Nosocomial Pneumonia Eliane Haron M D Nosocomial Pneumonia

Nosocomial Pneumonia Eliane Haron, M. D.

Nosocomial Pneumonia Epidemiology n n n 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 n n n 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 Hospital Mortality (%) 50 P =. 504 * * 40 30 20 10 0 *Upper 95% confidence interval * None Early Onset Late Onset Nosocomial Pneumonia Ibrahim, et al. Chest. 2000; 117: 1434 -1442.

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

Nosocomial Pneumonia n n n Pathogenesis Risk factors Etiologic agents Differential diagnosis Treatment Prevention

Nosocomial Pneumonia Pathogenesis

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

Colonization Aspiration MRSA* HAP

Nosocomial Pneumonia Risk Factors

Nosocomial Pneumonia n Risk Factors n Host Factors n n 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 n admission to an ICU, administration of antibiotics, chronic lung disease, endotracheal intubation, etc.

Nosocomial Pneumonia n Risk Factors n Conditions favoring aspiration or reflux n n Mechanical ventilation n n 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 n 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 n Etiologic Agents n n n n n S. aureus Enterobacteriaceae P. aeruginosa Acinetobacter sp. Polymicrobial Anaerobic bacteria Legionella sp. Aspergillus sp. Viral

Pathogens Associated With HAP Nosocomial Pneumonia (%) 40 P =. 003 Early-onset NP 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 n Diagnosis n n Not necessarily easy to accurately diagnose HAP Criteria frequently include: n Clinical n n Radiographic n n new or progressive infiltrates on CXR, Laboratorial n n fever ; cough with purulent sputum, leukocytosis or leukopenia Microbiologic n n Suggestive gram stain and positive cultures of sputum, tracheal aspirate, BAL, bronchial brushing, pleural fluid or blood Quantitative cultures

Nosocomial Pneumonia n Problems n n All above criteria fairly sensitive, but very nonspecific, particularly in mechanically ventilated patients Other criteria/problems include n n n 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 n Bronchoscopically Directed Techniques for diagnosis of VAP and Quantitative cultures n n n 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 n n 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 n CDC- Emerging Infectious Diseases, March-April 2001

Nosocomial Pneumonia n Differential diagnosis n n n ARDS Pulmonary edema Pulmonary embolism Atelectasis Alveolar hemorrhage Lung contusion

Nosocomial Pneumonia Treatment

Nosocomial Pneumonia n Antimicrobial Treatment n n n n 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) 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>3 d 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% 16% Singh, et al. Am J Respir Crit Care Med. 2000; 162: 505 -511. P Value . 017

Nosocomial Pneumonia- Treatment n n 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) n n Non-infectious etiology identified or Signs and symptoms suggestive of infection had resolved (fever, leukocytosis, purulent sputum, Pa. O 2/Fi. O 2 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

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 n Vancomycin versus Linezolid for MRSA pneumonia n Rubinstein et al. CID 2001; 32: 402 -12 n n n 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 n Vancomycin versus Linezolid for MRSA infections/pneumonia n Stevens et al. CID 2002; 34: 1481 -90 n n n 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 n Vancomycin versus Linezolid for MRSA pneumonia n Wunderink RG et al. Chest Nov. 2003 n n n 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

Nosocomial Pneumonia n Duration of antimicrobial treatment n n n 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 n Comparison of 8 vs. 15 days of antibiotics for VAP n n 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 n JAMA 290 No 19, November 2003

Treatment of Nosocomial Pneumonia

Nosocomial Pneumonia Prevention

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 3 qtr 2003 4 qtr 2003 1 qtr 2004 2 qtr 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 1. 5

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

Nosocomial Pneumonia n Preventive Measures n n n n 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: s 1 -s 16.

Nosocomial Pneumonia n Preventive Measures n n n Remove NGT when no longer needed Avoid gastric overdistention Stress ulcer prophylaxis: n n n Acidification of enteral feedings Prophylactic antibiotics n n sulcrafate; antacids; H 2 receptor antagonists Inhaled antibiotics Selective digestive decontamination Chlorexidine oral rinses Vaccines ( Influenza; Strep. pneumoniae)

Bibliography n n n n 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 n n n n 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 Antimicrob. Agents. Chemother 47(11): 3442 -7, 2003

Bibliography n n n Intensive Care Medicine 2004 Mar; 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