1. VENTILATOR ASSOCIATED PNEUMONIA
4/11/ :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.

2. 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

3. 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

4. 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

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

6. 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

7. VAP is common, morbid, and preventable.

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

9. 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

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

11. VAP - pathogenesis
exogenous
endogenous

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

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

19. 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

20. 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

21. 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

22. 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.

23. 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

24. 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

25. 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

26. VAP – positive airway cultures
Always VAP ?

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

28. 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

29. 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

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

31. 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

32. 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

33. 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

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

35. 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

36. 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

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

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

39. 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; September 2011; Chicago

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

41. 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

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

43. KPC “Tsunami”

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

50. VAP – antibiotic policy

51. VAP – treatment delay

52. 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