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