HEALTHCARE-ASSOCIATED PNEUMONIA: EPIDEMIOLOGY, PATHOGENESIS & PREVENTION 2014 David Jay Weber, M.D.,...

HEALTHCARE-ASSOCIATED PNEUMONIA: EPIDEMIOLOGY,

PATHOGENESIS & PREVENTION 2014

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

HAZARDS IN THE ICU

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

TOPICS: HCAP, HAP, VAP

Epidemiology Impact of healthcare-associated infections Definitions NHSN surveillance definitions Incidence and prevalence of HCAP, HAP, VAP

Pathogenesis Mechanisms of pneumonia Microbiology Risk factors Diagnosis

Prevention

GOALS OF LECTURE

Understand the epidemiology of nosocomial pneumonia Impact Incidence Risk factors for acquisition and mortality

Understand the pathophysiology of HAP & VAP Microbiology Diagnosis Treatment

Understand methods of prevention

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

site-specific criterion were first present together on or after the 3rd 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

VENTILATOR-ASSOCIATED EVENTS (VAE) SURVEILLANCE ALGORITHM

VENTILATOR-ASSOCIATEDCONDITION (VAC)

INFECTION-RELATED VENTILATOR-ASSOCIATED COMPLICATIONS (IVAC)

POSSIBLE VENTILATOR-ASSOCIATED PNEUMONIA (VAP)

PROBABLE VENTILATOR-ASSOCIATED PNEUMONIA (VAP)

THRESHOLD VALUES FOR CULTURED SPECIMENS USED IN THE PROBABLE VAP DEFINITION

NHSN DEFINITIONS OF HAP AND VAP (children, <18 years of age)

Table 1. Specific site algorithms for clinically defined pneumonia (PNU1)

Table 2. Specific site algorithms for pneumonia with common bacterial or filamentous fungal pathogens and specific laboratory findings (PNU2)

Table 3. Specific site algorithms for viral, Legionella, and other bacterial pneumonias with definitive laboratory findings (PNU2)

Table 4. Specific site algorithm for pneumonia in immunocompromised patients (PNU3)

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

HAP & VAP: IMPACT

Potential complications of mechanical ventilation Pneumonia, acute respiratory distress syndrome (ARDS), pulmonary

embolism, barotrauma, pulmonary edema, and death

Complications result in longer ICU stays, increased costs, and increased risk of disability and death Mortalioty in patient with acute lung injury, estimated to range from 24% in

patients 15-19 years of age to 60% for patients >85 years of age Prevalence: 2010 NHSN = 3,525 cases of VAP Incidence: 2010 NHSN = 0.0-5.8 per 1,000 ventilator days

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

HAP: IMPACT

Accounts for ~15% of all healthcare-associated infections (3rd most common cause of HAIs after UTIs and SSIs) Accounts for ~25% of all nococomial infections in the ICU (50%

of antibiotics provided) Number of cases per year: ~275,000 Prevalence

VAP develops in 10% to 20% of mechanically ventilated patients

VAP rate = 1-4 cases/1,000 ventilator-days

HAP: IMPACT

Cost Increases hospital stay by an average of 7-11 days Cost per patient >$40,000 Direct cost (estimated) of excess hospital stays = $1.5 billion/year

Mortality Crude mortality: 30-70% (average 40%) Attributable mortality: 33-50%

Deaths Deaths directly caused by infection: 7,085 (3.1%) Deaths to which infection contributed: 22,983 (10.1%)

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 infectionRespiratory 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

VAP: TIME COURSE

Cumulative Incidence ICU VAP

0%

10%

20%

30%

40%

50%

60%

5 10 15 20 25 30

Garrard C. Chest 1995;108:17S

Days

VAP: TIME COURSE

Mean Daily Risk Of VAP

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

0-5 6-136 11-15 16-20 21-25 26-30

Days

TOP 7 PATHOGENS ASSOCIATED WITH VAP: NHSN, 200

0% 5% 10% 15% 20% 25% 30%

Other

Serratia spp.

E. coli

Acinetobacter

Enterobacter spp.

Klebsiella pneumoniae/oxytoca

P. aeruginosa

S. aureus

Sievert DM. ICHE 2013; 34;1-14

Pathogen NNIS INVASIVE DXS. 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% 14.15Pseudomonas 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%

ETIOLOGIC AGENTS ASSOCIATED WITH HAP: NNIS vs INVASIVE DX

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

Fridkin SK. Crit Care Med 2001;29:N67

Open bars <7 days hospitalizationClosed bars >7 days hospitalization

PATHOGENS AS A FUNCTION OF DURATION OF HOSPITALIZATION

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

Antibiotic-Resistant VAP

Prior MV>7 days 60.009

Prior ABs 13<0.001

Broad ABs 40.025

0

5

10

15

20

25

–/– –/+ +/– +/+

MV>7 Days/Prior Antibiotics

Org

an

ism

(%

)

P aeruginosaAcinetobacter baumanniiMRSA

MV = Mechanical ventilation.MRSA = Methicillin-resistant S aureus.

Trouillet JL, et al. Am J Respir Crit Care Med. 1998;157:531-539.

Variable OddsRatio P Value

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

0

5

10

15

20

25

30

CAP HCAP HAP VAP

Kollef MH, et al. Chest 2005;128:3854

10.0 19.8 18.8 29.3

P > 0.05

P < 0.0001

P < 0.001

METHODS OF DIAGNOSIS

Clinical findings (symptoms, signs) Blood, pleural fluid analysis & cultures, tissue diagnosis Non-bronchoscopic

Endotracheal aspiration Percutaneous needle aspiration Blind bronchial sampling (“Blind” BAL)

Bronchoscopic techniques Protected specimen brush (PSB) Bronchoalveolar lavage (BAL)

CLINICAL DIAGNOSIS

Symptoms and signs: Fever, respiratory distress Chest radiography: Infiltrate, consolidation, cavity Laboratory: Leukocytosis, leukopenia Sputum: Purulence (WBC), culture Clinical diagnosis (ATS/IDSA)

New or progressive infiltrate >2 of the following: Temperature >38 oC, leukocytosis or

leukopenia, purulent secretions

DIFFERENTIAL DIAGNOSIS:FEVER AND PULMONARY INFILTRATES

Pulmonary infection Pulmonary embolism Pulmonary drug reaction Pulmonary hemorrhage Chemical aspiration Sepsis with acute respiratory distress syndrome Drug reaction

DIAGNOSING VAP PNEUMONIAD IAG N O SIN G NO SO C O M IA L PN EU M O NIA (M eduri G , et al. Chest 1994;106:221)

50patients completed

the study

14concomitant

infections

19pneumonia

11concomitant

infections

14sinusitis

catheter infectionurinary tract infection

0concomitant

infections

candidemiacholecystitis

empyemaperitonitis

37infectious

5 fibroproliferation1 chemical aspiration

6pulmonary

1 pancreatitis1 drug fever

2extra-pulmonary

8noninfectious only

45patients with a

definitive sourceof fever identified

INDICATIONS FOR INVASIVE DIAGNOSIS

Routine for all patients with possible nosocomial pneumonia?

Targeted use of invasive diagnosis Critically ill Immunocompromised patient (esp. T-cell defect) Deterioration on empiric therapy Failure to respond to empiric therapy Other therapeutic consideration (e.g., foreign-body)

PROTECTED SPECIMEN BRUSH

BRONCHOALVEOLAR LAVAGE

Meta-analysis of Invasive Strategies for the Diagnosis of Ventilator-Associated Pneumonia & their Impact on Mortality*

Odds Ratio for Mortality

*Random effects model; Test of heterogeneity p=0.247, for Odds ratio p=0.620

0.13 1 7.84

Study % Weight Odds Ratio

(95% CI)

2.42 (0.75,7.84) Sanchez-Nieto, et al. 13.0 0.71 (0.28,1.77) Ruiz, et al. 19.5 0.71 (0.47,1.06) Fagon, et al. 50.9 1.08 (0.39,2.98) Violan, et al. 16.5

0.89 (0.56,1.41) Overall (95% CI)

Favors InvasiveApproach

Favors Non-InvasiveApproach

Shorr A, Kollef. MH Crit Care Med 2005;33:46.

Morrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-352

EMPIRIC THERAPY: GENERAL RULES

Know the flora and susceptibilities of the pathogens causing nosocomial pneumonia at your own institution

Obtain history of antibiotic-allergies from all patients (adjust regimen appropriately)

Choose empiric therapy to minimize drug interactions Dose adjust (when appropriate) in patients with renal and/or hepatic

failure Consider specific contraindications or precautions (e.g., pregnancy,

neuromuscular disease) All other things being equal use the least expensive therapy Provide appropriate non-antibiotic care

IMPACT OF ANTIMICROBIALSIMPACT OF ANTIMICROBIALS

0

10

20

30

40

50

60

Hospital Mortality

%

All Cause Infection-related

Inadequate Therapy n = 169

Adequate Therapy n = 486

Kollef Chest 115:462, 1999

HAP: The Importance of Initial Empiric Antibiotic Selection

Alvarez-Lerma F. Intensive Care Med 1996 May;22(5):387-394. Rello J, Gallego M, Mariscal D, et al. Am J Respir Crit Care Med 1997 Jul;156(1):196-200.Luna CM, Vujacich P, Niederman MS, et al. Chest 1997;111(3):676-685.Kollef MH and Ward S. Chest 1998 Feb;113(2):412-20.Sanchez-Nieto JM, Torres A, Garcia-Cordoba F, et al. Am J Respir Crit Care Med. 1998;157:371-376.Ruiz M, Torres A, Eqig, S, et al. Am J Respir Crit Care Med. 2000;162:119-125.Dupont H, Mentec H, Sollet, JP, et al. Intensive Care Med. 2001;27(2):355-362 61

16.2

41.538

33.3

25

39

47.3

24.7

63

91

61.4

4350

60.7

0

20

40

60

80

100

Alvarez-Lerma

Rello Luna Kollef Sanchez-Nieto

Ruiz Dupont

% m

ort

ality

Adequate init. antibiotic Inadequate init. antibiotic

P=NS P=NSP=NSP=NSP=0.001P<0.001P=0.06

ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416

Vincent J-L, et al. Drugs 2010;70:1927-1944

ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416

DURATION OF THERAPY: STUDY DESIGN

Authors: Chastre J, et al. JAMA 2003;290:2988 Study goal: Compare 8 vs 15 days of therapy for VAP Design: Prospective, randomized, double-blind (until day 8),

clinical trial VAP diagnosed by quantitative cultures obtained by bronchoscopy

Location: 51 French ICUs (N=401 patients) Outcomes: Assessed 28 days after VAP onset (ITT analysis)

Primary measures = death from any cause Microbiologically documented pulmonry infection recurrence Antibiotic free days

DURATION OF THERAPY: RESULTS

Primary outcomes (8 vs 15 days) Similar mortality, 18.8% vs 17.2% Similar rate of recurrent infection, 28.9% vs 26.0%

MRSA, 33.3% vs 42.9% Nonfermenting GNR, 40.6% vs 25.4% (p<0.05)

More antibiotic free days, 13.1% vs 8.7% (p<0.001) Secondary outcomes (8 vs 15 days)

Similar mechanical ventilation-free days, 8.7 vs 9.1 Similar number of organ failure-free days, 7.5 vs 8.0 Similar length of ICU stay, 30.0 vs 27.5 Similar frequency death at day 60, 25.4% vs 27.9% Multi-resistant pathogen (recurrent infection), 42% v 62% (p=0.04)

THERAPY: SUMMARY I

Negative lower respiratory tract cultures can be used to stop antibiotic therapy if obtained in the absence of an antibiotic change in past 72 hours

Early, appropriate, broad spectrum therapy, antibiotic therapy should be prescribed with adequate doses to optimize antimicrobial efficacy

An empiric therapy regimen should include agents that are from a different antibiotic class than the patient is currently receiving

De-escalation of antibiotic should be considered once data are available on the results of the patient’s cultures and clinical response

A shorter duration of therapy (7-8 days) is recommended for patients with uncomplicated HAP, VAP, or HCAP who have had a good clinical response

THERAPY: SUMMARY III

High risk patients Multiple-drug regimens required Combine beta-lactam with aminoglycoside (preferred)

or quinolone (levo or cipro) Consider need for coverage of oxacillin-resistant S.

aureus, Legionella

THERAPY: SUMMARY IV

Bronchoscopy directed therapy May improve outcome

Demonstrated by a randomized study Several cohort studies have failed to demonstrated benefit

Mortality reduced by initial use of appropriate antibiotics Duration of therapy, in general, should be 7-8 days

Kollef M. Chest 2004;32:1396

Morrow LE, Kollef MH. Crit Care Med 2010;38[suppl]:S352-352

STRENGTH OF RECOMMENDATIONSAND QUALITY OF EVIDENCE

STRATEGIES TO PREVENT VAPIN ACUTE CARE HOSPITALS

Surveillance Definition of VAP most subjective of all device associated HAIs Significant intra-observer variability exists Use active surveillance (not administrative data alone) Ideally perform semiquantitative culture of endotracheal

secretions or quantitative culture of BAL fluid Prevention

Follow CDC guidelines to prevent VAP Interrupt most common mechanisms by which VAP develops

Aspiration of secretionsColonization of the aerodigestive tractUse of contaminated equipment

Coffin SE, et al. ICHE 2008;29 (suppl 1):S31-S40


Prevention: General strategies Conduct active surveillance Adhere to hand hygiene recommendations Use non-invasive ventilation whenever possible Minimize the duration of ventilation Perform daily assessments of readiness to wean Educate personnel regarding prevention

Prevention: Strategies to prevent aspiration Maintain patients in a semirecumbent position (30o-45o

elevation) Use a cuffed ET tube with in-line or subglottic suctioning



Prevention: Strategies to reduce colonization Orotracheal intubation preferred to nasotracheal intubation Avoid acid suppressive therapy Perform oral care with an antiseptic solution

Prevention: Strategies to minimize contamination Use sterile water to rinse reusable respiratory equipment Remove condensate from the ventilatory circuit Change the ventilatory circuit only when visibly soiled or

malfunctioning Store and disinfect respiratory equipment properly



Special approached for the prevention of VAP Use an ET tube with in-line and subglottic suctioning

Approaches that should not be routinely used Do not routinely administer IVIG, GM-CSF, or chest physiotherapy Do not routinely use rotational therapy with kinetic or continuous

lateral rotational therapy beds Do not routinely administer prophylactic aerosolized or systemic

antimicrobials Unresolved issues

Selective digestive tract decontamination Avoidance of H2 antagonists or proton pump inhibitors Use of antiseptic-impregnated ET tubes


IHI GUIDELINE: VAP BUNDLE

Elevation of the head of the bed to between 30 and 45 degrees

Daily “sedation vacation” and daily assessment of readiness to extubate

Peptic ulcer disease (PUD) prophylaxis Deep venous thrombosis (DVT) prophylaxis (unless

contraindicated)

CONCLUSIONS I

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

Local epidemiology of pathogens and antibiograms are critical to empiric and directed chemotherapy

Determining the etiologic agent(s) of nosocomial pneumonia is problematic even with new invasive diagnostic techniques

CONCLUSIONS II

Use of empiric, broad-spectrum regimens remain critical to favorable patient outcomes

Single-drug regimens may be appropriate for some low-risk patients, but two-drug regimens with broad spectrum (including P. aeruginosa) are necessary for high-risk patients

Prevention is superior to treatment

HEALTHCARE-ASSOCIATED PNEUMONIA: EPIDEMIOLOGY, PATHOGENESIS & PREVENTION 2014 David Jay Weber, M.D.,...

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