Ventilator Associated Pneumonia ICU Fellowship Training Radboudumc
Attributable mortality VAP Meta-analysis of individual patient data from randomized prevention studies Attributable mortality mainly results from longer stay in the ICU Melsen WG. Lancet 2013
The problem Clinical criteria Antibiotics No antibiotics Sensitivity 69% Specificity 75% Selection multiresistant micro-organisms Inadequate treatment increases mortality The importance of quantitative cultures is not consistent
Incidence of VAP? Prospective cohort & nonrandomized trials (N = 38) Control arms in randomized trials (N = 51) Safdar N. Crit Care Med 2005;33:2184-2193
ICU acquired infection Potential Pathogenic M.O. Reservoir Other patient Digestive tract Surroundings Colonisation Infection
Pathophysiology VAP N = 64 Tracheal aspirate 17 PPMO (85%) Gastric aspirate 6 PPMO (20%) Pneumonia N = 14 20 PPMO Bonten MJ. Chest 1994;105:878-884
Exogenous source Oral colonisation Endogenous source Accumulation of secretions above cuff Colonization of Trachea Pneumonia
Bed head elevation Niel-Weise BS. Crit Care 2011;15:R111
A group of 22 experts recommended elevating the head of the bed of mechanically ventilated patients to a 20 to 45 degrees position and preferably in a 30 degrees position as long as it does not pose risks or conflicts with other nursing tasks, medical interventions or patients wishes. Niel-Weise BS. Crit Care 2011;15:R111
ET modifications Silver sulfadiazine
Subglottic drainage N Control Study P-value Comment Mahul 1992 145 General ICU 29,1 13 < 0,05 No BAL or PSB Valles 1995 153 General ICU 39.6/1000 19.9/1000 0,03 BAL/PSB Kollef 1999 343 Cardiac ICU 8,2% 5% 0,238 No BAL or PSB Smulders 2002 150 General ICU 16% 4% 0,014 No BAL or PSB Lorente 2007 280 General ICU 22,1% 7,9% 0,001 No BAL or PSB We recently finished a RCT on subglottic drainage after tracheostomy
Subglottic drainage 40 Subglottic drainage (n=169) p=0.02 Control (n=164) p=0.01 Incidence, % 30 20 10 15 26 p=0.02 18 33 0 1 VAP total VAP early VAP late 6 ARR 11% < 5 days 5 days Lacherade JC. Am J Respir Crit Care Med 2010; 182:910-917
Lacherade JC. Am J Respir Crit Care Med 2010; 182:910-917 Secondary outcomes 16 13 14,8 10 6 10,1 11,6 8,0 7,0 11,0 11,0 3 4,5 0 PED, % Tracheostomy, % MV, d LOS, d No difference in mortality
Subglottic drainage Reduces LOS and duration of MV but not mortality Muscedere J. Crit Care Med 2011
SDD and SOD NS 30 NS 27,5 26,6 26,9 Crude mortality (%) 20 10 After correction for baseline differences absolute mortality reduction with SDD and SOD of 3.5 and 2.9% respectively 0 Control (N = 1990) SOD (N = 1904) SDD (N = 2045) de Smet AMGA. N Engl J Med 2009;360:20-31
Colonisation with resistant Gr- organisms 20 Ceftazidime - rectal isolates % colonised 10 0 0 12 24 Time (months) Oostdijk EAN. Am J Respir Crit Care Med 2010;181:452-457
Colonisation with BMRO de Smet AMGA. Lancet Inf Dis 2011
Oral decontamination and antibiotic resistance SDD SOD 30 P < 0.001 P < 0.42 P < 0.002 22,5 24,1 25,4 15 7,5 0 11,8 5,6 5,9 4,6 Aminogl resistant Gr - D 28 mortality Bacteremia N = 11997 In both groups gradual resistance increase Oostdijk EAN. JAMA 2014
SDD Meta-analysis SOD Chlorhexidine 4266 0.85 (0.75-0.97) 0.01 0.1 1 10 100 Favours SOD Favours Control 7839 0.73 (0.64-0.84) 2618 1.25 (1.05-1.50) 0.01 0.1 1 10 100 0.01 0.1 1 10 100 Favours SDD Favours Control Favours SDD Favours Control Price R. BMJ 2014;348:g2197
Morrow LE. Am J Respir Crit Care Med 2010;182:1058-1064 Probiotics and VAP prevention RCT - N = 138 - oral/gastric Lactobaccilus rhamnosus 40 Probiotics Control P = 0.007 P = 0.02 20 30 15 20 10 10 5 0 VAP 0 Closttridium Difficile
Early vs late tracheotomy for VAP prevention N = 419 Early = 6-8 D Late = 13-15 D Early Late 25 15 20 15 10 5 14 21 10 5 P = 0.02 0 VAP % 0 MV free days D 28 No difference in mortality JAMA 2010;303:1483-1489
69% 57%
Diagnostic strategy in oncology patients with ARF Azoulay E. Am J Respir Crit Care Med 2010;182:1038-1046
Conclusion In oncology patients with ARF early FO- BAL does not increase the need for MV Approximately 15-20% of diagnoses stems from FO-BAL Non-invasive strategy is very successful and likely so in the near future Up-to-date early FO-BAL still indicated but balance certainly shifted towards noninvasive strategy Azoulay E. Am J Respir Crit Care Med 2010;182:1038-1046
Possible strategy Clinical suspicion CPIS > 6 (moderate sensitivity) Quantitative cultures Start antibioticics role of biomarkers appears limited after 48-72 hours Diagnosis VAP likely Antibiotics 7-10 D PCT? Diagnosis VAP? Alternative diagnosis? Individual decission TREM- 1 VAP unlikely Stop antibiotics Fagon JY. Crit Care 2011;15:130
Antibiotic duration N = 401 Antibiotics 8 D Antibiotics 15 D 30 28,9 26 20 18,8 17,2 10 13,1 8,7 0 Mortality (%) Antibiotic free days (D) Recurrence (%) Higher relapse rate with pseudomonas and acinetobacter with shorter ab duration Chastre J. JAMA 2003;290:2588-2598
Inhalation antibiotics First Phase II RCT of i.v. versus inhaled ceftazidime and amikacin N = 40 - VAP with susceptible or intermediate pseudomonas strains After 8 dyas of treatment success rate in inhalation group 70% and i.v. 55% (NS) Acquisition of resistance only in i.v. group Lu Q. Am J Respir Crit Care Med 2011;in press
Inhaled antibiotics and MDRO s Double-blind, randomized, placebo-controlled trial (N = 42) MV patients with high risk for MDRO Purulent sputum with + gram stain and CPIS 6 Placebo versus inhaled antibiotics (based on gram stain and/or amikacin) every 8 hrs for 14 D - systemic antibiotics by physician Palmer LB. Am J Respir Crit Care Med 2014;189:1225-1233
Inhaled antibiotics and MDRO s Other MDRO 30 Number tracheal isolates at start 20 10 0 10 13 Control 20 7 Inhaled antibiotics No. of eradicated organisms present at randomization No. of patients with eradication of resistant MO IA Placebo P-value 96% (26/27) 88% (14/16) 9% (2/23) < 0.0001 9% (1/11) < 0.0001 Significantly less development of resistance to systemic antibiotics in inhaled antibiotics group Palmer LB. Am J Respir Crit Care Med 2014;189:1225-1233