonresistant GNB Resistant Gram positives Nonresistant Gram positives X Newly resistant organisms

30 Reduction of Bacterial Resistance with Inhaled Antibiotics in the ICU Palmer LB and Smaldone GC. Am J Respir Crit Care Med 2014;189: