Managing VentilatorAssociated Tracheobronchitis VAT

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Managing Ventilator-Associated
Tracheobronchitis (VAT) Pneumonia
(VAP)Thinking Outside the Box

• Donald E. Craven, MD
• Chair, Infectious Diseases
• Lahey Clinic Medical Center
• Professor of Medicine
• Tufts University School of Medicine
• donald.e.craven_at_lahey.org

VAT/VAP NE Sinai 6-09
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CRAVEN DISCLOSURES

• Research Bard (NASCENT)
• Honoraria Merck, Pfizer, Ortho-McNeill,
• Covidien, Sanofi Pasteur,
• Bayer-Nektar, Wyeth, Arpida
• DSMB Johnson Johnson

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Agenda

• Pathogenesis VAT VAP
• VAT/VAP definitions overlap
• Targeted vs empiric therapy
• Prevention Its the tube

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Remember how much you dont know.
William Osler
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Which is the MOST IMPORTANTrisk factor for
developing VAP?

• Virulence of the bacteria?
• Number of bacteria/ml of sputum?
• Presence of a MDR pathogen?
• Presence of an endotracheal tube?

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VAP Facts

• ETT 6 to 21-fold gt risk
• gt 50 MICU antibiotics
• Mortality 20- 50
• Morbidity HUGE!
• Cost 15,000 - 40,000

Chastre, Am J Resp Crit Care Med 2002 165867-03
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PATHOGENESIS

• VAT vs VAP

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VAT VAP Pathogenesis
NP Colonization ETT Cuff Leaks ETT Biofilm
Colonization
N U M B E R S
Tracheal Colonization Bacteria vs Host Defenses
War Zone
Colonization VAT vs VAP (Q-ETA gt 106 cfu/ml)
Outcomes
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Lung One-Way In Out
ETT Cuff Biofilm
VAT
Bacteremia
VAP
Translocation
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Tracheal Ciliated Epithelium (Rabbit)
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Lung Tissue A Sponge
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Histology of Lung Tissue
Blood Vessels
Alveoli
Alveoli
http//microphotonics.com
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The Chase
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VAP Management Principles
1. VAP an infectious disease! 2. Every patient
has bacterial tracheal colonization 3.
Pathogen numbers important VAT/VAP ETA gt
106 cfu/m
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VAP Bacterial Pathogens

• Non- MDR
• Pneumococcus
• Haemophilus
• S. aureus - MSSA
• Legionella

• MDR
• P. aeruginosa
• Acinetobacter
• ESBL/KPC GNR
• MRSA

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Resistance vs Virulence
All bacteria are not created equal
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Bacterial Genes Virulence Vary Within the
Same Genus Species

• WHICH HAS GREATER SIMILARITY?
• E. coli K1 vs Toxigenic E. coli 0157
• (Hamburgers, Petting Zoos, Spinach)
• OR
• The Two Individuals in the Next Slide?

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Genetic Similarity of These Two 98
E. coli strains 50
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MRSA Virulence GenesHiramatsu, Lancet 2001

• MRSA/VISA/CA-MRSA genome sequenced
• 70 new virulence factors
• Possible targets for
• Diagnostics
• Therapy vaccines

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• VAP
• Hawthorne Effect?
• Prevention, Bundles?
• Manipulation?
• A Definition Problem?

Is VAP An Historic Disease?
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DefinitionsAre Critical

• VAT vs VAP

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vs.
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Quantitative Cultures for Diagnosis of UTIs,
IVCs Wounds

• Used to define urinary tract infections
• gt105 CFU/ml of a pathogen - voided urine
• gt104 CFU/ml - straight catheter urine
• IV catheter infections - gt15 cfu
• Wound infections - biopsy

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VAP A Bacterial Numbers Game!
Nasopharynx 108-1010 orgs/ml
VAT/VAP SQ-ETA, Q-ETA gt 106/cfu/ml
CASS
VAP BAL/PSBgt 104/cfu/ml
Cuff
B
Craven, Sem Resp Dis, 1996
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75-yo Man Admitted With Cardiac Arrest,
Intubated

• ETA
• Gram stain PMNs
• (many GNR)
• Cultures pending
• Portable CXR
• ? infiltrate

• PMH
• DM, COPD CHF
• Prior UTIs
• Day 8
• Temperature 100 F
• Purulent sputum
• WBC 11 k (75 polys)

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Diagnosis VAT or VAP?

• VAT Observe, NO antibiotics
• VAP Rx Empiric antibiotics
• VAT Rx Empiric antibiotics
• Dont know, dont care!

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When is an Infiltrate Pneumonia?
?LLL Pn vs atelectasis
CHF, ARDS r/o Pn
?RLL Pn
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VAP Reporting Cheating?
VAT VAP Fever, leukocytosis, Purulent
sputum, Bacterial pathogen, Q-ETA or SQ-ETA
VAP BAL gt 104 cfu/ml or New infiltrate CXR
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Which has the Greatest NEGATIVE Impact on VAP
Outcomes ?

• MDR bacteria
• Bacterial virulence toxins
• Inappropriate antibiotic therapy

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HOST Age, Underlying Disease, Devices
Appropriate Antibiotics
Battleground Pathogen Type vs. Defenses
HCAP, HAP VAT, VAP
Time
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Early, Appropriate Antibiotic TherapyReduces
Patient Mortality
Dupont H, et al. Intensive Care Med.
200127355-362 Ruiz M, et al. Am J Respir Crit
Care Med. 2000162119-125 Sanchez-Nieto JM, et
al. Am J Respir Crit Care Med. 1998157371-376
Kollef MH, et al. Chest. 1999115462-474
Alvarez-Lerma F, et al. Intensive Care Med.
199622387-394 Luna CM, et al. Chest.
1997111676-685.
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Empiric Therapy ATS/IDSA GUIDELINESAJRCCM
2005 171388
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ATS/IDSA Guidelines for VAP TherapyATS/IDSA, Am
Rev Resp Crit Care Med 2005 171 388

• Empiric early, appropriate adequate therapy
  based on MDR risk factors
• 2. De-escalate 48-72 hr based on clinical
  response culture results
• Limit duration 7 days

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Empiric Therapy for VAP ATS/IDSA Guidelines
AJRCCM 2005 171388
Stage 1
Risk Factors MDR Pathogens (Prior Antibiotics,
Hospitalization Chronic Care, Late Onset VAP)
No
Yes
Limited Spectrum Abx Ceftriaxone Azithromycin
or 3rd - 4th FQ or Ampicillin/Sulbactam /-
Azithromycin
Broader Spectrum Anti-Ps Abx 3rd - 4th
Cephalosporin or Carbapenem or BL/BLI FQ or
AG /- Vancomycin or Linezolid
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ARE WE WAITING TOO LONG TO INITIATE
THERAPY?Crude Diagnostics, Definitions,Increase
d Bacterial Numbers, More Inflammation, Tissue
Damage Complications?
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Empiric Therapy vs Targeted Therapy
Concepts
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Nasopharyngeal Colonization
Bacteria/Secretions ETT Cuff leaks, Biofilm
Bacterial Pathogens Number, Type
Virulence
Lung Defenses Cilia, Humoral, Cellular
Tracheobronchial Colonization
VAT
VAP
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Targeted vs Empiric
ATS/IDSA-VAP
VAT Model
VAP Suspected Broad Spectrum Antibiotics
Surveillance ETAs Pathogen ID/Sensitivity
Diagnosis VAT/VAP Q-ETA 106 cfu/ml
Empiric Therapy
Pathogen ETA/BAL ID Sensitivity 48-72 hr
Targeted Antibiotics
De-escalation
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VAT Epidemiologic Outcomes Data

• MICU/SICU patients MVP gt 48 hrs
• Incidence of VAT ranges from 3-11
• Pathogens P. aeruginosa, Acinetobacter, MRSA
• VAT gt LOS in ICU MV days, mortality
• Antibiotic Rx lower mortality, MICUs pts
  (plt.04)

Nseir, Eur Respir J 2002 20 1483-89
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The VAT ModelThinking Outside the Box

• VAT/VAP a numbers game
• Clinical signs, symptoms overlap
• Microbiology Q-ETA gt 106 cfu/ml diagnostic
• Chest x-ray negative early, NOT
  specific
• Surveillance Q-ETA for early diagnosis
• Targeted therapy better
• Preventing VAP improves outcomes

Nseir Crit Care 2008, Craven, Chest 2009
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VAT
gt106
Targeted
P. aeruginosa
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VAT A Better Clinical Focus?

• Surveillance serial Q-ETAs for pathogens
• RCT of VAT Q-ETA 106 cfu/mL, CXR normal
• Targeted antibiotics for VAT vs no therapy
• Reduced VAP rate (14 vs 47, p.01)
• Reduced ICU mortality (plt.05)
• More MV-free days (plt.001)
• Pathogens P. aeruginosa MRSA

Nseir S et al, Crit Care 200812R62
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VAT A Model to Prevent VAP
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VAT Model Advantages

• Standardized microbiologic diagnosis
• Surveillance ETA to identify MDR pathogens
• Targeted beats empiric therapy
• Earlier, appropriate therapy
• Should not alter most prevention strategies
• Better for public reporting
• Model for clinical therapy prevention trials

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VAT Model Issues

• Need more data studies
• Q-ETA vs SQ-ETA criteria for VAT Dx?
• Duration of VAT therapy unknown?
• Incidence data needed impact on VAP?
• Frequency of surveillance cultures used?
• Pathogen(s) constant or changing?
• Topical antibiotics may alter Q-ETA?
• Not yet a standard of care?

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Summary

• VAT VAP diagnoses overlap
• VAT model allows
• standardized microbiologic diagnosis
• earlier targeted antibiotic therapy
• improved outcomes VAP prevention
• More data clinical VAT trials are needed

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PreventionTrumpsDiseaseIts the Tube.!
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Semmelweis
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Success Reducing Mistakes Doing Little
Things 8 Days a Week

• Infection Control
• Decrease Devices Days
• Antibiotic Control
• Team Work Education

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VAP Bundle All or None
100,000 Lives Campaign VAP Bundlewww.IHI.org

• Head of bed 30-45o
• Sedation (type) vacation (weaning)
• 3. Stress bleeding
• prophylaxis (H2/SUC)
• 4. DVT prophylaxis

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• Sedation Weaning Protocol
• SATs spontaneous awakening trials
• SBTs spontaneous breathing trials
• Awakening Breathing Control (ABC)
• group (n 168) vs controls (n 167)

Girard, Lancet 2008 371126-34
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Sedation Weaning Protocol

• ABC group (n 168) vs controls (n 167)
• More days spontaneous breathing (plt.02)
• Discharged earlier from ICU/hospital (plt .01)
• Reintubations similar, reduced tracheostomy
• Increased survival overall (plt.01)
• Should be routine practice in ICUs

Girard, Lancet 2008 371126-34
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Sedation Weaning Protocol Girard, Lancet 2008
371126-34
plt.02
plt.01
Extubated
ICU Discharge
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1-Year Survival Rates
- 32, plt.01
Girard, Lancet 2008 371126-34
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Non-Invasive Ventilation (NIV)
Courtesy of Massimo Antonelli, MD, Rome, Italy
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NIV vs MVP Outcomes

• Variable NIV MVP
  p
• NI 18 60
  .001
• NP 8 22
  .04
• ABx Rx 8 26
  .01
• Vent days 6 12
  .01
• LOS 9 15
  .02
• Mortality 4 26
  .002

Girou JAMA 2000 2842361-67
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• CASS tube, with evacuation port, provides
  continuous suctioning of subglottic secretions
  bacteria.
• A large, elliptical evacuation port is located
  proximal to the cuff.

Subglottic space
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CASS Tubes New Modifications

• Endotracheal tubes with dorsal lumen for
  subglottic secretion drainage.
• The dorsal lumen opens above the endotracheal
  cuff.
• In the current version, this hole is closer to
  the cuff and the lumen is larger.

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CASS Prevents VAP
CASS Control
Mahul 9/70 (13)
21/75 (28) Valles 16/95 (17)
25/95 (26) Kollef
8/160 ( 5) 15/183 (
8) Bo 8/35 (23)
15/33 (45) Smulders 3/75 ( 4)
12/74 (16) Lorente 11/140
( 8) 31/140 (22) Bouza
12/359 ( 4) 19/331
( 5) Bouza gt48h 12/45 (27)
19/40 (48) p lt 0.05
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CASS for Prevention of VAP Meta-analysis
VAP
Mortality
Early VAP
Dezfulian, Am J Med. 200511811-18.
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(CASS) for Prevention of VAP Meta-analysis
MVD LOS
Dezfulian C, et al. Am J Med. 200511811-18.
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Cuff Technology

• Current cuffs are not 100 occlusive against
  fluid leakage, regardless of inflation pressure
• When properly sized cuffs are appropriately
  inflated, folds in wall create channels leakage
• Folding is related to cuff shape and material

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Microchannels in an Inflated Cuff
Dullenkopf ICM 2003291849
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New Cuff Technology

• Thinner cuff material and/or unique shape reduce
  leakage

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• CASS

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ETT Biofilm A Bacterial Insurance Policy Prince
AS NEJM 2002 3471110-1111

• Antibiotic Issues
• Decreased penetration
• Lower concentration
• Reduced bacterial killing
• Impaired Host immunity
• Ab complement
• PMNs Mø
• Bacteria persistence
• Distal emboli
• REMOVE DEVICES!!

Cell Phones Quorum Sensing
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The North American Silver-Coated Endotracheal
Tube (NASCENT) Study A Randomized, Contolled
Trial
Silver Endotracheal Tube
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The NASCENT Study ResultsMicrobiologically-confir
med VAP
36 (p0.03)
Microbiologically confirmed VAP Rate
Kollef, JAMA 2008 300 805-813
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The NASCENT Study Results
Kollef, JAMA 2008 300 805-813
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NASCENT Study

• No difference in MVD days
• No difference in ICU stay
• No difference in mortality

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Summary Prevention Trumps All!

• Teamwork, staffing education,
• Bundles, removing devices, oral care
• Infection antibiotic controls
• CASS, silver-coated tubes effective
• Targeting VAT to prevent VAP

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Need for a Well Conducted TEAMStrategies, Goals
Support
BSO, HROs Hospitals
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Remember how much you dont know and dont
apply
William Osler
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The pure and simple truthis rarely pure and
never simple.

• Dylan Thomas
• 1914-1953

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Make It Happen!
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Thanks for Your Attention
Questions