Hospital Acquired Pneumonia

Nosocomial Pneumonia
Eliane Haron,M.D.

Epidemiology
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
Epidemiology
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
H
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t
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y

(
%
)

0
10
20
30
40
50
None Early Onset Late Onset
P = .504 P<.001
P<.001
Mortality and Time of Presentation of HAP
Ibrahim, et al. Chest. 2000;117:1434-1442.
*Upper 95% confidence interval
*
*
*
Hence, the importance of focusing on:
Accurate diagnosis
Appropriate treatment
Preventive measures
Pathogenesis
Risk factors
Etiologic agents
Differential diagnosis
Treatment
Prevention
Pathogenesis
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
Pathogenesis
Invasion of the lower respiratory tract by:
Aspiration of oropharyngeal/GI organisms
Inhalation of aerosols containing bacteria
Hematogenous spread
Colonization Aspiration
HAP
MRSA*
Risk Factors
Risk Factors
Host Factors
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
admission to an ICU, administration of antibiotics,
chronic lung disease, endotracheal intubation, etc.
Risk Factors
Conditions favoring aspiration or reflux
Supine position, depressed consciousness, endotracheal
intubation, insertion of nasogastric tube
Mechanical ventilation
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
Surgical procedures that involve the head and neck,
being immobilized as a result of trauma or illness,
sedation etc.
Etiologic Agents
Etiologic Agents
S.aureus
Enterobacteriaceae
P.aeruginosa
Acinetobacter sp.
Polymicrobial
Anaerobic bacteria
Legionella sp.
Aspergillus sp.
Viral

N
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P
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a

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%
)

0
5
10
15
20
25
30
35
40
PA OSSA ORSA ES SM
P = .003
P = .043
P = .408
P = .985
P = .144
Pathogen
Early-onset NP
Late-onset NP
PA = P aeruginosa
OSSA = Oxacillin-sensitive
S aureus
ORSA = Oxacillin-resistant
S aureus
ES = Enterobacter
species
SM = S marcescens
Pathogens Associated With HAP
Ibrahim, et al. Chest. 2000;117:1434-1442.
Diagnosis
Diagnosis
Not necessarily easy to accurately diagnose HAP
Criteria frequently include:
Clinical
fever ; cough with purulent sputum,
Radiographic
new or progressive infiltrates on CXR,
Laboratorial
leukocytosis or leukopenia
Microbiologic
Suggestive gram stain and positive cultures of sputum,
tracheal aspirate, BAL, bronchial brushing, pleural fluid or
blood
Quantitative cultures
Problems
All above criteria fairly sensitive, but very non-
specific, particularly in mechanically ventilated
patients
Other criteria/problems include
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

Bronchoscopically Directed Techniques for diagnosis
of VAP and Quantitative cultures
Bronchoscopy with BAL/bronchial brushings (10,000 to
100,000 CFU/ml and less than 1% of squamous cells)

Protected specimen brush method (>10 CFU/ml)

Protected BAL with a balloon tipped catheter (>5% of
neutrophils or macrophages with intracellular organisms on
a Wright-Giemsa stain)

Nosocomial pneumonia

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

CDC- Emerging Infectious Diseases, March-April 2001
Differential diagnosis
ARDS
Pulmonary edema
Pulmonary embolism
Atelectasis
Alveolar hemorrhage
Lung contusion

Treatment
Antimicrobial Treatment
Broad spectrum penicillins
3
rd
and 4
th
generation cephalosporins
Carbapenems
Quinolones
Aminoglycosides
Vancomycin
Linezolid

Inadequate
Antibiotic
Therapy
Antibiotic
Resistance
Clinical Pulmonary Infection Score (CPIS)
Randomize
Antibiotics
10-21 days
Ciprofloxacin
3 days
Antibiotics
10-21 days
>6: treat as
pneumonia
6: discontinue
Ciprofloxacin
Reevaluate CPIS at 3 days
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
>6
6
Outcomes
Death* 13% 31% .06
ABs>3d 28% 97% .0001
Mean AB costs
$259 $640 .0001

*At 30 days
For patients with CPIS 6 at day 3

Variable Ciprofloxacin Control P Value
(n = 39) (n = 42)
Antimicrobial Superinfections
and Resistance (S&R)
S&R 15% 35% .017
MRSA 5% 14%
Candida species 8% 14%
P aeruginosa 8% 16%

Variable Ciprofloxacin Control P Value

Nosocomial Pneumonia- Treatment
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)
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 2
nd
episode of VAP were similar in
both groups

Torres, A. et al. N Engl J Med 2004;350:433-435
Proposed Strategy for Management of Suspected Ventilator-Associated Pneumonia
Treatment of Nosocomial Pneumonia
Vancomycin versus Linezolid for MRSA pneumonia

Rubinstein et al. CID2001;32:402-12
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)
Vancomycin versus Linezolid for MRSA infections/pneumonia

Stevens et al. CID 2002; 34:1481-90
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
Vancomycin versus Linezolid for MRSA pneumonia

Wunderink RG et al.Chest Nov.2003
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
0
10
20
30
40
50
60
70
80
Cure
rate
Survival
rate
Linezolid
Vancomycin
Duration of antimicrobial treatment

Optimal duration of treatment has not been
established

Most experts recommend 14-21 days of treatment

Recent data support shorter treatment regimens
(8 days)
Comparison of 8 vs.15 days of antibiotics for VAP

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

JAMA 290 No 19, November 2003
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
Mortality Recur
Infec
P.aerug Abx Free
Days
8days
15 days
Prevention
Nosocomial pneumonia- Surveillance

Ventilator Utilization Rate
0.3
0.35
0.4
0.45
0.5
0.55
0.6
0.65
0.7
3qtr 2003 4qtr 2003 1qtr 2004 2qtr 2004
Quarter/Year
#
V
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t

D
a
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s
/
#
P
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i
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D
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s
Ventilator Utilization Rate
NNIS 25th percentile (0.37)
Ventilator Associated Pneumonias*
0
2
4
6
8
10
12
3qtr 2003 4qtr 2003 1qtr 2004 2qtr 2004`
Quarter/Year
#

V
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/
1
0
0
0

V
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D
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Ventilator Associated
Pneumonias
*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 # Infections #Ventilator Days # Vent pneumonia/1000 vent days

3qtr 2003 340 0.0
4qtr 2003 2 394 5.1
1qtr 2004 0 347 0.0
2qtr 2004 0 298 0.0
Last 4 qtrs 2 1379 1.5
Preventive Measures
Incentive spirometry
Promote early ambulation
Avoid CNS depressants
Decrease duration of immunosupression
Infection control measures
Educate and train personnel

Preventive Measures
Avoid prolonged nasal intubation
Suction secretions
Semi-recumbent position( 30-45head 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.
Preventive Measures
Remove NGT when no longer needed
Avoid gastric overdistention
Stress ulcer prophylaxis:
sulcrafate; antacids; H2 receptor antagonists
Acidification of enteral feedings
Prophylactic antibiotics
Inhaled antibiotics
Selective digestive decontamination
Chlorexidine oral rinses
Vaccines ( Influenza; Strep.pneumoniae)
Bibliography
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
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

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

Hospital Acquired Pneumonia

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Hospital Acquired Pneumonia

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Nosocomial Pneumonia

$259 $640 .0001

For patients with CPIS 6 at day 3

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