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Nosocomial Pneumonia

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.

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Nosocomial Pneumonia

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  1. Nosocomial Pneumonia Eliane Haron,M.D.

  2. 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

  3. Nosocomial Pneumonia

  4. 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

  5. Mortality and Time of Presentation of HAP P<.001 P<.001 P = .504 50 * * 40 30 Hospital Mortality (%) 20 * 10 0 Early Onset None Late Onset *Upper 95% confidence interval Nosocomial Pneumonia Ibrahim, et al. Chest. 2000;117:1434-1442.

  6. Nosocomial Pneumonia • Hence, the importance of focusing on: • Accurate diagnosis • Appropriate treatment • Preventive measures

  7. Nosocomial Pneumonia • Pathogenesis • Risk factors • Etiologic agents • Differential diagnosis • Treatment • Prevention

  8. Nosocomial Pneumonia Pathogenesis

  9. 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

  10. Nosocomial Pneumonia • Pathogenesis • Invasion of the lower respiratory tract by: • Aspiration of oropharyngeal/GI organisms • Inhalation of aerosols containing bacteria • Hematogenous spread

  11. ColonizationAspiration MRSA* HAP

  12. Nosocomial Pneumonia Risk Factors

  13. 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.

  14. 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.

  15. Nosocomial Pneumonia Etiologic Agents

  16. Nosocomial Pneumonia • Etiologic Agents • S.aureus • Enterobacteriaceae • P.aeruginosa • Acinetobacter sp. • Polymicrobial • Anaerobic bacteria • Legionella sp. • Aspergillus sp. • Viral

  17. Pathogens Associated With HAP P = .003 Early-onset NP 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 Nosocomial Pneumonia (%) 20 15 P = .144 P = .985 10 5 0 SM ORSA OSSA ES PA Pathogen Ibrahim, et al. Chest. 2000;117:1434-1442.

  18. Nosocomial Pneumonia Diagnosis

  19. 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

  20. 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)

  21. 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)

  22. 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

  23. Nosocomial Pneumonia • Differential diagnosis • ARDS • Pulmonary edema • Pulmonary embolism • Atelectasis • Alveolar hemorrhage • Lung contusion

  24. Nosocomial Pneumonia Treatment

  25. Nosocomial Pneumonia • Antimicrobial Treatment • Broad spectrum penicillins • 3rd and 4th generation cephalosporins • Carbapenems • Quinolones • Aminoglycosides • Vancomycin • Linezolid

  26. Inadequate Antibiotic Therapy Antibiotic Resistance

  27. Clinical Pulmonary Infection Score (CPIS) >6 £6 Randomize Ciprofloxacin 3 days Antibiotics 10-21 days Antibiotics 10-21 days Reevaluate CPIS at 3 days £6: discontinue Ciprofloxacin >6: treat as pneumonia Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.

  28. Death* 13% 31% .06 ABs>3d 28% 97% .0001 Mean AB costs†$259 $640 .0001 Outcomes Variable Ciprofloxacin Control P Value(n = 39) (n = 42) *At 30 days †For patients with CPIS 6 at day 3 Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.

  29. S&R 15% 35% .017 MRSA 5% 14% Candida species 8% 14% P aeruginosa 8% 16% Antimicrobial Superinfections and Resistance (S&R) Variable Ciprofloxacin Control P Value Singh, et al. Am J Respir Crit Care Med. 2000;162:505-511.

  30. 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

  31. Proposed Strategy for Management of Suspected Ventilator-Associated Pneumonia Torres, A. et al. N Engl J Med 2004;350:433-435

  32. 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)

  33. 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

  34. 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)

  35. Linezolid vs. Vancomycin for VAP

  36. 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)

  37. 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

  38. Treatment of Nosocomial Pneumonia

  39. Nosocomial Pneumonia Prevention

  40. Nosocomial pneumonia- Surveillance *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 days3qtr 2003 340 0.04qtr 2003 2 394 5.11qtr 2004 0 347 0.02qtr 2004 0 298 0.0 Last 4 qtrs 2 1379 1.5

  41. Nosocomial Pneumonia • Preventive Measures • Incentive spirometry • Promote early ambulation • Avoid CNS depressants • Decrease duration of immunosupression • Infection control measures • Educate and train personnel

  42. 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

  43. Craven, et al. Chest. 1995;108:s1-s16.

  44. 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)

  45. 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

  46. 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

  47. 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

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