Transcript Nosocomial Pneumonia Eliane Haron,M.D. Nosocomial Pneumonia Epidemiology      Common hospital-acquired infection Occurs at a rate of approximately 5-10 cases per 1000 hospital admissions Incidence increases by 6-20

Nosocomial Pneumonia
Eliane Haron,M.D.
Nosocomial Pneumonia
Epidemiology
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Common hospital-acquired infection
Occurs at a rate of approximately 5-10 cases per 1000
hospital admissions
Incidence increases by 6-20 fold in patients being ventilated
mechanically.
One study suggested that the risk for developing VAP
increases 1% per day
Another study suggested, highest risk occur in the first 5
days after intubation
Nosocomial Pneumonia
Nosocomial Pneumonia
Epidemiology
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Nosocomial pneumonia is the leading cause of
death due to hospital acquired infections
Associated with substantial morbidity
Has an associated crude mortality of 30-50%
Hospital stay increases by 7-9 days per patient
Estimated cost > 1 billion dollars/year
Mortality and Time of Presentation of HAP
P<.001
P<.001
Hospital Mortality (%)
50
P = .504
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40
30
20
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10
0
*Upper 95% confidence interval
None
Early Onset
Late Onset
Nosocomial Pneumonia
Ibrahim, et al. Chest. 2000;117:1434-1442.
Nosocomial Pneumonia
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Hence, the importance of focusing on:
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Accurate diagnosis
Appropriate treatment
Preventive measures
Nosocomial Pneumonia
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Pathogenesis
Risk factors
Etiologic agents
Differential diagnosis
Treatment
Prevention
Nosocomial Pneumonia
Pathogenesis
Nosocomial Pneumonia
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Microaspiration may occur in up to 45% of healthy
volunteers during sleep
Oropharynx of hospitalized patients is colonized
with GNR in 35-75% of patients depending on the
severity and type of underlying illness
Multiple factors are associated with higher risk of
colonization with pathogenic bacteria and higher
risk of aspiration
Nosocomial Pneumonia
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Pathogenesis
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Invasion of the lower respiratory tract by:
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Aspiration of oropharyngeal/GI organisms
Inhalation of aerosols containing bacteria
Hematogenous spread
Colonization
Aspiration
MRSA*
HAP
Nosocomial Pneumonia
Risk Factors
Nosocomial Pneumonia
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Risk Factors
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Host Factors
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Extremes of age, severe acute or chronic illnesses,
immunosupression, coma, alcoholism, malnutrition,
COPD, DM
Factors that enhance colonization of the
oropharynx and stomach by pathogenic
microorganisms
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admission to an ICU, administration of antibiotics,
chronic lung disease, endotracheal intubation, etc.
Nosocomial Pneumonia
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Risk Factors
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Conditions favoring aspiration or reflux
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Mechanical ventilation
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Supine position, depressed consciousness, endotracheal
intubation, insertion of nasogastric tube
Impaired mucociliary function, injury of mucosa favoring
bacterial binding, pooling of secretions in the subglottic
area, potential exposure to contaminated respiratory
equipment and contact with contaminated or colonized
hands of HCWs
Factors that impede adequate pulmonary toilet
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Surgical procedures that involve the head and neck,
being immobilized as a result of trauma or illness,
sedation etc.
Nosocomial Pneumonia
Etiologic Agents
Nosocomial Pneumonia
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Etiologic Agents
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S.aureus
Enterobacteriaceae
P.aeruginosa
Acinetobacter sp.
Polymicrobial
Anaerobic bacteria
Legionella sp.
Aspergillus sp.
Viral
Pathogens Associated With HAP
P = .003
Early-onset NP
Nosocomial Pneumonia (%)
40
Late-onset NP
35
PA =
P aeruginosa
OSSA = Oxacillin-sensitive
S aureus
ORSA = Oxacillin-resistant
S aureus
ES =
Enterobacter
species
SM =
S marcescens
30
P = .408
25
P = .043
20
15
P = .985
P = .144
ES
SM
10
5
0
PA
OSSA
ORSA
Pathogen
Ibrahim, et al. Chest. 2000;117:1434-1442.
Nosocomial Pneumonia
Diagnosis
Nosocomial Pneumonia
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Diagnosis
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Not necessarily easy to accurately diagnose HAP
Criteria frequently include:
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Clinical
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Radiographic
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new or progressive infiltrates on CXR,
Laboratorial
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fever ; cough with purulent sputum,
leukocytosis or leukopenia
Microbiologic
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Suggestive gram stain and positive cultures of sputum,
tracheal aspirate, BAL, bronchial brushing, pleural fluid or
blood
Quantitative cultures
Nosocomial Pneumonia
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Problems
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All above criteria fairly sensitive, but very nonspecific, particularly in mechanically ventilated
patients
Other criteria/problems include
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Positive cultures of blood and pleural fluid plus clinical
findings (specific but poor sensitivity)
Rapid cavitation of pulmonary infiltrate absent Tb or
cancer (rare)
Histopathologic examination of lung tissue (invasive)
Nosocomial pneumonia
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Bronchoscopically Directed Techniques for diagnosis
of VAP and Quantitative cultures
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Bronchoscopy with BAL/bronchial brushings (10,000 to
100,000 CFU/ml and less than 1% of squamous cells)
Protected specimen brush method (>10³ CFU/ml)
Protected BAL with a balloon tipped catheter (>5% of
neutrophils or macrophages with intracellular organisms on
a Wright-Giemsa stain)
Nosocomial pneumonia
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Multiple studies looked into the accuracy of quantitative culture and microscopic
examination of LRT secretions as compared to histopathologic examination and
tissue cultures (either lung biopsy or immediate post mortem obtained samples)
Several trials conclude that use of FOB techniques and quantitative cultures are
more accurate
At least 4 studies concluded that bronchoscopically directed techniques were not
more accurate for diagnosis of VAP than clinical and X-ray criteria, combined
with cultures of tracheal aspirate
Therefore no gold standard criteria exist
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CDC- Emerging Infectious Diseases, March-April 2001
Nosocomial Pneumonia
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Differential diagnosis
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ARDS
Pulmonary edema
Pulmonary embolism
Atelectasis
Alveolar hemorrhage
Lung contusion
Nosocomial Pneumonia
Treatment
Nosocomial Pneumonia
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Antimicrobial Treatment
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Broad spectrum penicillins
3rd and 4th generation cephalosporins
Carbapenems
Quinolones
Aminoglycosides
Vancomycin
Linezolid
Inadequate
Antibiotic
Therapy
Antibiotic
Resistance
Clinical Pulmonary Infection Score (CPIS)
6
>6
Antibiotics
Ciprofloxacin
10-21 days
3 days
Randomize
Antibiotics
10-21 days
Reevaluate CPIS at 3 days
>6: treat as
pneumonia
6: discontinue
Ciprofloxacin
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
Outcomes
Variable
Ciprofloxacin
Control
(n = 39)
(n = 42)
13%
31%
.06
28%
97%
.0001
$259
$640
.0001
Death*
ABs>3d
Mean AB costs†
*At 30 days
†For patients with CPIS 6 at day 3
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
P Value
Antimicrobial Superinfections
and Resistance (S&R)
Variable
S&R
MRSA
Candida species
P aeruginosa
Ciprofloxacin
15%
5%
8%
8%
Control
35%
14%
14%
16%
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
P Value
.017
Nosocomial Pneumonia- Treatment
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Micek et al.Chest,May 2004
Randomized, controlled trial of antibiotic discontinuation for patients
with suspected VAP
Discontinuation group vs. conventional group (clinical judgment of
treating ICU physician)
Discontinuation policy(clinical criteria)
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Non-infectious etiology identified or
Signs and symptoms suggestive of infection had resolved (fever,
leukocytosis, purulent sputum, PaO2/FiO2 ratio > 250, improvement of
CXR)
Only statistically different outcome was duration of antibiotic therapy
Mortality, length of ICU stay and 2nd episode of VAP were similar in
both groups
Proposed Strategy for Management of Suspected Ventilator-Associated Pneumonia
Torres, A. et al. N Engl J Med 2004;350:433-435
Treatment of Nosocomial Pneumonia
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Vancomycin versus Linezolid for MRSA pneumonia
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Rubinstein et al. CID2001;32:402-12
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Randomized, double blinded, multi-center study
203 patients received Linezolid /193 patients received Vancomycin
Clinical success equivalent( 66.4% linezolid vs.68.1% Vancomycin)
Microbiological success equivalent (67.9% Linezolid and 71.8%Vanc)
VRE in stools (0% linezolid vs. 4% Vancomycin)
Treatment of Nosocomial Pneumonia
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Vancomycin versus Linezolid for MRSA infections/pneumonia
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Stevens et al. CID 2002; 34:1481-90
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Randomized, open label study
460 patients
Clinical success equivalent( 73.2% linezolid vs.73.1% Vancomycin)
Microbiological success equivalent (58.9% Linezolid and 63.2%Vanc)
GI side effects higher in the Linezolid arm
Treatment of Nosocomial Pneumonia
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Vancomycin versus Linezolid for MRSA pneumonia
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Wunderink RG et al.Chest Nov.2003
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Retrospective analysis of 2 prospective double blind multinational
studies
160 patients with MRSA VAP received Linezolid or Vancomycin
Outcome assessed 12-28 days post treatment
Logistic regression analysis used to determine the effect of treatment,
and other baseline variables on outcome
Cure rates showed linezolid to be superior ( 59% Linezolid vs.35.5%
Vancomycin, p=0.009))
Survival rates favored Linezolid (80% Linezolid vs. 63.5% Vancomycin,
p=0.03)
Linezolid vs. Vancomycin for VAP
80
70
60
Linezolid
Vancomycin
50
40
30
20
10
0
Cure
rate
Survival
rate
Nosocomial Pneumonia
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Duration of antimicrobial treatment
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Optimal duration of treatment has not been
established
Most experts recommend 14-21 days of treatment
Recent data support shorter treatment regimens
(8 days)
Treatment of Nosocomial Pneumonia
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Comparison of 8 vs.15 days of antibiotics for VAP
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Prospective, randomized, double blind clinical trial
51 French ICUs
401 patients with VAP (quantitative culture results)
Clinical effectiveness comparable, with the possible exception of
VAP caused by non fermenting GNR
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JAMA 290 No 19, November 2003
Treatment of Nosocomial Pneumonia
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42
39
36
33
30
27
24
21
18
15
12
9
6
3
0
8days
15 days
Mortality
Recur
Infec
P.aerug Abx Free
Days
Nosocomial Pneumonia
Prevention
Nosocomial pneumonia- Surveillance
#Vent Days/
#Patient Days
Ventilator Utilization Rate
0.7
0.65
0.6
0.55
0.5
0.45
0.4
0.35
0.3
Ventilator Utilization Rate
NNIS 25th percentile (0.37)
NNIS 50th percentile (0.47)
NNIS 75th percentile (0.53)
3qtr 2003
4qtr 2003
1qtr 2004
2qtr 2004
Quarter/Year
# VAP/
1000 Ventilator Days
Ventilator Associated Pneumonias*
12
10
8
Ventilator Associated
Pneumonias
6
NNIS 25th percentile (2.4)
4
NNIS 50th percentile (5.1)
2
0
3qtr 2003
4qtr 2003
1qtr 2004
2qtr 2004`
NNIS 75th percentile (11.8)
Quarter/Year
*Ventilator associated pneumonia benchmarks include only data from January 2002-June 2003. The number of pneumonias and ventilator days is a relatively small sampling and the data should be considered
provisional.
Quarter/Year
3qtr 2003
4qtr 2003
1qtr 2004
2qtr 2004
Last 4 qtrs
# Infections
2
0
0
2
#Ventilator Days
340
394
347
298
1379
# Vent pneumonia/1000 vent days
0.0
5.1
0.0
0.0
1.5
Nosocomial Pneumonia
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Preventive Measures
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Incentive spirometry
Promote early ambulation
Avoid CNS depressants
Decrease duration of immunosupression
Infection control measures
Educate and train personnel
Nosocomial Pneumonia
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Preventive Measures
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Avoid prolonged nasal intubation
Suction secretions
Semi-recumbent position( 30-45°head elevation)
Do not change ventilator circuits routinely more
often than every 48 hours
Drain and discard tubing condensate
Use sterile water for respiratory humidifying
devices
Subglottic secretions drainage
Craven, et al. Chest. 1995;108:s1-s16.
Nosocomial Pneumonia
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Preventive Measures
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Remove NGT when no longer needed
Avoid gastric overdistention
Stress ulcer prophylaxis:
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Acidification of enteral feedings
Prophylactic antibiotics
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sulcrafate; antacids; H2 receptor antagonists
Inhaled antibiotics
Selective digestive decontamination
Chlorexidine oral rinses
Vaccines ( Influenza; Strep.pneumoniae)
Bibliography
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MMWR, January 3,1997/vol.46/No.RR-1
Infectious Disease Clinics of North America- December 2003
American J. Resp. Crit Care Medicine Vol. 165, 2002: 867- 903
NEJM Volume 340: 627-634, 1999
Am J Resp Crit Care Med 1995:153:1711.
ATC Guidelines : Hospital-acquired pneumonia in adults
Annals Int. Med.Vol.129,No 6:433-440, 1998
NEJM Volume 344:665-671, 2001
Chest/120/3/September 2001
Bibliography
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Thorax; 57:366-371, 2002
NEJM Vol. 350: 433-35, 2004
Emerging Infectious Diseases Vol. 7,No 2, 2001
Up To Date: Diagnosis of ventilator-associated pneumonia,
March 2004
Chest /125/5/Pages 1791-1799 and 1600-1601, May 2004
JAMA vol.290, No 19, November 19, 2003
Chest 124(5):1789-97,November 2003
AntimicrobAgentsChemother 47(11):3442-7, 2003
Bibliography
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Intensive Care Medicine2004Mar;30(3):343-6
Am J Resp Crit Care Med 162(2):505-511, 2000
CID 32:402-412, February 2001
Crit. Care Med.vol.32(1):137-143, January 2004
Am J Resp Crit Care Med vol.168:173-179, 2003
Chest/117:1434-42/September 2000