Ventilator Associated Pneumonia. ICU Fellowship Training Radboudumc

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1 Ventilator Associated Pneumonia ICU Fellowship Training Radboudumc

2 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

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4 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

5 Incidence of VAP? Prospective cohort & nonrandomized trials (N = 38) Control arms in randomized trials (N = 51) Safdar N. Crit Care Med 2005;33:

6 ICU acquired infection Potential Pathogenic M.O. Reservoir Other patient Digestive tract Surroundings Colonisation Infection

7 Pathophysiology VAP N = 64 Tracheal aspirate 17 PPMO (85%) Gastric aspirate 6 PPMO (20%) Pneumonia N = PPMO Bonten MJ. Chest 1994;105:

8 Exogenous source Oral colonisation Endogenous source Accumulation of secretions above cuff Colonization of Trachea Pneumonia

9 Bed head elevation Niel-Weise BS. Crit Care 2011;15:R111

10 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

11 ET modifications Silver sulfadiazine

12 Subglottic drainage N Control Study P-value Comment Mahul General ICU 29,1 13 < 0,05 No BAL or PSB Valles General ICU 39.6/ /1000 0,03 BAL/PSB Kollef Cardiac ICU 8,2% 5% 0,238 No BAL or PSB Smulders General ICU 16% 4% 0,014 No BAL or PSB Lorente General ICU 22,1% 7,9% 0,001 No BAL or PSB We recently finished a RCT on subglottic drainage after tracheostomy

13 Subglottic drainage 40 Subglottic drainage (n=169) p=0.02 Control (n=164) p=0.01 Incidence, % p= VAP total VAP early VAP late 6 ARR 11% < 5 days 5 days Lacherade JC. Am J Respir Crit Care Med 2010; 182:

14 Lacherade JC. Am J Respir Crit Care Med 2010; 182: Secondary outcomes , ,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

15 Subglottic drainage Reduces LOS and duration of MV but not mortality Muscedere J. Crit Care Med 2011

16 SDD and SOD NS 30 NS 27,5 26,6 26,9 Crude mortality (%) 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

17 Colonisation with resistant Gr- organisms 20 Ceftazidime - rectal isolates % colonised Time (months) 24Oostdijk EAN. Am J Respir Crit Care Med 2010;181:

18 Colonisation with BMRO de Smet AMGA. Lancet Inf Dis 2011

19 Oral decontamination and antibiotic resistance SDD SOD 30 P < P < 0.42 P < ,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 = In both groups gradual resistance increase Oostdijk EAN. JAMA 2014

20 SDD Meta-analysis SOD Chlorhexidine ( ) Favours SOD Favours Control ( ) ( ) Favours SDD Favours Control Favours SDD Favours Control Price R. BMJ 2014;348:g2197

21 Morrow LE. Am J Respir Crit Care Med 2010;182: Probiotics and VAP prevention RCT - N = oral/gastric Lactobaccilus rhamnosus 40 Probiotics Control P = P = VAP 0 Closttridium Difficile

22 Early vs late tracheotomy for VAP prevention N = 419 Early = 6-8 D Late = D Early Late P = VAP % 0 MV free days D 28 No difference in mortality JAMA 2010;303:

23 69% 57%

24 Diagnostic strategy in oncology patients with ARF Azoulay E. Am J Respir Crit Care Med 2010;182:

25 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:

26 Possible strategy Clinical suspicion CPIS > 6 (moderate sensitivity) Quantitative cultures Start antibioticics role of biomarkers appears limited after 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

27 Antibiotic duration N = 401 Antibiotics 8 D Antibiotics 15 D 30 28, ,8 17, ,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:

28 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

29 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:

30 Inhaled antibiotics and MDRO s Other MDRO 30 Number tracheal isolates at start 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) < % (1/11) < Significantly less development of resistance to systemic antibiotics in inhaled antibiotics group Palmer LB. Am J Respir Crit Care Med 2014;189:

31 Aspergillus infection Bimodal peak During mucosal breakdown/prolonged granulocytopenia and during treatment for GVHD 1 year incidence after allogeneic HSCT of 12% and mortality of 50-80% Positive culture of tracheal aspirate and/or BAL + antigen rise sufficient to start empirical treatment in right clinical/ radiological circumstances

32 Epidemiology (1) Increased use of HSCT practices with high risk of GVHD (HLA mismatch and reduced intensity conditioning) T-cell-depleted and CD34-selected stem cells reduce GVHD but have higher risk of delayed immune reconstitution Antifungal prophylaxis in preengraftment period Fewer early fungal infections - increasing late infections

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34 Epidemiology (2) Classical radiological signs in neutropenic patients are now often absent Serum galactomannan test less sensitive in non-neutropenic patients Increased incidence of non-aspergillus moulds

35 Nodular infiltrate Halo sign

36 Aspergillus after H1N1 N = 40 Proven H1N1 infection in the ICU N = 31 (77%) No Invasive Pulmonary Aspergillosis N = 9 (23%) Invasive Pulmonary Aspergillosis Proven N = 5 Probable N = 5 Use of corticosteroids significant risk factor Wauters J. Intensive Care Med 2012;38:

37 Cerebral aspergillosis in ICU patients AspICU study (563 adult patients with + direct Asp test on any body site) N = 10 (1.8%) - none primarily diagnosed with invasive sinus or pulmonary aspergillosis Often multiple lesions - none of the patients had neurological signs One patient extensive meningitis Mortality 9/10 despite antifungal treatment Spapen H. Int J Antimicrob Agents 2014;43:

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39 Conclusions Gold standard diagnostic strategy still unclear - Role of biomarkers limited Invasive strategy in immunocompromised patients may be unnecessary Prevention of tracheal colonisation apparently successful Role of inhaled antibiotics still unclear