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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
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of Family Physicians. AAFP prescribed credit is accepted
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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