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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 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
Copyright © 2001 ican, INC.
Richards, et al. Crit Care Med. 1999;27:887-892.
Site Distribution in Adult ICUsMajor Types of Infection (NNIS data, 1992-1997)
27%
GI
CVS
Other
Pneu
31%4%
4%
EENT
BSI19%
5%
6%LRTI 4%
UTI
Urinary tract infections (UTI)
Pneumonia (Pneu)
Primary bloodstream infections (BSI)
Gastrointestinal infections (GI)
Cardiovascular system (CVS)
Eye, ear, nose, and throat infection (EENT)
Lower respiratory infections (LRTI) (other than pneumonia)
OtherN = 14,177
Nosocomial Pneumonia
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
Ho
spit
al M
ort
alit
y (%
)
0
10
20
30
40
50
None Early Onset Late Onset
Nosocomial Pneumonia
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
*
**
Nosocomial Pneumonia Hence, the importance of focusing
on: Accurate diagnosis Appropriate treatment Preventive measures
Nosocomial Pneumonia Pathogenesis Risk factors Etiologic agents Differential diagnosis Treatment Prevention
Nosocomial Pneumonia
Pathogenesis
Nosocomial Pneumonia 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 Pathogenesis
Invasion of the lower respiratory tract by:
Aspiration of oropharyngeal/GI organisms Inhalation of aerosols containing bacteria Hematogenous spread
Colonization Aspiration
HAP
MRSA*
Nosocomial Pneumonia
Risk Factors
Nosocomial Pneumonia 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.
Nosocomial Pneumonia 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.
Nosocomial Pneumonia
Etiologic Agents
Nosocomial Pneumonia Etiologic Agents
S.aureus Enterobacteriaceae P.aeruginosa Acinetobacter sp. Polymicrobial Anaerobic bacteria Legionella sp. Aspergillus sp. Viral
No
soco
mia
l P
neu
mo
nia
(%
)
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 aeruginosaOSSA = Oxacillin-sensitive
S aureusORSA = Oxacillin-resistant
S aureusES = Enterobacter
speciesSM = S marcescens
Pathogens Associated With HAP
Ibrahim, et al. Chest. 2000;117:1434-1442.
Nosocomial Pneumonia
Diagnosis
Nosocomial Pneumonia 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
Nosocomial Pneumonia 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 (>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
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
Nosocomial Pneumonia Differential diagnosis
ARDS Pulmonary edema Pulmonary embolism Atelectasis Alveolar hemorrhage Lung contusion
Nosocomial Pneumonia
Treatment
Nosocomial Pneumonia Antimicrobial Treatment
Broad spectrum penicillins 3rd and 4th 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: discontinueCiprofloxacin
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)
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
Antimicrobial Superinfections and Resistance (S&R)
S&R 15% 35% .017MRSA 5% 14%Candida species 8% 14%P aeruginosa 8% 16%
Variable Ciprofloxacin Control P Value
Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.
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 2nd 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)
Treatment of Nosocomial Pneumonia
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
Treatment of Nosocomial Pneumonia
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
Curerate
Survivalrate
LinezolidVancomycin
Nosocomial Pneumonia 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)
Treatment of Nosocomial Pneumonia
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
Treatment of Nosocomial Pneumonia
0369
121518212427303336394245
Mortality RecurInfec
P.aerug Abx Free Days
8days15 days
Nosocomial Pneumonia
Prevention
Nosocomial pneumonia- Surveillance
Ventilator Utilization Rate
0.30.350.4
0.450.5
0.550.6
0.650.7
3qtr 2003 4qtr 2003 1qtr 2004 2qtr 2004
Quarter/Year
#V
en
t D
ays/
#P
ati
en
t D
ays
Ventilator Utilization Rate
NNIS 25th percentile (0.37)
NNIS 50th percentile (0.47)
NNIS 75th percentile (0.53)
Ventilator Associated Pneumonias*
0
2
4
6
8
10
12
3qtr 2003 4qtr 2003 1qtr 2004 2qtr 2004`
Quarter/Year
# V
AP
/
10
00
Ve
nti
lato
r D
ays
Ventilator AssociatedPneumonias
NNIS 25th percentile (2.4)
NNIS 50th percentile (5.1)
NNIS 75th percentile (11.8)
*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 0.04qtr 2003 2 394 5.11qtr 2004 0 347 0.02qtr 2004 0 298 0.0Last 4 qtrs 2 1379 1.5
Nosocomial Pneumonia Preventive Measures
Incentive spirometry Promote early ambulation Avoid CNS depressants Decrease duration of immunosupression Infection control measures Educate and train personnel
Nosocomial Pneumonia Preventive Measures
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 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