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Continuing Education Credit Date of Release: 6/15/2015 Date of Expiration: 6/14/2016 Estimated time to complete this educational activity: 1 hour Continuing Education Credit(s) • Physicians - This program has been reviewed and is acceptable for up to one (1.0) prescribed credit hour by the American Academy of Family Physicians. AAFP prescribed credit is accepted by the AMA as equivalent to AMA PRA Category I for the AMA Physicians‘ Recognition Award. When applying for the AMA PRA, prescribed hours earned must be reported as prescribed hours, not as Category I. • Nursing - Educational Review Systems is an approved provider of continuing education in nursing by ASNA, an accredited provider by the ANCC/Commission on Accreditation. Provider #5-115. This program is approved for one (1.0) hour. Educational Review Systems is also approved for nursing continuing education by the State of California and the District of Columbia. • Respiratory Therapy - This program has been approved for 1 contact hour Continuing Respiratory Care Education (CRCE) credit by the American Association for Respiratory Care, 9425 N. MacArthur Blvd.; Suite 100 Irving TX 75063. Course # 213078000. Laboratory Technicians - Educational Review Systems is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. Program. This program is approved for one (1.0) hour of continuing education credit. Statement of Need Ventilator-associated pneumonia (VAP) is a subtype of hospital-acquired pneumonia (HAP) which occurs in people receiving mechanical ventilation. Ventilator-associated pneumonia is difficult to diagnose and surveillance is curtailed by the subjectivity of many components of the surveillance definition. This learning activity will describe how bedside analyte testing may assist with therapeutic decision making and improve the prognosis for patients with VAP. Intended Audience The primary audience for this learning activity are health care professionals (physicians, nurses and respiratory therapists) involved in the testing, diagnosis, treatment, and management of ventilator-associated pneumonia and who are interested in the role of biomarkers to improve care for these patients. Learning Objectives After completing this activity, the participant should be able to: 1. Identify the risk factors of VAP. 2. Review the epidemiology of VAP. 3. Describe guidelines and recommendations used in the diagnosis and treatment of VAP. 4. Identify the benefits and limitations of point-of-care testing in VAP patients. Ventilator-Associated Pneumonia Ventilator-Associated Pneumonia • Ventilator-associated pneumonia (VAP) can develop in any patient on a ventilator.1 • VAP is the most common of the hospital-acquired infections (HAIs) in the intensive care unit (ICU).2 • The majority of VAP infections occur in patients who are intubated or mechanically ventilated for over 48 hours.2-3 – Ventilators are thought to be vectors for these infections. 1Centers for Disease Control. VAP FAQs. http://www.cdc.gov/HAI/vap/vap_faqs.html. Accessed April 6, 2014. SL, Kowalski CP, Damschroder L, et al. Infect Control Hosp Epidemiol. 2008;29:933-40. 3Tedja R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/ health-care-associated-pneumonia. Accessed April 6, 2014. 2Krein Pathogenesis • Hospitalized patients who are mechanically ventilated or heavily sedated are at highest risk. – Impaired immune defenses – Comorbidities – Immunosuppressant medications • Pathogens may depend on oropharynx colonization. – Micro- or bolus-aspiration 1Tedja R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectiousdisease/health-care-associated-pneumonia. Accessed April 6, 2014. Methods of Lung Contamination • • • • 1Tedja Inoculation during the intubation process Contaminated aerosol or ventilator condensate Endotracheal tube biofilm Aspiration – Gastric overgrowth – Infected sinus secretions – Pooled oropharyngeal secretions R, Gordon S. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectiousdisease/health-care-associated-pneumonia. Accessed April 6, 2014. Microbe Types • Monomicrobial versus polymicrobial • Bacteria – Gram negative bacteria are the most common type of bacteria seen in VAP. • Viruses • Fungi (rarely ever causative of VAP) 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/infectiousdisease/health-care-associated-pneumonia. Accessed April 6, 2014. Combes A, Figliolini C, Trouillet J et al. Chest. 2002;121(5):1618-23. Bacteria Associated With VAP Number of VAP Episodes 70 N = 124 Total number of episodes 60 Episodes with gram negative bacteria 50 Episodes with S. aureus and other cocci 40 30 20 10 0 1 2 3 Number of Bacterial Species Adapted from Combes A, Figliolini C, Trouillet J et al. Chest. 2002;121(5):1618-23. 4 Outcome Parameters for VAP Monomicrobial VAP (N = 65) Polymicrobial VAP (N = 59) Mortality at 30 d 23 (35) 15 (25) ICU mortality 35 (54) 27 (46) Duration of MV after VAP, d 21.0 ± 25.2 21.1 ± 24.0 MV-free days 30 d after VAP, d 9.0 ± 25.2 8.9 ± 24.0 ICU stay after VAP, d 25.3 ± 28.3 25.8 ± 23.4 Hospital stay after VAP, d 28.6 ± 28.7 30.8 ± 24.5 Appropriate initial antibiotics therapy† 60 (92) 44 (75) Patients who relapsed 12 (18) 16 (27) 21.9 ± 6.6 20.2 ± 9.9 Outcome Parameters Time to relapse, d Values given as mean ± SD or No (%). ICU, intensive care unit; MV, mechanical ventilation; VAP, ventilator associated pneumonia; d, day(s) † P < 0.01 Combes A, Figliolini C, Trouillet J et al. Chest. 2002;121(5):1618-23. Risk Factors VAP Risks Duration of intubation Male gender Trauma admission Severity of illness Prior use of antibiotics Prior use of histamine type 2 receptor antagonists Supine positioning Transport out of ICU Rello J, Ollendorf DA, Oster G et al. Chest. 2002;122(6):2115-21. VAP Increases Length of Stay and Ventilation Duration Type of Patient and Variable All patients Intubation duration* VAP onset ≤ 4 days VAP onset > 4 days Intensive care unit LOS VAP onset ≤ 4 days VAP onset > 4 days Hospital LOS VAP onset ≤ 4 days VAP onset > 4 days Survivors** Intubation duration Intensive care unit LOS Hospital LOS Median Number of Days (Range) Control Case Patients Patients (n = 30) (n = 90) P-Value 10.1(3–25) 9.1(3–20) 12.9(5–25) 18.5(5–33) 11.5(5–29) 23.5(6–33) 26.5(5–36) 18.5(5–31) 31.5(20–36) 4.7(1–22) < 0.001 8(2–33) < 0.001 14(3–50) < 0.001 10.2(3–25) 19(5–33) 29(12–36) 4.8(1–22) 8(2–33) 16(3–50) < 0.001 < 0.001 < 0.001 * Duration after VAP onset; ** There were 25 case patients and 61 control patients who survived. Restrepo M, Anzueto A, Arroliga A et al. Infect Control Hosp Epidemiol. 2010;31(5):509-15. 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 at between $5,000 and $20,000 per diagnosis.1 • Billed hospital charges are significantly greater for patients with VAP compared to patients without VAP.2 – $104,983 ± $91,080 versus $63,689 ± $75,030, respectively (P < 0.001). 1Koenig 2Rello SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. J, Ollendorf DA, Oster G et al. Chest. 2002;122(6):2115-21. Epidemiology Incidence • 250,000-300,000 estimated U.S. VAP cases per year1 • 5-10 cases per 1,000 hospital admissions • Increased in trauma centers versus general hospitals2 – 72.3% of trauma centers are above National Healthcare Safety Network (NHSN) benchmark for all hospitals. 72.3% 1Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. CP, Fakhry SM, Ferguson PL et al. J Trauma Acute Care Surg. 2012;72(5):1165-73. 2Michetti Mortality • Crude mortality rates for VAP are 10-40%.1 • VAP increases mortality of ventilated patients up to 46% VAP Mortality (%) • compared to ventilated patients without VAP (32%).2 Mortality rates are lower in long term acute care hospitals (~15%).3 1Cocanour 27-50% ~15% Long Term Acute Care CS, Peninger M, Domonoske BD et al. J Trauma. 2006;61:122-30. JA, Abed MS. Am J Infect Control. 2010;38:552-6. 3American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171:388-416. 2Al-Tawfiq Factors Associated With VAP Mortality Type of patient • Surgical • Trauma • Respiratory distress syndrome Organisms • Mono versus polymicrobial • Gram positive versus negative • P. aeruginosa, Acinetobacter spp., or S. maltophilia Hospital-specific diagnostic/treatment criteria Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. Guidelines and Recommendations Guidelines • In 2011 the CDC convened a Working Group for VAP and other ventilator-associated events (VAEs). • 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 CDC. Device Associated Module. 2014. Guidelines • Society for Healthcare Epidemiology of America/Infectious Diseases Society of America Section 1: Rationale and Statements of Concern Section 2: Strategies to Detect VAP Section 3: Strategies to Prevent VAP Section 4: Recommendations for Implementing Prevention and Monitoring Strategies Section 5: Performance Measures Coffin SE, Klompas K, Classen D, et al. Infect Control Hosp Epidemiol. 2008;S31-40. Recommendations: VAP Surveillance 1. Surveillance definition* a. The definition of VAP is perhaps the most subjective of the common device‐related healthcare‐associated infections. Most hospital epidemiologists and infection prevention and control professionals use the VAP definition put forth by the National Healthcare Safety Network, which uses 3 groups of criteria: clinical, radiographic, and microbiological. i. Despite the use of a common definition, significant interobserver variability has been noted. ii. Factors such as the surveillance strategy, diagnostic techniques, and microbiology and laboratory procedures likely account for some of the differences in VAP rates between different institutions. * The definition of VAP is currently ill defined. Most institutions develop their own guidelines to define the condition. Coffin SE, Klompas K, Classen D, et al. Infect Control Hosp Epidemiol. 2008;S31-40. Recommendations: VAP Surveillance 2. Methods for surveillance of VAP a. Active surveillance is required to accurately identify patients with VAP. Case finding by review of administrative data alone, such as discharge diagnosis codes, is inaccurate and lacks both sensitivity and specificity. i. Case finding of VAP is complex as a result of clinical criteria that vary with age and other host factors. ii. The need for review of 2 or more chest radiographs for patients with underlying pulmonary or cardiac disease also contributes to the difficulties. iii. Gram staining and semi-quantitative culture of endotracheal secretions or quantitative culture of specimens obtained through bronchoalveolar lavage should be performed for a patient suspected to have VAP. iv. Information technology can assist in the identification of patients with possible VAP, but cannot provide definitive identification and is not widely available. Coffin SE, Klompas K, Classen D, et al. Infect Control Hosp Epidemiol. 2008;S31-40. Recommendations: VAP Prevention General strategies that have been found to influence the risk of VAP a. General strategies i. Conduct active surveillance for VAP. ii. Adhere to hand‐hygiene guidelines published by the Centers for Disease Control and Prevention or the WHO. iii. Use noninvasive ventilation whenever possible. iv. Minimize the duration of ventilation. v. Perform daily assessments of readiness to wean and use weaning protocols. vi. Educate healthcare personnel who care for patients undergoing ventilation about VAP. Coffin SE, Klompas K, Classen D, et al. Infect Control Hosp Epidemiol. 2008;S31-40. Computer-Assisted Compliance • Computer-assisted compliance and automated surveillance technology are being used more frequently to control rates of VAP. • Hospitals using computer-assisted surveillance and compliance programs were more likely to provide: – Appropriate antibiotic therapy – Shorter time to appropriate therapy – Rapid de-escalation from β-lactams when unnecessary Halpin H, Shortell SM, Milstein A, Vanneman M. Am J Infect Control. 2011;39(4):270-6. Wilde AM, Nailor MD, Nicolau DP, Kuti JL. Pharmacotherapy. 2012;32:755–63. Diagnostics and Point-of-Care Diagnostic Methods Clinical Radiological Microbiological Diagnosing VAP requires a high clinical suspicion combined with bedside examination, radiographic examination, and microbiologic analysis of respiratory secretions. Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. Clinical Methods Accepted clinical criteria for pneumonia are of limited diagnostic value in definitively establishing the presence of VAP. Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. VAP Clinical Criteria Presence of a new or progressive radiographic infiltrate Plus at least two of three clinical features: Johanson Criteria - Fever > 38°C - Leukocytosis or leukopenia - Purulent secretions Rea-Neto A, Cherif M Youssef N, Tuche F et al. Critical Care. 2008;12:R56. VAP Clinical Criteria Temperature - 0 point: 36.5–38.4 °C - 1 point: 38.5–38.9 °C - 2 points: < 36 or > 39 Clinical Pulmonary °C Infection Score Blood leukocytes (CPIS) (cells/μL) - 0 point: 4000–11000 - 1 point: < 4000 or > 11000 - 2 points: > 500 band forms Oxygenation Tracheal secretions (PaO2/FiO2) (score) - 0 point: > 240 or ARDS - 0 point: < 14 - 2 points: < 240, - 1 point: > 14 no evidence of ARDS - 2 points: purulent sputum Pulmonary radiography Tracheal aspirate culture - 0 point: no infiltrate - 1 point: diffuse or patchy infiltrates - 0 point: minimal growth - 1 point: moderate or more growth - 2 points: localized infiltrate - 2 points: moderate or greater growth Score > 6 = VAP. ARDS = acute respiratory distress syndrome Rea-Neto A, Cherif M Youssef N, Tuche F et al. Critical Care. 2008;12:R56. Radiologic Methods • Portable chest radiograph is a component in the diagnosis of ventilated patients with pneumonia. – Problems with both sensitivity and specificity – Poor-quality films compromise the accuracy of X-rays. – Asymmetric pulmonary infiltrates consistent with VAP can be caused by noninfectious disorders. – Specificity of a pulmonary opacity consistent with pneumonia is only 27-35%. • Some radiograph findings can be useful when present. – Rapid cavitation of the pulmonary infiltrate – Air space process abutting a fissure (specificity, 96%) – Air bronchogram, especially if single (specificity, 96%) Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. Microbiological Methods Protected specimen brush Tracheobronchial secretion Bronchoalveolar lavage Positive Broncoscopic Methods Threshold (CFU/ml) Positive Cultures N = 60 VAPs BAL 104 56 (90%) TBS 105 56 (90%) PSB 103 50 (83%) TBS 106 30 (50%) Method BAL, bronchoalveolar lavage; CFU, colony-forming units; PSB, protected specimen brush; TBS, tracheobronchial secretion; VAP, ventilator-associated pneumonia. Woske H, Röding T, Schulz I, Lode H. Critical Care. 2001;5:167. Microbiological Method: Impact on Incidence • Incidence of VAP varies widely in the literature. • Clinical variability – – – – Different patient populations Different isolated pathogens Different types of ICUs involved Lack of consensus regarding microbiological diagnostic methods • Incidence – 5-9% using invasive methods (lower lung aspirates) – 41-67% based on clinical criteria (upper airway samples) Estellaa A, Álvarez-Lerma F. Med Intensiva. 2011;35:578-82. Qualitative versus Quantitative • Qualitative (Gram stain) – Advantages • Reproducible without special equipment – Disadvantages • Does not add to clinical diagnosis and often results in over• diagnosis Airways are colonized by pathogenic bacteria hours after intubation, regardless of presence of pneumonia • Quantitative – Advantages • Limits false positives and associated incorrect antibiotic use – Disadvantages • Results depend on equipment, location of sample, skill of operator Koenig SM, Truwit JD. Clin Microbiol Rev. 2006;19(4):637–57. Biomarkers • Microbiological techniques can take up to 48 hours1 • Previous use of antibiotics may give false-negatives1 • Identification of biomarkers may eliminate disadvantages of common VAP diagnostic techniques1-2 – Procalcitonin – sTREM-1 (not clinically available yet) – C-reactive protein • Current biomarkers have not been completely evaluated without prior antibiotic use.2 1Ramirez 2Palazzo P, Garcia MA, Ferrer M et al. Eur Respiratory J. 2008;31:356-62. SJ, Simpson T, Schnapp L. Heart Lung. 2011;40(4):293-8. 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 • Other tests limit the amount of time on the ventilator – Blood gasses 1Leone 2Rice M, Malavieille F, Papazian L et al. Critical Care. 2013;17:R170. LM, Reis AH, Mistry R et al. J Appl Microbiol. 2013;115:818-27. Thank You Please download the post-test or submit online to receive your continuing education credit. Date of Release: 6/15/2015 Date of Expiration: 6/14/2016 Estimated time to complete this educational activity: 1 hour