Transcript 14-L-HAI-SPICE-Part 1-HAP-VAP-April 2014

HEALTHCARE-ASSOCIATED
PNEUMONIA: EPIDEMIOLOGY,
PATHOGENESIS & PREVENTION 2014
David Jay Weber, M.D., M.P.H.
Professor of Medicine, Pediatrics, & Epidemiology
Associate Chief Medical Officer, UNC Health Care
Medical Director, Hospital Epidemiology
University of North Carolina at Chapel Hill
HAZARDS IN THE ICU
Weinstein RA. Am J Med 1991;91(suppl 3B):180S
TOPICS: HCAP, HAP, VAP
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Epidemiology
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Pathogenesis
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Impact of healthcare-associated infections
Definitions
NHSN surveillance definitions
Incidence and prevalence of HCAP, HAP, VAP
Mechanisms of pneumonia
Microbiology
Risk factors
Diagnosis
Prevention
GOALS OF LECTURE
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Understand the epidemiology of nosocomial pneumonia
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Understand the pathophysiology of HAP & VAP
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Impact
Incidence
Risk factors for acquisition and mortality
Microbiology
Diagnosis
Treatment
Understand methods of prevention
Marrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-S362
Chroneou A, et al. Expert Opinion 2007;8:3117-31
HEALTHCARE-ASSOCIATED
PNEUMONIA
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HAI
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An infection is considered an HAI if ALL elements of a CDC/NHSN sitespecific criterion were first present together on or after the 3rd hospital
day (day of admission is Day 1). For an HAI, an element of the
infection criterion must be present during the first 2 hospital days as
long as it is also present on or after Day 3. All elements used to meet
the infection criterion must occur within a timeframe that does not
exceed a gap of 1 calendar day between elements
Pneumonia (PNEU)

Pneumonia is identified using a combination of radiologic, clinical and
laboratory criteria. For VAP the date of the event is the date when the
last element used to meet the pneumonia criteria are occurred.
http://www.cdc.gov/nhsn/acute-care-hospital/vae/index.html
VENTILATOR-ASSOCIATED EVENT
(adult patients >18 years of age
VENTILATOR-ASSOCIATED EVENTS
(VAE) SURVEILLANCE ALGORITHM
VENTILATOR-ASSOCIATED
CONDITION (VAC)
INFECTION-RELATED VENTILATORASSOCIATED COMPLICATIONS (IVAC)
POSSIBLE VENTILATOR-ASSOCIATED
PNEUMONIA (VAP)
PROBABLE VENTILATOR-ASSOCIATED
PNEUMONIA (VAP)
THRESHOLD VALUES FOR CULTURED SPECIMENS
USED IN THE PROBABLE VAP DEFINITION
NHSN DEFINITIONS OF HAP AND VAP
(children, <18 years of age)
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Table 1. Specific site algorithms for clinically defined pneumonia
(PNU1)
Table 2. Specific site algorithms for pneumonia with common
bacterial or filamentous fungal pathogens and specific laboratory
findings (PNU2)
Table 3. Specific site algorithms for viral, Legionella, and other
bacterial pneumonias with definitive laboratory findings (PNU2)
Table 4. Specific site algorithm for pneumonia in
immunocompromised patients (PNU3)
Marrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-S362
PNU1
PNU2
PNU2
PNU3
HAP & VAP: IMPACT
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Potential complications of mechanical ventilation
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Complications result in longer ICU stays, increased costs, and
increased risk of disability and death
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Pneumonia, acute respiratory distress syndrome (ARDS), pulmonary
embolism, barotrauma, pulmonary edema, and death
Mortalioty in patient with acute lung injury, estimated to range from 24% in
patients 15-19 years of age to 60% for patients >85 years of age
Prevalence: 2010 NHSN = 3,525 cases of VAP
Incidence: 2010 NHSN = 0.0-5.8 per 1,000 ventilator days
Magill SS, et al. New Engl J Med 2014;370:1198
HAP: IMPACT
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Accounts for ~15% of all healthcare-associated infections
(3rd most common cause of HAIs after UTIs and SSIs)
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Accounts for ~25% of all nococomial infections in the ICU (50%
of antibiotics provided)
Number of cases per year: ~275,000
 Prevalence
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VAP develops in 10% to 20% of mechanically ventilated
patients
VAP rate = 1-4 cases/1,000 ventilator-days
HAP: IMPACT
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Cost
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Mortality
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Increases hospital stay by an average of 7-11 days
Cost per patient >$40,000
Direct cost (estimated) of excess hospital stays = $1.5 billion/year
Crude mortality: 30-70% (average 40%)
Attributable mortality: 33-50%
Deaths
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Deaths directly caused by infection: 7,085 (3.1%)
Deaths to which infection contributed: 22,983 (10.1%)
PREVALENCE: ICU (EUROPE)
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Study design: Point prevalence rate
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17 countries, 1447 ICUs, 10,038 patients
Frequency of infections: 4,501 (44.8%)
Community-acquired: 1,876 (13.7%)
 Hospital-acquired: 975 (9.7%)
 ICU-acquired: 2,064 (20.6%)
 Pneumonia: 967 (46.9%)
 Other lower respiratory tract: 368 (17.8%)
 Urinary tract: 363 (17.6%)
 Bloodstream: 247 (12.0%)
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Vincent J-L, et al. JAMA 1995;274:639
PREVALENCE: ICU (WORLDWIDE)
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Study design: Point prevalence, 8 May 2007
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Frequency of infections: 7,087 (51%)
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75 countries, 1265 ICUs, 13,796 adult patients
Sites of infection
 Respiratory tract:: 4,503 (63.5%)
 Abdominal: 1,392 (19.6%)
 Bloodstream: 1,071 (15.1%)
 Renal/urinary tract: 1,011 (14.3%)
Antibiotic therapy: 71%
Pathogens of infected patients: 47% GPC, 62% GNR, 19% fungi
Infected patients had higher ICU (25.3% vs 10.7%) and hospital
mortality (33.1% vs 14.8%)
Vincent J-L, et al. JAMA 2009;302:2333-2329
VENTILATOR-ASSOCIATED PNEU RATES,
NHSN, 2012
VENTILATOR-ASSOCIATED PNEU RATES,
NHSN, 2012
VAP: TIME COURSE
Cumulative Incidence ICU VAP
60%
Garrard C. Chest 1995;108:17S
50%
40%
30%
20%
10%
0%
5
10
15
Days
20
25
30
VAP: TIME COURSE
Mean Daily Risk Of VAP
5.0%
4.0%
3.0%
2.0%
1.0%
0.0%
0-5
6-136
11-15
16-20
Days
21-25
26-30
TOP 7 PATHOGENS ASSOCIATED WITH
VAP: NHSN, 200
S. aureus
P. aeruginosa
Klebsiella pneumoniae/oxytoca
Enterobacter spp.
Acinetobacter
E. coli
Sievert DM. ICHE 2013; 34;1-14
Serratia spp.
Other
0%
5%
10%
15%
20%
25%
30%
ETIOLOGIC AGENTS ASSOCIATED WITH HAP: NNIS vs INVASIVE DX
Pathogen
S. aureus (ORSA 55.7%)
S. Pneumoniae
Streptococcus spp.
Coagulase-negative staphylococcus
Enterobacteriaceae
Pseudomonas aeroginosa
Acinetobacter spp.
Stenotrophomonas maltophilia
Hemophilus spp.
Neisseria spp.
Anaerobes
Fungi
Other (<1% each)
NNIS
19%
NA
3%
2%
26%
17%
4%
<1%
7.1%
<1%
2%
7%
INVASIVE DX
20.4%
4.1%
8.0%
1.4%
14.15
24.4%
7.9%
1.7%
9.8%
2.6%
0.9%
0.9%
3.8%
Chastre J, Fagon J-Y. Am J Respir Crit Care Med 2002;165:867-903
MICROBIOLOGY
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Determinants of pathogens
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Setting
Prior antibiotic use
Duration of hospitalization
 Early (<5 days): S. pneumoniae, H. influenzae, MSSA
 Late (>5 days): P. aeruginosa, MRSA, Gram (-) bacilli
ICU stay
Colonization
COMMON PATHOGENS BY PRESENCE OR
ABSENCE OF RISK FACTORS FOR MDROs
Vincent JL, et al. Drugs 2010;70:1927-1944
Weber DJ, et al. ICHE 2007;28:825-831
ICU (NNIS, 1989-99): Ventilator-Associated Pneumonia
Open bars <7 days hospitalization
Closed bars >7 days hospitalization
Fridkin SK. Crit Care Med 2001;29:N67
PATHOGENS AS A FUNCTION OF
DURATION OF HOSPITALIZATION
Weber DJ, et al. ICHE 2007;28:825-831
Antibiotic-Resistant VAP
P aeruginosa
Acinetobacter baumannii
MRSA
Variable
Prior MV
>7 days
Prior ABs
Broad ABs
Odds
Ratio
6
13
4
P Value
0.009
<0.001
0.025
Organism (%)
25
20
15
10
5
0
–/–
MV = Mechanical ventilation.
MRSA = Methicillin-resistant S
aureus.
–/+
+/–
+/+
MV>7 Days/Prior Antibiotics
Trouillet JL, et al. Am J Respir Crit Care Med. 1998;157:531-539.
PATHOGENESIS
Colonization, aspiration, pneumonia in the setting of
impaired host defenses
 Inhalation
 Instillation
 Bacteremic spread
 Contiguous spread
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Kollef MH, et al. Chest 2004;32:1396
VAP: RISK FACTORS
Intrinsic Risk Factors
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Extrinsic Risk Factors
Chronic lung disease/COPD
Severity of illness
ARDS
Witnessed aspiration
Age >60 years
Coma
Head trauma/ICP monitoring
Upper abdominal surgery
Thoracic surgery
Fall-winter season
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Duration of intubation
Emergent intubation
Reintubation
Elevated gastric pH
Prior antibiotic therapy
Nasogastric tube
Enteral nutrition
Supine head position
Patient transport out of ICU
Kollef M. Crit Care Med 2004;32:1396 (adapted)
%Hospital Mortality by Classification
P < 0.001
30
P < 0.0001
25
P > 0.05
20
15
10
5
0
10.0
CAP
HCAP
29.3
18.8
19.8
HAP
VAP
Kollef MH, et al. Chest 2005;128:3854
METHODS OF DIAGNOSIS
Clinical findings (symptoms, signs)
 Blood, pleural fluid analysis & cultures, tissue diagnosis
 Non-bronchoscopic
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Endotracheal aspiration
 Percutaneous needle aspiration
 Blind bronchial sampling (“Blind” BAL)
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Bronchoscopic techniques
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Protected specimen brush (PSB)
Bronchoalveolar lavage (BAL)
CLINICAL DIAGNOSIS
Symptoms and signs: Fever, respiratory distress
 Chest radiography: Infiltrate, consolidation, cavity
 Laboratory: Leukocytosis, leukopenia
 Sputum: Purulence (WBC), culture
 Clinical diagnosis (ATS/IDSA)
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New or progressive infiltrate
>2 of the following: Temperature >38 oC, leukocytosis or
leukopenia, purulent secretions
DIFFERENTIAL DIAGNOSIS:
FEVER AND PULMONARY INFILTRATES
Pulmonary infection
 Pulmonary embolism
 Pulmonary drug reaction
 Pulmonary hemorrhage
 Chemical aspiration
 Sepsis with acute respiratory distress syndrome
 Drug reaction

DIAGNOSING VAP PNEUMONIA
DIAGNOSING NOSOCOMIAL PNEUMONIA (Meduri G, et al. Chest 1994;106:221)
50
patients completed
the study
45
patients with a
definitive source
of fever identified
37
infectious
8
noninfectious only
19
pneumonia
14
sinusitis
catheter infection
urinary tract infection
candidemia
cholecystitis
empyema
peritonitis
6
pulmonary
2
extra-pulmonary
14
concomitant
infections
11
concomitant
infections
0
concomitant
infections
5 fibroproliferation
1 chemical aspiration
1 pancreatitis
1 drug fever
INDICATIONS FOR INVASIVE DIAGNOSIS
Routine for all patients with possible nosocomial
pneumonia?
 Targeted use of invasive diagnosis

Critically ill
 Immunocompromised patient (esp. T-cell defect)
 Deterioration on empiric therapy
 Failure to respond to empiric therapy
 Other therapeutic consideration (e.g., foreign-body)

PROTECTED SPECIMEN BRUSH
BRONCHOALVEOLAR LAVAGE
Meta-analysis of Invasive Strategies for the Diagnosis of
Ventilator-Associated Pneumonia & their Impact on Mortality*
Odds Ratio
(95% CI)
% Weight
Sanchez-Nieto, et al.
Ruiz, et al.
Fagon, et al.
Violan, et al.
2.42 (0.75,7.84)
0.71 (0.28,1.77)
0.71 (0.47,1.06)
1.08 (0.39,2.98)
13.0
19.5
50.9
16.5
Overall (95% CI)
0.89 (0.56,1.41)
Study
Favors Invasive Favors Non-Invasive
Approach
Approach
0.13
1
7.84
Odds Ratio for Mortality
*Random effects model; Test of heterogeneity p=0.247, for Odds ratio p=0.620
Shorr A, Kollef. MH Crit Care Med 2005;33:46.
Morrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-352
EMPIRIC THERAPY: GENERAL RULES
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Know the flora and susceptibilities of the pathogens causing
nosocomial pneumonia at your own institution
Obtain history of antibiotic-allergies from all patients (adjust
regimen appropriately)
Choose empiric therapy to minimize drug interactions
Dose adjust (when appropriate) in patients with renal and/or
hepatic failure
Consider specific contraindications or precautions (e.g.,
pregnancy, neuromuscular disease)
All other things being equal use the least expensive therapy
Provide appropriate non-antibiotic care
IMPACT OF ANTIMICROBIALS
60
Inadequate Therapy n = 169
Adequate Therapy n = 486
50
40
Hospital
Mortality 30
%
20
10
0
Kollef Chest 115:462, 1999
All Cause
Infection-related
HAP: The Importance of Initial Empiric
Antibiotic Selection
Adequate init. antibiotic
100
Inadequate init. antibiotic
91
% mortality
80
63
61.4
60.7
60
50
41.5
40
43
38
0
39
33.3
24.7
20
47.3
25
16.2
P=NS
AlvarezLerma
P=0.06
Rello
P<0.001
P=0.001
Luna
Kollef
P=NS
SanchezNieto
P=NS
Ruiz
Alvarez-Lerma F. Intensive Care Med 1996 May;22(5):387-394.
Rello J, Gallego M, Mariscal D, et al. Am J Respir Crit Care Med 1997 Jul;156(1):196-200.
Luna CM, Vujacich P, Niederman MS, et al. Chest 1997;111(3):676-685.
Kollef MH and Ward S. Chest 1998 Feb;113(2):412-20.
Sanchez-Nieto JM, Torres A, Garcia-Cordoba F, et al. Am J Respir Crit Care Med. 1998;157:371-376.
Ruiz M, Torres A, Eqig, S, et al. Am J Respir Crit Care Med. 2000;162:119-125.
Dupont H, Mentec H, Sollet, JP, et al. Intensive Care Med. 2001;27(2):355-362
P=NS
Dupont
61
ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416
ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416
Vincent J-L, et al. Drugs 2010;70:1927-1944
ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416
DURATION OF THERAPY: STUDY DESIGN
Authors: Chastre J, et al. JAMA 2003;290:2988
 Study goal: Compare 8 vs 15 days of therapy for VAP
 Design: Prospective, randomized, double-blind (until day
8), clinical trial
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VAP diagnosed by quantitative cultures obtained by bronchoscopy
Location: 51 French ICUs (N=401 patients)
 Outcomes: Assessed 28 days after VAP onset (ITT
analysis)
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Primary measures = death from any cause
Microbiologically documented pulmonry infection recurrence
Antibiotic free days
DURATION OF THERAPY: RESULTS
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Primary outcomes (8 vs 15 days)
Similar mortality, 18.8% vs 17.2%
Similar rate of recurrent infection, 28.9% vs 26.0%
 MRSA, 33.3% vs 42.9%
 Nonfermenting GNR, 40.6% vs 25.4% (p<0.05)
 More antibiotic free days, 13.1% vs 8.7% (p<0.001)
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Secondary outcomes (8 vs 15 days)
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Similar mechanical ventilation-free days, 8.7 vs 9.1
Similar number of organ failure-free days, 7.5 vs 8.0
Similar length of ICU stay, 30.0 vs 27.5
Similar frequency death at day 60, 25.4% vs 27.9%
Multi-resistant pathogen (recurrent infection), 42% v 62% (p=0.04)
THERAPY: SUMMARY I
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Negative lower respiratory tract cultures can be used to stop antibiotic
therapy if obtained in the absence of an antibiotic change in past 72
hours
Early, appropriate, broad spectrum therapy, antibiotic therapy should
be prescribed with adequate doses to optimize antimicrobial efficacy
An empiric therapy regimen should include agents that are from a
different antibiotic class than the patient is currently receiving
De-escalation of antibiotic should be considered once data are
available on the results of the patient’s cultures and clinical response
A shorter duration of therapy (7-8 days) is recommended for patients
with uncomplicated HAP, VAP, or HCAP who have had a good clinical
response
THERAPY: SUMMARY III
 High
risk patients
 Multiple-drug regimens required
 Combine beta-lactam with aminoglycoside (preferred)
or quinolone (levo or cipro)
 Consider need for coverage of oxacillin-resistant
aureus, Legionella
S.
THERAPY: SUMMARY IV
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Bronchoscopy directed therapy
 May improve outcome
Demonstrated by a randomized study
 Several cohort studies have failed to demonstrated benefit

Mortality reduced by initial use of appropriate antibiotics
 Duration of therapy, in general, should be 7-8 days
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Kollef M. Chest 2004;32:1396
Morrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-352
Morrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-352
STRENGTH OF RECOMMENDATIONS
AND QUALITY OF EVIDENCE
STRATEGIES TO PREVENT VAP
IN ACUTE CARE HOSPITALS
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Surveillance
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Definition of VAP most subjective of all device associated HAIs
Significant intra-observer variability exists
Use active surveillance (not administrative data alone)
Ideally perform semiquantitative culture of endotracheal
secretions or quantitative culture of BAL fluid
Prevention
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Follow CDC guidelines to prevent VAP
Interrupt most common mechanisms by which VAP develops
 Aspiration of secretions
 Colonization of the aerodigestive tract
 Use of contaminated equipment
Coffin SE, et al. ICHE 2008;29 (suppl 1):S31-S40
STRATEGIES TO PREVENT VAP
IN ACUTE CARE HOSPITALS
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Prevention: General strategies
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Conduct active surveillance
Adhere to hand hygiene recommendations
Use non-invasive ventilation whenever possible
Minimize the duration of ventilation
Perform daily assessments of readiness to wean
Educate personnel regarding prevention
Prevention: Strategies to prevent aspiration
Maintain patients in a semirecumbent position (30o-45o
elevation)
 Use a cuffed ET tube with in-line or subglottic suctioning
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Coffin SE, et al. ICHE 2008;29 (suppl 1):S31-S40
STRATEGIES TO PREVENT VAP
IN ACUTE CARE HOSPITALS
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Prevention: Strategies to reduce colonization
Orotracheal intubation preferred to nasotracheal intubation
 Avoid acid suppressive therapy
 Perform oral care with an antiseptic solution
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Prevention: Strategies to minimize contamination
Use sterile water to rinse reusable respiratory equipment
 Remove condensate from the ventilatory circuit
 Change the ventilatory circuit only when visibly soiled or
malfunctioning
 Store and disinfect respiratory equipment properly
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Coffin SE, et al. ICHE 2008;29 (suppl 1):S31-S40
STRATEGIES TO PREVENT VAP
IN ACUTE CARE HOSPITALS
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Special approached for the prevention of VAP
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Use an ET tube with in-line and subglottic suctioning
Approaches that should not be routinely used
Do not routinely administer IVIG, GM-CSF, or chest physiotherapy
 Do not routinely use rotational therapy with kinetic or continuous
lateral rotational therapy beds
 Do not routinely administer prophylactic aerosolized or systemic
antimicrobials
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Unresolved issues
Selective digestive tract decontamination
 Avoidance of H2 antagonists or proton pump inhibitors
 Use of antiseptic-impregnated ET tubes
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Coffin SE, et al. ICHE 2008;29 (suppl 1):S31-S40
IHI GUIDELINE: VAP BUNDLE
Elevation of the head of the bed to between 30 and 45
degrees
 Daily “sedation vacation” and daily assessment of
readiness to extubate
 Peptic ulcer disease (PUD) prophylaxis
 Deep venous thrombosis (DVT) prophylaxis (unless
contraindicated)
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CONCLUSIONS I
Nosocomial pneumonia remains an important cause of
patient morbidity and mortality in the US
 Nosocomial pneumonia results in a more prolonged
hospital stay and increased cost
 Local epidemiology of pathogens and antibiograms are
critical to empiric and directed chemotherapy
 Determining the etiologic agent(s) of nosocomial
pneumonia is problematic even with new invasive
diagnostic techniques

CONCLUSIONS II
Use of empiric, broad-spectrum regimens remain critical
to favorable patient outcomes
 Single-drug regimens may be appropriate for some lowrisk patients, but two-drug regimens with broad spectrum
(including P. aeruginosa) are necessary for high-risk
patients
 Prevention is superior to treatment
