VENTILATOR ASSOCIATED PNEUMONIA 4/11/2017 11:15 PM VENTILATOR ASSOCIATED PNEUMONIA Prof. dr. Ioana Grigoras University of Medicine and Pharmacy Regional Institute of Oncology Anesthesia and Intensive Care Dept. Iasi, Romania © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

VAP It is the second most common nosocomial infection in the ICU VAP occurs in 9–27 % of all mechanically ventilated patients, with the highest risk being early in the course of hospitalization Melsen WG, et al.Lancet Infect Dis 2013, 13:665–671

VAP - incidence 9.7% (38 prospective studies - 48 112 patients) 3 - 40% The variability of the observed incidence the variability of diagnostic techniques used and to a lesser extent by the variability of prevention process. Current Opinion in Critical Care 2011,17:464–471

VAP - mortality The attributable mortality for VAP - earlier studies 33–50 % - more recent studies 9–13 % Melsen WG, et al.Lancet Infect Dis 2013, 13:665–671

VAP - mortality Current Opinion in Critical Care 2011,17:464–471

VAP - mortality The attributable mortality of VAP is 6–8% The PIRO concept: Predisposition: ↑ admission severity scores - intermediate ↓in trauma patients Infection: ↑ in case of bacteremic VAP late-onset VAP inappropriate antimicrobial treatment Response: ↑in case of shock Organ: ↑ according to the severity of organ failures Current Opinion in Critical Care 2011,17:464–471

VAP is common, morbid, and preventable.

VAP a quality-of-care indicator for ICUs. In the United States, VAP was recently proposed as a quality-of-care indicator for ICUs.

VAP - definition Pneumonia that occurs 48–72 hours or thereafter following endotracheal intubation, characterized by the presence of a new or progressive infiltrate, signs of systemic infection, changes in sputum characteristics, and detection of a causative agent. American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416

VAP - definition VAP definitions are complicated, labor intensive, highly subjective, and nonspecific. Current Opinion in Critical Care 2011,17:464–471

VAP - pathogenesis exogenous endogenous

VAP - pathogeny Infectious bacteria obtain direct access to the lower respiratory tract: microaspiration development of a biofilm laden with bacteria within the ENT pooling and trickling of secretions around the cuff impairment of mucociliary clearance of secretion

VAP – risk factors Pathogenic material from surrounding anatomic structures: stomach, sinuses, nasopharynx and oropharynx Reintubation following extubation Severity of underlying disease American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416 Hunter JD. BMJ 2012, 344(e3325):e3325 Rocha LA, et al. Am J Infect Control 2013, 41:1236–1240

VAP – risk factors Previous surgery Antibiotic exposure Critically ill patients may have impaired phagocytosis and behave as functionally immunosuppressed American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416 Conway Morris A et al. Br J Anaesth 2013, 3:1–10

Everyone has some level of risk Critically ill patients Postsurgical patients Trauma patients Burn patients Immunocompromised Patients with indwelling devices Nursing home residents Neonates Children Previously healthy Who is at risk? There are several at risk groups, including those shown here. With all the at-risk groups early recognition is still a problem. This maybe due to masking of signs and symptoms by other conditions or especially the healthy individuals when the index of suspicion for this diagnosis is too low. The ideal biomarker could help clinicians recognize sepsis earlier. Other statistics to keep in mind: 3 cases/1000 total population Risk rises with age Incidence is increasing as the population ages Rate is increasing ~ 1.5% per year 55% of septic patients have a significant comorbidity: 12.3% COPD 11.6% nonmetastatic neoplasm 6.3% HIV 5.3% metastatic neoplasm 43% mortality associated with sepsis and metastatic neoplasm 15

VAP - pathogens Bacteria causing early-onset VAP: Streptococcus pneumoniae Hemophilus influenzae Methicillin-sensitive staphylococcus aureus Antibiotic-sensitive enteric Gram-negative bacilli: Escherichia coli Klebsiella pneumonia Enterobacter species Proteus species Serratia marcescens American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416

VAP - pathogens Bacteria causing late-onset VAP : Methicillin-resistant S. aureus Acinetobacter Pseudomonas aeruginosa Extended-spectrum beta-lactamase producing bacteria (ESBL) The exact prevalence of MDR organism is variable between institutions and also within institutions American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416

VAP - diagnosis Kalanuria et al. Critical Care 2014, 18:208

VAP - diagnosis There is no universally accepted, gold standard diagnostic criterion for VAP Clinical pulmonary infection score (CPIS) - between 0 and 12 A score of ≥ 6 - good correlation with the presence of VAP A metaanalysis of 13 studies evaluating the accuracy of CPIS: sensitivity 65% and specificity 64% (95% CI 60–67%) National Healthcare Safety Network (NHSN) July 2013 CDC/NHSN Protocol Clarifications Shan J, Chen HL, Zhu JH: Respir Care 2011, 56:1087–1094

VAP - diagnosis Lack of accuracy is compounded by subjectivity. Traditional VAP definitions include criteria such as ‘new or progressive infiltrates,’ ‘change in the character of the sputum,’ ‘increased suctioning requirements,’ ‘worsening oxygenation’. Surveyors are typically left to apply these criteria using their own discretion. Curr Opin Crit Care 2013, 19:424–431

VAP - diagnosis Clinical diagnosis is neither sensitive nor specific for VAP OVERDIAGNOSIS Up to 50% of patients who fulfilled clinical criteria for VAP do not have histological evidence of pneumonia at autopsy Most patients rather have one or more different conditions including: acute respiratory distress syndrome (ARDS), pulmonary edema, thromboembolic disease, malignancy, hemorrhage, contusion, atelectasis, pneumonitis, a.o. UNDERDIAGNOSIS Clinical criteria for VAP miss about a third of patients who do have pneumonia Curr Opin Crit Care 2013, 19:424–431

VAP - diagnostic bronchoscopic examination bronchoalveolar lavage Diagnostic procedures based on bronchoscopic examination bronchoalveolar lavage protected specimen brush are more specific than a diagnosis based on clinical findings and a tracheal aspirate.

VAP - diagnosis Lower respiratory tract samples for culture/microbiology The ATS and the IDS of America guidelines recommendation Quantitative cultures BAL techniques (BAL, mini-BAL or PSB) the diagnostic threshold 103 cfu/ml for protected specimen brushing 104 cfu/ml for BAL Canadian Clinical Trials - similar clinical outcomes - similar overall use of antibiotics BAL with quantitative culture endotracheal aspiration with non-quantitative culture American Thoracic Society, Infectious Diseases Society of America: Am J Respir Crit Care Med 2005, 171:388–416 Canadian Critical Care Trials Group.N Engl J Med 2013,355:2619–2630

VAP – molecular diagnosis MOLECULAR DIAGNOSTIC METHODS Nucleic acid-based amplification methods the most commonly used in the molecular diagnosis of infectious diseases The reference method for the microbiological diagnosis of some respiratory pathology surpassing other conventional procedures The molecular technologies – multiple target detection systems (or multiplex assays) using the nucleic acids amplification by PCR, most frequently multiplex real-time PCR Curr Opin Crit Care 2012, 18:487–494

VAP – molecular diagnosis NEW PLATFORMS novel multiplex platforms directed at respiratory infections most of them the microorganisms target - only viruses/ combination viruses+bacteria related to the community-acquired respiratory tract infection involving adults, pediatric or immunocompromised patients ADVANTAGES to provide results within a few hours direct respiratory samples the ability to detect multiple targets leading to the identification and antimicrobial resistance simultaneously quantitative results Curr Opin Crit Care 2012, 18:487–494

VAP – positive airway cultures Always VAP ?

VAP – positive airway cultures Tareq Abu-Salah et al, Adv Ther, 2011

VAP - diagnostic “possible pneumonia”: patients with an IVAC and purulent secretions alone or pathogenic cultures alone “probable pneumonia”: those with both purulent secretions and positive quantitative or semiquantitative cultures Chest radiograph findings have been excluded in the new criteria because of their subjectivity National Healthcare Safety Network (NHSN) July 2013 CDC/NHSN Protocol Clarifications

VAP - surveillance VAP surveillance - ?!? Surveillance for complications in general rather than pneumonia in particular gives a more complete picture of the population of patients who suffer significant adverse events on mechanical ventilation. Current Opinion in Critical Care 2011,17:464–471

Ventilator-associated events Curr Opin Crit Care 2013, 19:424–431

Ventilator-associated events A ventilator-associated condition (VAC) ≥2 days of stable or decreasing daily minimum positive end expiratory pressure (PEEP) or daily minimum fraction of inspired oxygen (FiO2) followed by an increase in daily minimum PEEP by at least 3cmH2O sustained for ≥2 days or in daily minimum FiO2 by ≥20 points sustained for at least ≥2 days National Healthcare Safety Network (NHSN) July 2013 CDC/NHSN Protocol Clarifications

Ventilator-associated events Infection-related ventilator-associated complications (IVAC) VAC + concurrent inflammatory signs at least 4 days of new antibiotics. National Healthcare Safety Network (NHSN) July 2013 CDC/NHSN Protocol Clarifications

Ventilator-associated events Possible pneumonia (possible VAP) IVAC + purulent secretions alone or pathogenic cultures alone Probable pneumonia (probable VAP) both purulent secretions and positive quantitative/semiquantitative cultures Chest radiograph findings have been excluded in the new criteria because of their subjectivity National Healthcare Safety Network (NHSN) July 2013 CDC/NHSN Protocol Clarifications

Ventilator-associated events VAC IVAC Probable pneumonia Curr Opin Crit Care 2013, 19:424–431

Ventilator-associated events ADVANTAGES: it circumvents the difficulty in diagnosing VAP it broadens the focus of safety surveillance and prevention includes multiple complications of mechanical ventilation it allows for simple definitions based on changes in patients’ ventilator settings, it facilitates purely quantitative, objective definitions amenable to automation and hence more suitable for benchmarking. Curr Opin Crit Care 2013, 19:424–431

VAP - treatment The major goals of VAP management early, appropriate antibiotics in adequate doses followed by de-escalation based on microbiological culture results and the clinical response of the patient. Antimicrobial stewardship programs optimize antibiotic selection, dose, and duration to increase efficacy in targeting causative pathogens

VAP - treatment Kalanuria et al. Critical Care 2014, 18:208

VAP - treatment Kalanuria et al. Critical Care 2014, 18:208

Microbiology HCAP (n=199) HAP (n=379) VAP (n=606) Gram-positive pathogens, n (%) 116 (58.3) 223 (58.8) 441 (72.8) MRSA 81 (40.7) 124 (32.7) 258 (42.6) MSSA 12 (6.0) 51 (13.5) 107 (17.7) Pneumococcus 4 (2.0) 10 (2.6) 15 (2.5) Other Streptococcus spp. 7 (3.5) 16 (4.2) 19 (3.1) Gram-negative pathogens, n (%) 52 (26.1) 112 (29.6) 220 (36.3) Pseudomonas aeruginosa 22 (11.1) 27 (7.1) 57 (9.4) Acinetobacter spp. 8 (4.0) 15 (4.0) 44 (7.3) Haemophilus spp. 6 (3.0) 5 (1.3) 23 (3.8) Moraxella catarrhalis 1 (0.3) 2 (0.3) Klebsiella spp. 5 (2.5) 31 (8.2) 40 (6.6) Escherichia coli 9 (4.5) 19 (5.0) 17 (2.8) Enterobacter spp. 3 (1.5) 15 (3.9) 31 (5.1) Proteus mirabilis 1 (0.5) 8 (2.1) 13 (2.1) Stenotrophomonas maltophilia 2 (0.5) 12 (2.0) Polymicrobial, n (%) 110 (55.3) 187 (49.3) 383 (63.2) Culture negative, n (%) 103 (27.2) 80 (13.2) Bacteremia, n (%) 28 (14.1) 49 (12.9) 103 (70.0) Kett DH et al. Poster presented at: 51st ICAAC; 17-20 September 2011; Chicago

Gram-positive VAP - treatment Kollef MH, et al. Intensive Care Med. 2004;30:388-94

VAP – antibiotic tissue penetration Vancomycin Teicoplanin Linezolid Bone 7-13% 50-60% 60% Central nervous system 0-18% 10% 70% Epithelial lining fluid 11-17% 30% 450% Inflammatory fluid 77% 104% Muscle 40% 94% Peritoneal dialysis fluid 20% 61% Graziani 1988, Matzke 1986, Albanese 2000, Georges1997, Lamer 1993, Daschner 1987, Blevins 1984, Wilson 2000, Stahl 1987, Wise 1986, Franck 1997, Lovering 2002, Conte 2002, Gee 2001,Gendjar 2001

VAP - treatment Kalanuria et al. Critical Care 2014, 18:208

KPC “Tsunami”

VAP - treatment Kalanuria et al. Critical Care 2014, 18:208

VAP – antibiotic policy

VAP – treatment delay

VAP - conclusions VAP is associated with significant morbidity/mortality in ICU patients. The primary obstacle in diagnosing VAP is the absence of gold standard criteria, generating multiple implications for therapy Although a CPIS score > 6 may correlate with VAP, but the sensitivity, specificity are not encouraging The early appropriate antibiotics in adequate doses followed by de-escalation, is the major goal of VAP management