HEALTHCARE-ASSOCIATED PNEUMONIA: EPIDEMIOLOGY, MICROBIOLOGY & PATHOPHYSIOLOGY

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HEALTHCARE-ASSOCIATED PNEUMONIA: EPIDEMIOLOGY, MICROBIOLOGY & PATHOPHYSIOLOGY David Jay Weber, M.D., M.P.H. Professor of Medicine, Pediatrics, & Epidemiology Associate Chief Medical Officer, UNC Health Care Medical Director, Hospital Epidemiology University of North Carolina at Chapel Hill, NC, USA

HAZARDS IN THE ICU Weinstein RA. Am J Med 1991;91(suppl 3B):180S

GOALS OF LECTURE Understand the epidemiology of nosocomial pneumonia Impact Incidence Risk factors for acquisition and mortality Review the microbiology of HAP & VAP Understand the pathophysiology of HAP & VAP Diagnosis Treatment

DEFINITIONS

Marrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-S362

Chroneou A, et al. Expert Opinion 2007;8:3117-31

HEALTHCARE-ASSOCIATED PNEUMONIA HAI An infection is considered an HAI if ALL elements of a CDC/NHSN sitespecific criterion were first present together on or after the 3 rd hospital day (day of admission is Day 1). For an HAI, an element of the infection criterion must be present during the first 2 hospital days as long as it is also present on or after Day 3. All elements used to meet the infection criterion must occur within a timeframe that does not exceed a gap of 1 calendar day between elements Pneumonia (PNEU) Pneumonia is identified using a combination of radiologic, clinical and laboratory criteria. For VAP the date of the event is the date when the last element used to meet the pneumonia criteria are occurred. http://www.cdc.gov/nhsn/acute-care-hospital/vae/index.html

VENTILATOR-ASSOCIATED EVENT (adult patients >18 years of age

EPIDEMIOLOGY

HAP & VAP: IMPACT Potential complications of mechanical ventilation Pneumonia, acute respiratory distress syndrome (ARDS), pulmonary embolism, barotrauma, pulmonary edema, and death Incidence >300,000 patients receive mechanical ventilation each year in the US 10% TO 20% develop VAP 2011, an estimated 157,000 healthcare-associated pneumonias in US Mortality (VAP) Patients 15-19 years, 24%; patients >80 years of age, 60% Attributable mortality ~10%

SURGICAL SITE SUPERFICIAL 64 5% SURGICAL SITE ORGAN SPACE 184 14% Types of Infection, 2014 BLOODSTREAM INFECTION 158 12% SURGICAL SITE DEEP 51 4% URINARY TRACT INFECTION 340 26% RESPIRATORY TRACT INFECTION 269 20% OTHER 257 19% Proportion of infection types were similar to 2013. Urinary tract infections increased by 13%; surgical site infections decreased by 12%. Bloodstream, respiratory tract and other infections were within 5% of previous year s numbers.

Magill SS, et al. New Engl J Med 2014;370:1198

PREVALENCE: ICU (EUROPE) Study design: Point prevalence rate 17 countries, 1447 ICUs, 10,038 patients Frequency of infections: 4,501 (44.8%) Community-acquired: 1,876 (13.7%) Hospital-acquired: 975 (9.7%) ICU-acquired: 2,064 (20.6%) Pneumonia: 967 (46.9%) Other lower respiratory tract: 368 (17.8%) Urinary tract: 363 (17.6%) Bloodstream: 247 (12.0%) Vincent J-L, et al. JAMA 1995;274:639

PREVALENCE: ICU (WORLDWIDE) Study design: Point prevalence, 8 May 2007 75 countries, 1265 ICUs, 13,796 adult patients Frequency of infections: 7,087 (51%) Sites of infection Respiratory tract:: 4,503 (63.5%) Abdominal: 1,392 (19.6%) Bloodstream: 1,071 (15.1%) Renal/urinary tract: 1,011 (14.3%) Antibiotic therapy: 71% Pathogens of infected patients: 47% GPC, 62% GNR, 19% fungi Infected patients had higher ICU (25.3% vs 10.7%) and hospital mortality (33.1% vs 14.8%) Vincent J-L, et al. JAMA 2009;302:2333-2329

VENTILATOR-ASSOCIATED PNEU RATES, NHSN, 2012

VENTILATOR-ASSOCIATED PNEU RATES, NHSN, 2012

VAP: TIME COURSE 60% 50% 40% 30% 20% 10% 0% Cumulative Incidence ICU VAP Garrard C. Chest 1995;108:17S 5 10 15 20 25 30 Days

VAP: TIME COURSE 5.0% Mean Daily Risk Of VAP 4.0% 3.0% 2.0% 1.0% 0.0% 0-5 6-136 11-15 16-20 21-25 26-30 Days

MICROBIOLOGY

McGill S NEJM 2014; 370: 1198

ETIOLOGIC AGENTS ASSOCIATED WITH HAP: NNIS vs INVASIVE DX Pathogen NNIS INVASIVE DX S. aureus (ORSA 55.7%) 19% 20.4% S. Pneumoniae NA 4.1% Streptococcus spp. 3% 8.0% Coagulase-negative staphylococcus 2% 1.4% Enterobacteriaceae 26% 14.15 Pseudomonas aeroginosa 17% 24.4% Acinetobacter spp. 4% 7.9% Stenotrophomonas maltophilia <1% 1.7% Hemophilus spp. 7.1% 9.8% Neisseria spp. <1% 2.6% Anaerobes 2% 0.9% Fungi 7% 0.9% Other (<1% each) 3.8% Chastre J, Fagon J-Y. Am J Respir Crit Care Med 2002;165:867-903

MICROBIOLOGY Determinants of pathogens Setting Prior antibiotic use Duration of hospitalization Early (<5 days): S. pneumoniae, H. influenzae, MSSA Late (>5 days): P. aeruginosa, MRSA, Gram (-) bacilli ICU stay Colonization

COMMON PATHOGENS BY PRESENCE OR ABSENCE OF RISK FACTORS FOR MDROs Vincent JL, et al. Drugs 2010;70:1927-1944

Weber DJ, et al. ICHE 2007;28:825-831

ICU (NNIS, 1989-99): Ventilator-Associated Pneumonia Open bars <7 days hospitalization Closed bars >7 days hospitalization Fridkin SK. Crit Care Med 2001;29:N67

PATHOGENS AS A FUNCTION OF DURATION OF HOSPITALIZATION Weber DJ, et al. ICHE 2007;28:825-831

Antibiotic-Resistant VAP Variable Odds Ratio P Value Prior MV >7 days 6 0.009 Organism (%) 25 20 15 10 Prior ABs 13 <0.001 Broad ABs 4 0.025 0 MV = Mechanical ventilation. MRSA = Methicillin-resistant S aureus. 5 P aeruginosa Acinetobacter baumannii MRSA / /+ +/ +/+ MV>7 Days/Prior Antibiotics Trouillet JL, et al. Am J Respir Crit Care Med. 1998;157:531-539.

PATHOPHYSIOLOGY

PATHOGENESIS Colonization, aspiration, pneumonia in the setting of impaired host defenses Inhalation Instillation Bacteremic spread Contiguous spread

Kollef MH, et al. Chest 2004;32:1396

VAP: RISK FACTORS Intrinsic Risk Factors Chronic lung disease/copd Severity of illness ARDS Witnessed aspiration Age >60 years Coma Head trauma/icp monitoring Upper abdominal surgery Thoracic surgery Fall-winter season Extrinsic Risk Factors Duration of intubation Emergent intubation Reintubation Elevated gastric ph Prior antibiotic therapy Nasogastric tube Enteral nutrition Supine head position Patient transport out of ICU Kollef M. Crit Care Med 2004;32:1396 (adapted)

%Hospital Mortality by Classification 30 25 20 P < 0.0001 P < 0.001 P > 0.05 15 10 5 0 10.0 19.8 18.8 29.3 CAP HCAP HAP VAP Kollef MH, et al. Chest 2005;128:3854

RISK FACTORS FOR MORTALITY (VAP) High risk pathogens: P.aeruginosa, Acinetobacter, S. maltophilia - 65% (Kollef, Chest 1995;108:165) Severity of underlying illness; shock Age Inappropriate antibiotic therapy Bilateral infiltrates Duration of prior hospitalization Prior antibiotic therapy Supine head position in ventilated patients

CONCLUSIONS Nosocomial pneumonia remains an important cause of patient morbidity and mortality in the US Nosocomial pneumonia results in a more prolonged hospital stay and increased cost

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