New Canadian Guidelines for HospitalAcquired Pneumonia HAP

1
New Canadian Guidelines for Hospital-Acquired
Pneumonia (HAP) Ventilator-Associated Pneumonia
(VAP)

• Dr. Coleman Rotstein
• University of Toronto
• University Health Network
• Toronto, Ontario

2
Disclosure Statement

• Financial Conflicts of Interest
• Grant/Research Support
• Astellas, Basilia, Johnson Johnson, Pfizer,
  Wyeth, Merck, Schering
• Consultant
• Astellas, Bayer, Merck, Pfizer, Schering, Wyeth
• Speakers Bureau
• Bayer, Merck, Pfizer, Wyeth

3
Guideline Formulation Participants

• Association of Medical Microbiology and
  Infectious Disease Canada (AMMI Canada)
• Canadian Thoracic Society (CTS)
• Intensivists
• Pharmacists

4
Epidemiology of HAP-VAP
5
Hospital-Acquired Pneumonia (HAP) Definitions

• HAP
• Arises 48 hours or more after hospital admission
• Is not incubating at the time of admission
• Ventilator-associated pneumonia (VAP)
• Arises 48-72 hours or more after endotracheal
  intubation
• Healthcare-associated pneumonia (HCAP)
• Arises within 90 days of having been admitted to
  an acute care facility pt. has resided in a
  nursing home or LTCF.

(American Thoracic Society/IDSA. Am J Respir Crit
Care Med 2005171388-416)
6
HAP Impact
Incidence

• Accounts for 15 of all nosocomial infections
  (2nd most common cause of NIs after UTIs)
• Number of cases per year in US 275,000
• Extra days in the hospital 4-9 days
• Average extra days in ICU 4.3 days
• Direct cost (estimated) of excess hospital stay
  1.5 billion per year

7
Hospital Location Relative Frequency of HAP
VAP
HAP
ICU
Non-ICU HAP 62.5
VAP 86
ICU HAP 37.5
HAP 14
Non-ICU HAP ICU HAP VAP ICU HAP
(Kumpf G et al. J Clin Epidemiol
199854495-502) (Lizioli A et al. J Hosp Infect
200354141-148) (Richards MJ et al. Crit Care
Med 199927887-892)
8
INCIDENCE OF NOSOCOMIAL INFECTIONS IN COMBINED
MEDICAL-SURGICAL ICUs

• Medical Patients Surgical Patients
• Pneumonia 30 Pneumonia
  33
• UTI 30 UTI 18
• Bloodstream SSTI 14
• infection 16 Bloodstream
• Lower resp. infection
  13
• tract 6 Lower resp.
• (not pneumonia) tract 6
• (not pneumonia)
• (Richards et al. Infect Control Hosp Epidemiol
  200021510-515)

9
Risk Factors for HAP VAP
10
Risk Factors for HAP/VAP
(Mehta RM. J Intensive Care Med 200318175-88)
(Patel PJ, et al. Seminar Respir Crit Care Med
200223415-25) (American Thoracic Society. Am J
Respir Crit Care Med 2005171388-416)
11
Pathogenesis of HAP/VAP
12
Pathogenesis of HAP/VAP
13
Pathogenesis of VAP
Endogenous and Exogenous Sources
14
Causative Pathogens
15
Classification of HAP VAP Risk Stratification
Time from Hospitalization (days)
Late-onset HAP
Early-onset HAP
Time from Intubation (days)
Early-onset VAP
Late-onset VAP
(American Thoracic Society. Am J Respir Crit Care
Med 2005171388-416)
16
Pathogens to Consider When Treating HAP/VAP
(American Thoracic Society/IDSA. Am J Respir Crit
Care Med 2005171388-416)
17
Frequency of bacterial pathogens in HAP in North
America 2,712 strains (SENTRY, Antimicrobial
Surveillance Program, Jan.-June 2000)
(Hoban DJ et al. Diag Microbiol Infect Dis
200345279-285)
18
Microbiology of Ventilator-Associated Pneumonia
at Three Barnes-Jewish Christian HealthCare
Hospitals (Teaching, Community Pediatric),
1998-2001 (N753 Episodes)
(Babcock HM et al. Infect Control Hosp
Epidemiol 200324853-858)
19
Diagnosis of HAP
20
Diagnosis of HAP/VAP

• Clinical approach
• Vs.
• Invasive approach

21
Non-invasive Strategy for Diagnosing HAP/VAP

• Clinical approach
• New lung infiltrate
• new onset fever, leukocytosis or purulent sputum
• non-quantitative bacterial analysis of
  endotracheal aspirate
• Drawback relatively non-specific for HAP
• Heyland et al. demonstrated adequacy of clinical
  criteria for VAP diagnosis in RCT (BAL with
  quantitation vs. non-quantitative endotracheal
  aspirate) no difference in 28 d mortality or LOS
  in ICU or hospital

(ATS, Am J Respir Crit Care Med
19961531711-1725) (Helling TS, Van Way C,
Krantz S, et al. Am J Surg 1996171570-575) (Hubm
ayr RD et al ATS Consensus Statement Intensive
Care Med 2002281521-1536) (Canadian Critical
Care Trials Group. NEJM 20063552619-2630)
22
Diagnosis of VAP in the ICUQuantitative BAL vs.
Nonquantitative Endotracheal Aspirate (ETA)
74.2
74.6
Response
18.9
18.4
12.3d
12.2d
10.4d
10.6d
8.3
8.6
NS
Primary Outcome
Secondary Outcomes
(Canadian Critical Care Trials Group. NEJM
20063552619-2630)
23
Non-invasive Strategy for Diagnosing HAP/VAP

• Clinical approach
• CPIS clinical pulmonary infection score
• Quantitative prediction model using clinical
  criteria
• May improve clinical diagnosis of HAP
• 72-85 sensitive, 85-91 specific
• Only validated in several small studies

(Pugin J, Auckenthaler R, Mili N, et al. Am Rev
Respir Dis 19911431121-1129) (Hubmayr RD et al
ATS Consensus Statement Intensive Care Med
2002281521-1536)
24
CPIS Used for the Diagnosis of VAP

• Temperature ?C Points
• ? 36.5 and ? 38.4 0
• ? 38.5 and ? 38.9 1
• ? 39.0 or ? 36.0 2
• Blood leukocytes, mm-3
• ? 4,000 and ? 11,000 0
• lt 4,000 or gt 11,000 1
• band forms 500 1
• Tracheal secretions
• Absence of tracheal secretions 0
• Presence of tracheal secretions 1
• Purulent secretions 1

CPIS score gt 6 Sensitivity 93
Specificity 100
(Pugin J et al. Am Rev Respir Dis
19911431121-1129)
25
CPIS Used for the Diagnosis of VAP (contd)

• Oxygenation PaO2/FiO2, mm Hg
• gt 240 or ARDS 0
• ? 240 and no evidence ARDS 2
• Pulmonary radiography
• No infiltrate 0
• Diffuse or patchy infiltrate 1
• Localized infiltrate 2
• Culture of tracheal aspirate (semiquantitative
  0-1-2-3 )
• Pathogenic bacteria cultured ? 1 or no
  growth 0
• Pathogenic bacteria cultured gt 1 1
• Same pathogenic bacteriaon Gram Stain gt 1 1

CPIS score gt 6 Sensitivity 93
Specificity 100
(Pugin J, et al. Am Rev Respir Dis 1991
1431121-1129)
26
Short Course Therapy of Suspected VAP Using the
CPIS

• CPIS on diagnosis with 5 criteria fever, WBC,
  trach secretions, oxygen, X-ray.
• CPIS on day 3 with 7 criteria add x-ray
  progression, culture data.

(Singh N et al. AJRCCM 2000162505-511)
27
Invasive Strategy for Diagnosing HAP

• Quantitative culture approach
• bronchoscopic protected specimen brush (103
  CFU/ml)
• 67 sensitive, 95 specific
• bronchoalveolar lavage (104 CFU/ml)
• 73 sensitive, 82 specific
• quantitative endotracheal aspirate (105 CFU/ml)
• 38-100 sensitive, 14-100 specific
• Antibiotic use more appropriate and accurate
• Claim of improved survival at 28 days

(Fagon JY, Chastre J, Wolff M, et al. Ann Intern
Med 2000132621-630) (Craven DE, and Steger KA,
et al. Infect Cont Hosp Epidemiol
199718783-795) (Grossman RF and Fein A. Chest
2000117177S-181S)
28
Meta-analysis of BronchoscopyMortality
(Shorr Crit Care Med 20053346-53)
29
Figure 1 Diagnostic Algorithm for HAP
Patient on ward
Clinical features suggest infection?
No further investigation/observe
No
Yes
Order/review recent chest roentgenogram
Abnormal ?
Observe Investigate for other sources
No
Yes
30
Figure 1 (contd)Diagnostic Algorithm for HAP
Calculate CPIS
CPIS 6
CPIS gt 6
Consider therapy
No pus cells or organisms
Gram stain tracheobronchial secretions if pus
cells organisms present (Yes)
Recalculate CPIS daily examine Gram stain
Treat according to Gram stain and local
epidemiology
Stop therapy if CPIS ?6 on day 3
31
Figure 2Diagnostic Algorithm for VAP
Mechanically ventilated patient
Clinical features suggest infection?
No further investigation/observe
No
Yes
Order/review recent chest roentgenogram
Abnormal?
Observe Investigate for other sources
Yes
32
Figure 2 (cont)Diagnostic Algorithm for VAP
Calculate CPIS
CPIS 6
CPIS gt 6
CPIS 4
CPIS lt 4
Gram stain tracheobronchial secretions Yes
organisms pus cells present
NO
Consider therapy and no alternate diagnosis
Stop therapy if started
Treat according to Gram stain and local
epidemiology
Recalculate CPIS daily examine Gram stain Stop
therapy after 3 days if CPIS ?6
33
Initial Therapy of HAP/VAP
34
The Importance of Initial Empiric Antibiotic
Selection




p lt.05

(Alvarez-Lerma F. Intensive Care Med
199622387-94) (Rello J, Gallego M, Mariscal D,
et al. Am J Respir Crit Care Med
1997156196-200) (Luna CM, Vujacich P, Niederman
MS et al. Chest 1997111676-685) (Kollef MH and
Ward S. Chest 1998113412-20)
(Clech C, Timsit J-F, De Lassence A et al.
Intensive Care Med 2004301327-1333)
35
Figure 1.Initial Empiric Antibiotic Therapy of
HAP
Diagnosis of HAP
Mild-Moderate Presentation Risk Factors for
Resistance Group 2
Mild-Moderate Presentation Group 1
Severe Presentation Group 3
Treat in ICU with IV Combination Therapy IV
Initially
Treat on Ward with IV/Oral Monotherapy for Core
Pathogens for 7-8 days
Treat on Ward with IV/Oral Monotherapy for Core
Pathogens and Possible Resistant Pathogens for
7-8 days
Streamline Therapy Based on Culture Results
Streamline Therapy Based on Culture Results
Modify Treatment if Resistant Pathogens Present
Resistant Pathogens such as P. aeruginosa,
Acinetobacter spp., S. maltophilia and MRSA may
require longer durations of treatment (14 da)
36
Figure 2.Initial Empiric Antibiotic Therapy of
VAP
Diagnosis of VAP in ICU
Severe Presentation and/or Risk Factors for
Resistance Group 5
Moderate Presentation Group 4
Treat in ICU with Combination Therapy IV
Initially
Treat in ICU with IV Monotherapy for 7-8 Days
Streamline Therapy Based on Culture Results
Streamline Therapy Based on Culture Results
(Monotherapy IV may be appropriate for 7-8 days)
Resistant Pathogens such as P. aeruginosa,
Acinetobacter spp., S. maltophilia and MRSA may
require longer durations of treatment (14 da)
37
HAP Group 1 Mild-Moderate Presentation,
Early Onset (lt 5 days), and No Risk Factors for
Resistance.  
  mild-moderate presentation no hypotension,
intubation, sepsis syndrome, rapid progression of
infiltrates or multiple organ dysfunction.
38
Treatment of HAP Group 1

• No risk factors for resistance mild-moderate
  presentation
• Treatment
• 3rd generation non-pseudomonal cephalosporin
• (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g
  q8h IV)
• or 4th generation cephalosporin (cefepime 1-2g
  q12h IV)
• OR
• beta-lactam/beta-lactamase inhibitor
• (eg. piperacillin-tazobactam 4.5 g q8h IV)
• OR
• fluoroquinolone (levofloxacin 750 mg IV qd or
  moxifloxacin 400 mg IV qd) ? po

39
HAP Group 2- Mild-Moderate Presentation, and
Risk Factors for Resistance (Prior Antimicrobial
Therapy in Preceding 90 days and/or
Hospitalization for gt 5 days).
40
Treatment of HAP Group 2

• Risk factors for resistance, and/or late
  onset mild-moderate presentation (Contd)
• Treatment
• 3rd generation non-pseudomonal cephalosporin
  (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h
  IV) or 4th generation cephalosporin (cefepime 1-2
  g q12h IV)
• OR
• piperacillin-tazobactam 4.5 g q8h IV
• OR
• imipenem 500 mg q6h IV
• OR
• meropenem 500 mg q6h IV
• OR
• levofloxacin 750 mg q24h IV
• OR
• moxifloxacin 400 mg q24h IV
• /-
• vancomycin 1 g q12h IV or linezolid 600 mg q12h
  IV

41
Treatment of HAP Group 2 (contd)

• Risk factors for resistance, and/or late onset (
  5 days) mild-moderate presentation (Contd)
• Treatment (contd)
• For suspected P. aeruginosa
• beta-lactam/beta-lactamase inhibitor
  (piperacillin-tazobactam 4.5 g q6h IV)
• or
• antipseudomonal cephalosporin (ceftazidime or
  cefepime 2 g q8h IV)
• or
• carbapenem (imipenem or meropenem 1 g q8h IV)
• plus
• fluoroquinolone (ciprofloxacin 400 mg q8h IV or
  750 mg BID po or levofloxacin 750 mg q24h IV/po)
• or
• aminoglycoside (gentamicin or tobramycin 5-7
  mg/kg q24h IV or amikacin 15-20 mg/kg q24h IV)

42
HAP Group 3- Severe Presentation, /or Risk
Factors for Resistance (Prior Antimicrobial
Therapy in Preceding 90 days and/or
Hospitalization for gt 5 days)
43
HAP Group 3-Severe Presentation (Hypotension,
Need for Intubation, Sepsis Syndrome, Rapid
Progression of Infiltrates or End Organ
Dysfunction) and/or Risk for Resistance

• Treatment
• Treat with combination therapy
• anti-pseudomonal cephalosporin (ceftazidime
  or cefepime 2 g q8h IV)
• or
• beta-lactam/beta-lactamase inhibitor
  (piperacillin-tazobactam
• 4.5 g q6h IV)
• or
• carbapenem (imipenem or meropenem 1g q8h IV
  or 1 g q8h IV)
• plus
• fluoroquinolone (ciprofloxacin 400 mg q8h
  IV or levofloxacin 750 mg q24h IV)
• or
• aminoglycoside (gentamicin or tobramycin
  5-7mg/kg qd IV or amikacin 15-20 mg/kg qd IV)
• /-
• vancomycin 1 g q12 h IV or linezolid 600 mg
  q12 h IV if MRSA present or suspected

44
VAP Group 4-Moderate Presentation, No Risk
Factors for Resistance and Early Onset lt 5 days.
45
Treatment of VAP Group 4

• No risk factors for resistance, early onset (lt5
  days of hospitalization) moderate presentation
• Treatment
• 3rd generation non-pseudomonal cephalosporin
• (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g
  q8h IV)
• or 4th generation cephalosporin (cefepime 2 g
  q12h IV)
• OR
• beta-lactam/beta-lactamase inhibitor
• (eg. piperacillin-tazobactam 4.5 g q6h IV)
• OR
• fluoroquinolone (levofloxacin 750 mg IV qd,
  moxifloxacin 400 mg IV qd ? po

46
Therapy of VAP Group 5

• Group 5 Risk factors for antimicrobial resistance
  present, late onset and/or severe presentation

Risk factors for antimicrobial resistance
present - Prolonged hospitalization -
Prior hospital antimicrobial
therapy within 90 d - ICU stay ? 5 days
- Structural lung disease - P. aeruginosa or
Acinetobacter spp. Severe
presentation - hypotension, intubation, severe
sepsis, rapid progression of infiltrates or organ
dysfunction
47
VAP Group 5-Severe Presentation, Risk Factors
for Antimicrobial Resistance, and/or Late Onset gt
5 Days
48
Treatment of VAP Group 5

• Risk factors for resistance present /- severe
  presentation (Contd)
• Treatment
• ceftazidime 2 g q8h IV or cefepime 2g q8h
  IV
• OR
• imipenem-cilastatin 1 g q8h
  IV
• OR
• meropenem 1 g q8h IV
• OR
• piperacillin-tazobactam 4.5 g q6h IV
• PLUS
• ciprofloxacin 400 mg q8h IV or levofloxacin
  750 mg q24h IV
• OR
• gentamicin or tobramycin 5-7 mg/kg q24h IV
  or amikacin 15-20 mg/kg q24h IV
• /-
• vancomycin 1 g q12h IV or linezolid 600 mg
  q12h IV

49
Short Course Therapy of Suspected VAP Using the
CPIS

• CPIS on diagnosis with 5 criteria fever, WBC,
  trach secretions, oxygen, X-ray.
• CPIS on day 3 with 7 criteria add x-ray
  progression, culture data.

(Singh N et al. AJRCCM 2000162505-511)
50
VAP 8 Day vs. 15 Day Antibiotic Therapy
Shorter may be Better
76.2
57.1
or Days
40.6
P.01
28.9
26
28.9
18.4 d
18.8
17.2
15.3 d
Primary Outcomes
(Chastre J et al. JAMA 20032902588-2598)
51
Summary

• Clinical diagnostic criteria more adaptable to
  the Canadian clinical environment.
• Appropriateness of therapy important in treatment
  of HAP.
• In VAP, appropriateness and early initiation of
  antimicrobial therapy particularly important.
• Severity of illness and risk for resistance
  determine initial antimicrobial selection.
• 7 or 8 days of therapy may suffice for most cases
  of HAP VAP but 14 days preferred for P.
  aeruginosa Acinetobacter spp.