VAP- Ventilator associated pnemonia.pptx

Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation. It typically develops more than 48 hours after intubation and is a significant cause of morbidity and mortality in critically ill patients.

1. Ventilator Associated Pneumonia Dr Mohammad Abbas MBBS,MD, DrNB (Critical Care Medicine) Kauvery Hospital, Bangalore

2. CASE A 52-year-old female admitted with left pontine infarct was being ventilated for Type 1 respiratory failure for the past 6 days. She was not on any antibiotics and seemed to be improving. She becomes febrile overnight ( 102ᴼF ). How will you approach this patient?

3. CASE CONTINUED.. Chest X Ray Patient is being required higher FiO 2 to maintain P/F ratio. What are your differentials ?

4. DIFFERENTIALS DIAGNOSIS RADIOLOGICAL FEATURES PNEUMONIA/ CONSOLIDATION Unilateral or bilateral parenchymal opacity, with air bronchogram . Lobar anatomy in Lobar pneumonia Diffuse distribution of opacities in bronchopneumonia COLLAPSE Complete opacification of airspace, associated with features of volume loss such as rib crowding, lobar opacification without air bronchogram , mediastinal shift to the same side , and elevation of the diaphragm PULMONARY EMBOLISM Non-specific atelectasis with an elevation of the hemidiaphragm Peripheral wedge-shaped pulmonary infarct Dilatation of the pumonary artery

5. PULMONARY EDEMA B/L interstitial and alveolar edema , spreading from the center to the periphery, cardiomegaly , prominent upper zone markings, Kerley B Lines , Bilateral symmetrical pleural effusion which can be mild to moderate RE-EXPANISON PULMONARY EDEMA Interstitial edema involving the affected hemithorax . No cardiomegaly or signs of CCF PLEURAL EFFUSION U/L or B/L uniform opacity, with no air bronchogram , with mediastinal shift to the opposite side PARENCHYMAL FIBROSIS Interstitial thickening with associated volume loss, U/L or B/L. H/O any specific drugs, irradiation or comparison with previous radiology BOOP, PULMONARY HAEMORRHAGE, EOSINOPHILIC PNEUMONIA, DRUG INDUCED PARENCHYMAL DISEASE BOOP- Peripheral patchy consolidation Non-specific , diffuse patchy alveolar infiltrates not limited to lobar anatomy Eosinophilic pneumonia- Reverse pulmonary edema

6. What is it? On Ventilator More than 6 days New onset fever New changes in the LUNG Provisional diagnosis - VAP

7. DEFINITION Hospital-acquired pneumonia (HAP) is defined by an infection of the lung parenchyma that occurred at least 48 hours after hospital admission. Ventilator-associated pneumonia (VAP) develops in intensive care unit (ICU) patients mechanically ventilated for at least 48 hours  . Classified into : Early onset (within the first 96 hours of MV) and Late onset (more than 96 hours after the initiation of MV), which is more commonly attributable to multidrug–resistant pathogens Ventilator-associated tracheobronchitis (VAT) is characterized by signs of respiratory infection without new radiographic infiltrates in a patient mechanically ventilated for at least 48 hours 7

8. Ventilator-Associated Pneumonia Ventilator-associated pneumonia (VAP) can develop in any patient on a ventilator 1 1 Centers for Disease Control. VAP FAQs. http://www.cdc.gov/HAI/vap/vap_faqs.html. Accessed June28, 2019. 2 Krein SL, Kowalski CP, Damschroder L, et al. Infect Control Hosp Epidemiol . 2008;29:933-40. 3 Tedja R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/ health-care-associated-pneumonia. Accessed June28, 2019. VAP is the most common of the hospital-acquired infections (HAI) in the intensive care unit (ICU) 2,3 Onset of VAP Intubation or mechanical ventilation 24 Hrs 48 Hrs 72 Hrs 8

9. Ventilator-Associated Pneumonia: Characterization Presence of a new or progressive infiltrate Signs of systemic infection (fever, altered white blood cell count) Changes in sputum characteristics Detection of a causative agent Onset of VAP Intubation or mechanical ventilation 24 Hrs 48 Hrs 72 Hrs American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med.  2005;171:388-416. 9

10. Risk Factors Rello J, Ollendorf DA, Oster G, et al. Chest.  2002;122(6):2115-21. Duration of intubation Male gender Trauma admission Severity of illness Prior use of antibiotics Supine positioning Prior use of H2 blockers ℞ ICU + 10

11. Methods of Contamination 1 Tedja R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/health-care-associated-pneumonia. Accessed June28, 2019. Inoculation during the intubation process Contaminated aerosol or ventilator condensate Endotracheal tube biofilm Aspiration from sinus, oropharyngeal, or gastric fluids around the tube 11

12. Microbe Types Polymicrobial Centers for Disease Control. VAP FAQs. http://www.cdc.gov/HAI/vap/vap_faqs.html. Accessed April 6, 2014. Krein SL, Kowalski CP, Damschroder L, et al. Infect Control Hosp Epidemiol . 2008;29:933-40. Tedja R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/health-care-associated-pneumonia. Accessed June28, 2019. Combes A, Figliolini C, Trouillet J, et al. Chest.  2002;121(5):1618-23. Bacteria Gram negative bacteria are the most common type seen in VAP May be gram positive during MRSA outbreak Viruses Not as common as bacterial causes, may be seen in immunodeficient patients Fungi Occasionally seen in immunodeficient patients, rarely causative Monomicrobial Only one pathogen type Most common VAP infection type Multiple pathogens 12

13. Bacteria Associated With VAP Sader HS, Rhomberg PR, Farrell DJ, et al. Antimicrob Agents Chemother . 2015;59(6):3263-70. 13

14. VAP Increases Length of Stay and Ventilation Duration Restrepo M, Anzueto A, Arroliga A, et al. Infect Control Hosp Epidemiol . 2010;31(5):509-15. Median Number of Days (Range) Type of Patient and Variable Case Patients (N = 30) Control Patients (N = 90) P -Value All patients Intubation duration* 10.1 (3-25) 4.7 (1-22) < 0.001 VAP onset ≤ 4 days 9.1 (3-20) VAP onset > 4 days 12.9 (5-25) Intensive care unit LOS 18.5 (5-33) 8 (2-33) < 0.001 VAP onset ≤ 4 days 11.5 (5-29) VAP onset > 4 days 23.5 (6-33) Hospital LOS 26.5 (5-36) 14 (3-50) < 0.001 VAP onset ≤ 4 days 18.5 (5-31) VAP onset > 4 days 31.5 (20-36) Survivors** Intubation duration 10.2 (3-25) 4.8 (1-22) < 0.001 Intensive care unit LOS 19 (5-33) 8 (2-33) < 0.001 Hospital LOS 29 (12-36) 16 (3-50) < 0.001 * Duration after VAP onset; ** There were 25 case patients and 61 control patients who survived. 14

15. Hospital Costs Due to increased length of stay and ventilator time, hospital costs are also increased with VAP 1-2 Incremental costs associated with VAP have been estimated. 1 Koenig SM, Truwit JD. Clin Microbiol Rev . 2006;19(4):637-57. 2 Restrepo M, Anzueto A, Arroliga A, et al. Infect Control Hosp Epidemiol . 2010;31(5):509-15. Median Total Hospital Costs 2 P < 0.01 15

16. EPIDEMIOLOGY 16

17. Systematic Review of VAP in Asia • CID 2019:68 (1 February)

18. EPIDEMIOLOGY OF VAP Systematic Review of VAP in Asia • CID 2019:68 (1 February)

19. MORTALITY Crude mortality rates for VAP are 10-40% 1 VAP increases mortality of ventilated patients up to 50% compared to ventilated patients without VAP (32%) 2-3 Mortality rates are lower in long term acute care hospitals (~15%) 4 1 Cocanour CS, Peninger M, Domonoske BD, et al. J Trauma. 2006;61:122-30. 2 Al-Tawfiq JA, Abed MS. Am J Infect Control. 2010;38:552-6. 3 Kalanuria AA, Ziai W, Mirski M. Crit Care. 2014;18:208. 4 American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171:388-416. 19 10-50% ~15% VAP Mortality (%) Long Term Acute Care General Hospital

20. Infect. Control Hosp. Epidemiol . 2016;37(2):172–181

21. GUIDELINES AND RECOMMENDATIONS 21

22. Guidelines In 2011 the CDC convened a Working Group for VAP and other ventilator-associated events (VAE) CDC. Device Associated Module . 2019. VAE surveillance definition algorithm implemented in 2013 Based on objective, streamlined, and potentially automatable criteria that identify a broad range of conditions and complications occurring in mechanically-ventilated adult patients There are three definition tiers within the VAE algorithm Ventilator-Associated Condition (VAC) Infection-related Ventilator-Associated Complication (IVAC) Possible and probable VAP 22

23. CDC VAE Algorithm (CENTRE OF DISEASE CONTROL AND PREVETION) CDC. Device Associated Module . 2019. Infection-related Ventilator-Associated Complication 23 After a period of stability or improvement on the ventilator, the patient has at least one of the following indicators of worsening oxygenation: 1 ) Increase in daily minimum* FiO2 of ≥ 0.20 (20 points) over the daily minimum FiO2 in the baseline period, sustained for ≥ 2 calendar days . 2) Increase in daily minimum* PEEP values of ≥ 3 cmH2O over the daily minimum PEEP in the baseline period†, sustained for ≥ 2 calendar days . Patient has a baseline period of stability or improvement on the ventilator, defined by ≥ 2 calendar days of stable or decreasing daily minimum* FiO2 or PEEP values . The baseline period is defined as the 2 calendar days immediately preceding the first day of increased daily minimum PEEP or FiO2. *Daily minimum defined by lowest value of FiO2 or PEEP during a calendar day maintained for at least 1 hour. On or after calendar day 3 of mechanical ventilation and within 2 calendar days before or after the onset of worsening oxygenation, the patient meets both of the following 2 criteria: 1 ) Temperature > 38 °C or < 36°C , OR white blood cell count ≥ 12,000 cells/mm3 or ≤ 4,000 cells/mm3 . AND 2) A new antimicrobial agent(s) is started , and is continued for ≥ 4 calendar days. Ventilator-Associated Condition †Daily minimum PEEP values of 0-5 cmH2O are considered equivalent for the purposes of VAE surveillance.

24. Possible Ventilator-Associated Pneumonia On or after calendar day 3 of mechanical ventilation and within 2 calendar days before or after the onset of worsening oxygenation, ONE of the following criteria is met: 1) Criterion 1: Positive culture of one of the following specimens, meeting quantitative or semi-quantitative thresholds as outlined in protocol, without requirement for purulent respiratory secretions: Endotracheal aspirate- ≥ 10 5 CFU/mL or corresponding semi-quantitative result; bronchoalveolar lavage- ≥ 10 4 CFU/mL or corresponding semi-quantitative result; lung tissue- ≥ 10 4 CFU/g or corresponding semi-quantitative result; protected specimen brush -≥ 10 3 CFU/mL or corresponding semi-quantitative result 2) Criterion 2: Purulent respiratory secretions (defined as secretions from the lungs, bronchi, or trachea that contain > 25 neutrophils and < 10 squamous epithelial cells per low power field [ lpf , x100]) plus organism identified from one of the following specimens (to include qualitative culture, or quantitative/semi-quantitative culture without sufficient growth to meet criterion #1): Sputum, endotracheal aspirate, bronchoalveolar lavage, lung tissue, protected specimen brush 3) Criterion 3: One of the following positive tests: Organism identified from pleural fluid (where specimen was obtained during thoracentesis or initial placement of chest tube and NOT from an indwelling chest tube); lung histopathology, defined as: 1) abscess formation or foci of consolidation with intense neutrophil accumulation in bronchioles and alveoli; 2) evidence of lung parenchyma invasion by fungi (hyphae, pseudohyphae or yeast forms); 3) evidence of infection with the viral pathogens listed below based on results of immunohistochemical assays, cytology, or microscopy performed on lung tissue; diagnostic test for Legionella species; diagnostic test on respiratory secretions for influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus, rhinovirus, human metapneumovirus , coronavirus CDC VAE Algorithm CDC. Device Associated Module . 2019. Infection-related Ventilator-Associated Complication 24

25. Diagnostics and Point-of-Care 25

26. Diagnostic Methods Diagnosing VAP requires a high clinical suspicion combined with bedside examination and microbiologic analysis of respiratory secretions.  CDC. Device Associated Module . 2019. 26

27. VAP Clinical Criteria Johanson Criteria Presence of a new or progressive radiographic infiltrate Plus at least two of three clinical features: Fever > 38 º C Leukocytosis or leukopenia Purulent secretions Koenig SM, Truwit JD. Clin Microbiol Rev . 2006;19(4):637-57. Rea- Neto A, Cherif M, Youssef N, et al.  Critical Care.  2008;12:R56.  Accepted clinical criteria for pneumonia are of limited diagnostic value in definitively establishing the presence of VAP. 27

28. VAP Clinical Criteria ARDS = acute respiratory distress syndrome Rea- Neto A, Cherif M, Youssef N, et al.  Critical Care.  2008;12:R56.  VAP Score > 6 Clinical Pulmonary Infection Score (CPIS) Temperature Oxygenation (PaO2/FiO2) Tracheal Secretions (Score) 0 point: 36.5–38.4ºC 0 point: > 240 or ARDS 0 point: no secretions 1 point: 38.5–38.9ºC 2 points: < 240, No evidence of ARDS 1 point: Abundant 2 points: < 36 or > 39ºC 2 points: Purulent sputum Blood leukocytes (Cells/ μ L) Pulmonary Radiography Tracheal Aspirate Culture 0 point: 4000–11000 0 point: No infiltrate 0 point: Minimal growth 1 point: < 4000 or > 11000 1 point: Diffuse or patchy infiltrates 1 point: Moderate or more growth 2 points: > 500 band forms 2 points: Localized infiltrate 2 points: Moderate or greater growth 28 Modified CPIS (MCPIS): 2 components were revised: Oxygenation (PaO2/FiO2) and Sputum description

29. Microbiological Methods Bronchoalveolar lavage Protected specimen brush Endotrachial aspirate Lung tissue CDC. Device Associated Module . 2019. 29

30. The European guidelines indicate that it is preferable to obtain the distal quantitative samples before antibiotic treatment , since it is known that if samples are obtained within 48 h of the start of antibiotic treatment the result may be altered or emerge as negative. PNEUMONIA | A. TORRES ET AL. ,ERJ Open Res 2018; 4

31. Biomarkers Microbiological techniques can take up to 48 hours 1 Current biomarkers have not been completely evaluated without prior antibiotic use 2 Previous use of antibiotics may give false-negatives 1 Identification of biomarkers may eliminate disadvantages of common VAP diagnostic techniques 1-2 Procalcitonin sTREM-1 C-reactive protein MR- proADM 1 Ramirez P, Garcia MA, Ferrer M, et al. Eur Respiratory J . 2008;31:356-62. 2 Palazzo SJ, Simpson T, Schnapp L. Heart Lung . 2011;40(4):293-8. 31

32. CRP Shows Promise for VAP Prediction OR 95% CI P -value Adjusted OR 95%CI P -value Slope CRP (mg/ dL ) 1.641 1.229--2.192 < 0.001 1.624 1.206–2.189 0.001 CRP ratio 1.516 1.021–2.250 0.039 1.48 1.060–2.067 0.021 PCT (μ g/L) 0.803 0.544–1.183 0.267 0.844 0.559–1.274 0.419 ADM ( nmol /L) 0.74 0.147–3.742 0.716 0.73 0.137–3.902 0.713 WCC (x10 3 /mm 3 ) 1.182 0.807–1.729 0.391 1.225 0.809–1.855 0.338 Temperature (°C) 0.288 0.033–2.540 0.262 0.27 0.028–2.590 0.256 Highest CRP (mg/ dL ) 1.044 1.000–1.090 0.052 1.037 0.992–1.085 0.11 CRP ratio 1.201 1.065–1.355 0.003 1.202 1.061–1.363 0.004 PCT (μ g/L) 1.032 0.987–1.079 0.168 1.02 0.974–1.068 0.392 ADM ( nmol /L) 1.335 1.022–1.744 0.034 1.369 1.035–1.809 0.028 WCC (x10 3 /mm 3 ) 1.032 0.987–1.079 0.168 1.02 0.974–1.068 0.392 Temperature (°C) 2.043 1.170–3.536 0.012 2.053 1.126–3.744 0.019 Δ max CRP (mg/ dL ) 1.151 1.057–1.252 0.001 1.139 1.039–1.248 0.006 CRP ratio 1.213 1.030–1.428 0.021 1.186 1.018–1.381 0.029 PCT (μ g/L) 1.036 0.984–1.089 0.178 1.023 0.971–1.078 0.399 ADM ( nmol /L) 1.395 0.964–2.020 0.078 1.372 0.943–1.996 0.099 WCC (x10 3 /mm 3 ) 1.044 0.963–1.131 0.294 1.046 0.959–1.140 0.312 Temperature (°C) 1.02 0.665–1.565 0.928 0.933 0.583–1.494 0.772 Variables included in the adjusted model: age, sex, SAPS II, cause of admission. CRP C-reactive protein, ADM MR - proADM mid-region fragment of pro- adrenomedullin , OR odds ratio, PCT procalcitonin, WCC white cell count Póvoa P, Martin‑ Loeches I, Ramirez P, et al. Ann Inten Care. 2016;6:32. 32

33. CRP and Modified CPIS Scores Are Associated With Gradual Development of VAP AUC 95%CI P -Value Sensitivity Specificity Likelihood Ratio Positive Negative PCT ≥ 0.5 ng/mL 0.505 0.332–0.677 0.953 65 40 1.08 0.88 CRP ≥ 54 mg/ dL 0.678 0.493–0.863 0.047 60 49 1.22 0.86 mCPIS > 5 points 0.67 0.545–0.796 0.016 44 92 6.67 0.6 CRP=C-reactive protein, mCPIS =modified Clinical Pulmonary Infection Score, PCT= procalcitonin Ramirez P, Lopez- Ferraz C, Gordon M, et al. Critical Care. 2016;20:169. 33

34. Change in PCT Associated With VAP Mortality Tanrıverdi H, Tor MM, Kart L, et al. Ann Thorac Med . 2015;10(2):137-42. P -values Survivor vs. Non-survivor Variables Δ Day 0-3 Δ Day 0-7 Δ Day 3-7 PCT 0.005 0.049 0.824 CRP 0.247 0.057 0.859 CRP=C-reactive protein, PCT= procalcitonin Relationship Between Prognosis and Kinetics of PCT and CRP Levels 34

35. Rapid Diagnostics and Point-of-Care Point-of-care bacterial PCR Methicillin-resistant Staphylococcus aureus Methicillin-susceptible Staphylococcus aureus Actinobacter baumannii Pseudomonas aeruginosa Good negative predictive value Cost effective Leone M, Malavieille F, Papazian L, et al. Critical Care.  2013;17:R170.   Rice LM, Reis AH, Mistry R, et al. J Appl Microbiol . 2013;115:818-27. 35

36. DAB: Dynamic Airbronchogram , FB: Fluid Bronchogram , SAB: Static Airbrochogram , SP-CD: small subpleural consolidation 36 a: Subpleural hypoechogenic or tissue-like area b: In all patients included in study c: only in patients with signs of ventilator-associated pneumonia d: in each patient Staub et al.

37. Treatment of VAP Initial antibiotic choice Presence of shock Possible risk factors for MDR pathogens. MDR risk factors: Immunosupressed patient Hospital stay >/=5 days currently Antibiotic use in prior 90 days. High frequency of resistance in ICU (>25%). HAP risk factors.

38. Treatment of VAP issues Antibiotic choice Single antibiotic Vs combination. Antibiotics with good lung penetration. Short duration Vs long duration. Role of biomarkers and cultures in de-escalation. Other modes of administration.

39. TREATMENT Recommendations (IDSA 2016): Should Selection of an Empiric Antibiotic Regimen for VAP Be Guided by Local Antibiotic-Resistance data? TREATMENT OF VAP Hospitals regularly generate and disseminate a local antibiogram , specific to their intensive care population(s) if possible. Empiric treatment regimens by the local distribution of pathogens associated with VAP and their antimicrobial susceptibilities . IDSA 2016

40. What Antibiotics Are Recommended for Empiric Treatment of Clinically Suspected VAP? Coverage for S. aureus , Pseudomonas aeruginosa , and other gram-negative bacilli in all empiric regimens i . Active against MRSA for the empiric treatment of suspected VAP only in patients with any of the following: Risk factor for antimicrobial resistance, Patients treated in units where >10%–20% of S. aureus isolates are methicillin resistant, and Patients in units where the prevalence of MRSA is not known ii. Active against methicillin sensitive S. aureus (MSSA) (and not MRSA) for the empiric treatment of suspected VAP in patients without risk factors for antimicrobial resistance, where <10%–20% of S. aureus isolates are methicillin resistant. IDSA 2016

41. Empiric coverage for MRSA either vancomycin or linezolid . Empiric treatment coverage for MSSA (and not MRSA), a regimen including piperacillin-tazobactam , cefepime , levofloxacin , imipenem , or meropenem . Two antipseudomonal antibiotics from different group of antibiotics in patients with any of the following: Risk factor for antimicrobial resistance , Patients in units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy , and Patients in an ICU where local antimicrobial susceptibility rates are not available What Antibiotics Are Recommended for Empiric Treatment of Clinically Suspected VAP? IDSA 2016

42. One antibiotic active against P. aeruginosa for the empiric treatment of suspected VAP in patients without risk factors for antimicrobial resistance where ≤10% of gram-negative isolates are resistant to the agent being considered for monotherapy Avoiding aminoglycosides if alternative agents with adequate gram-negative activity are available Avoiding colistin if alternative agents with adequate gram-negative activity are available What Antibiotics Are Recommended for Empiric Treatment of Clinically Suspected VAP? IDSA 2016

43. Should Selection of an Empiric Antibiotic Regimen for HAP (Non-VAP) Be Guided by Local Antibiotic Resistance Data? Generate and disseminate a local antibiogram , tailored to their HAP population, if possible. Empiric antibiotic regimens be based upon the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities IDSA 2016

44. What Antibiotics Are Recommended for Empiric Treatment of Clinically Suspected HAP (Non-VAP)? Empirically for HAP , activity against S. aureus . HAP who are being treated empirically, antibiotics with activity against P. aeruginosa and other gram-negative bacilli. IDSA 2016

45. What Antibiotics Are Recommended for Empiric Treatment of Clinically Suspected HAP (Non-VAP)?

46. PNEUMONIA | A. TORRES ET AL. ,ERJ Open Res 2018; 4