' ' ARMAGANIDIS Professor of Pulmonary and Critical Care Medicine Medical School of Athens Universit

1
?. ?. ARMAGANIDIS Professor of Pulmonary and
Critical Care MedicineMedical School of Athens
University Head of the 2nd Critical Care
Department ??????? University HospitalAthens -
Greece
PNEUMONIA in the ICU
2
Disclosure Information

• Prof. A. E. Armaganidis, MD
• I have no potential conflict of interest with the
  topic that I am going to discuss

3
PNEUMONIA in the ICUTopics

• Terminology of PNEUMONIA
• in the ICU mainly VAP (and HAP)
• Definition and Epidemiology
• Pathogenesis
• Prevention
• Diagnosis
• Treatment (Etiology ?)
• New developments

4
PNEUMONIA in the ICU Terminology of PNEUMONIA
Anand N, Kollef MH The alphabet soup of
pneumonia CAP, HAP, HCAP, NHAP and VAP Semin
Respir Crit Care Med 2009

• C Community
• H Hospital
• HC Health Care
• NH Nursing Home
• V Ventilator

Acquired Pneumonia
5
PNEUMONIA in the ICU Terminology of PNEUMONIA

• Which is the purpose of this categorization?
• To have a better epidemiological description of
  the disease
• To classify patients according the severity of
  disease and expected outcome
• To define groups of patients with different
  characteristics and immune status
• To define groups of patients differing mainly in
  the appropriate empirical treatment

6
PNEUMONIA in the ICU Terminology of PNEUMONIA

• Which is the purpose of this categorization?
• To have a better epidemiological description of
  the disease
• To classify patients according the severity of
  disease and expected outcome
• To define groups of patients with different
  characteristics and immune status
• To define groups of patients differing mainly in
  the appropriate empirical treatment

7
Which of the following is true about VAP
epidemiology (I)

• The term VAP refers to pneumonia cases observed
  in all ICU patients
• VAP occurs also in ICU patients under non
  invasive mechanical ventilation
• The term VAP refers to pneumonia observed gt5 days
  in intubated pts only
• Most cases of VAP occur in the first week after
  intubation

8
Which of the following is true about VAP
epidemiology (II)

• VAP is a subgroup of HAP with the same
  responsible pathogens in both entities
• The risk to develop VAP increases with time
  during ICU stay
• The risk to develop VAP from MDR pathogens
  increases with time during ICU stay
• There is no effect of time in the etiology of VAP
  during the first 10 days of ICU stay

9
PNEUMONIA in the ICU VAP definition and
epidemiology (I)
VAP

• VAP refers to pneumonia that arises gt 48 h after
  endotracheal intubation among patients treated in
  an ICU setting
• Early-onset (lt5 days) vs Late-onset pneumonia
• VAP occurs in 9-27 of all intubated patients,
  Risk 3/d the first 5 days, 2/d D5 to D10,
  1/d after D10 (6 to 20-fold increase of HAP with
  MV but not with NIPPV)
• VAP attributable mortality 33-50 (HAP 30-70)

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Crit Care Med 2009
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PNEUMONIA in the ICU VAP definition and
epidemiology (II)
H AP

• VAP is a subgroup of HAP (mixed publications)
• HAP 2nd most common nosocomial infection
• in USA 5-10 cases of 1000 hospital admissions
• Hospital length of stay 7-9 days more
• Estimated cost gt 40 000 / pt
• 25 of ICU infections and gt50 of AB used
• in Canada (2008) 10 cases of 1000 ventilator days
• LOS 4,3 days more, attributable mortality 6,
  4000 cases with a cost of 40 million per year

12
PNEUMONIA in the ICU VAP pathogenesis

• Colonization contributes to pathogenesis
  (importance of factors related to differences in
  colonization)
• Aspiration of oropharyngeal pathogens
• Leakage of secretions around the endotracheal
  tube
• Direct inoculation of pathogens into the lower
  respiratory tract
• Hematogenous spread (IV catheters or )
• Translocation from the GI tract
• Infected biofilm in the ET tube and embolization
• Stomach and sinuses as potential reservoirs (?)

NIPPV Relative Risk for VAP is 0.59 (p 0.015)
13
Which of the following is true about VAP
epidemiology (I)

• The term VAP refers to pneumonia cases observed
  in all ICU patients
• VAP occurs also in ICU patients under non
  invasive mechanical ventilation
• The term VAP refers to pneumonia observed gt5 days
  in intubated pts only
• Most cases of VAP occur in the first week after
  intubation

14
Which of the following is true about VAP
epidemiology (I)

• The term VAP refers to pneumonia cases observed
  in all ICU patients
• VAP occurs also in ICU patients under non
  invasive mechanical ventilation
• The term VAP refers to pneumonia observed gt5 days
  in intubated pts only
• Most cases of VAP occur in the first week after
  intubation

15
Which of the following is true about VAP
epidemiology (II)

• VAP is a subgroup of HAP with the same
  responsible pathogens in both entities
• The risk to develop VAP increases with time
  during ICU stay
• The risk to develop VAP from MDR pathogens
  increases with time during ICU stay
• There is no effect of time in the etiology of VAP
  during the first 10 days of ICU stay

16
Which of the following is true about VAP
epidemiology (II)

• VAP is a subgroup of HAP with the same
  responsible pathogens in both entities
• The risk to develop VAP increases with time
  during ICU stay
• The risk to develop VAP from MDR pathogens
  increases with time during ICU stay
• There is no effect of time in the etiology of VAP
  during the first 10 days of ICU stay

17
Which of the following is true about VAP
prevention (I)

• Prophylactic use of appropriate antibiotics is
  indicated
• Closed suction systems decrease VAP incidence
• Subglotic secretions suction prevents early but
  not late-onset VAP
• Polyurethane cuffs prevent early but not
  late-onset VAP

18
Which of the following is true about VAP
prevention (I)

• An increase of nursing staff by 15
• can reduce the risk for all acquired ICU
  infections by 30
• can decrease the risk of VAP by 15
• can decrease the risk of VAP by 50

19
PNEUMONIA in the ICU VAP prevention (I)

• Important impact on the mortality and morbidity
  gt prevention gtgtgt treatment
• Pharmacological non-pharmacological measures
  (better term airway care measures)
• HME vs. active humidifiers
• Open vs. closed tracheal suction system
• Subglottic secretions suction and ET cuff
• and

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PNEUMONIA in the ICU VAP prevention (II)

• HME vs. humidifiers Lorente et al 2006, Siempos
  et al 2008
• Wide acceptance, no consensus, no effect on
  incidence, mortality, length of ICU stay,
  duration of MV, episodes of airway obstruction
  (gt ?)
• Open vs closed tracheal suction system Cochrane
  database 2007, Siempos et al 2008
• incidence, mortality, LOS ? derecruitment,
  incidence of MDR pathogens protection ???
• Subglottic secretions suction and new ET cuff
  Valles 1995, Dezfulian 2005, Lorente 2007
• incidence 22gt8, early and late onset VAP

21
PNEUMONIA in the ICU VAP prevention (III)

• The use of Bundles (Sepsis Bundle, VAP
  prevention Bundle, Ventilator Bundle 4 items)
• hand hygiene and staff education but also
• semi-recumbent position
• oropharyngeal decontamination
• control of endotracheal cuff pressure
• limited change of ventilator circuits
• microbiological surveillance
• standardized protocols for sedation and weaning
• antibiotic control policies AND
• nurse/patient staffing ratios

22
Which of the following is true about VAP
prevention (I)

• An increase of nursing staff by 15
• (improved nursepatient ratio from 1,9 to 2,2)
• can reduce the risk for all acquired ICU
  infections by 30
• can decrease the risk of VAP by 15
• can decrease the risk of VAP by 50

23
Which of the following is true about VAP
prevention (I)

• An increase of nursing staff by 15
• (improved nursepatient ratio from 1,9 to 2,2)
• can reduce the risk for all acquired ICU
  infections by 30
• can decrease the risk of VAP by 15
• can decrease the risk of VAP by 50

24
Which of the following is true about VAP
prevention (I)

• An increase of nursing staff by 15
• (improved nursepatient ratio from 1,9 to 2,2)
• can reduce the risk for all acquired ICU
  infections by 30
• can decrease the risk of VAP by 15
• can decrease the risk of VAP by 50 (hazard ratio
  0,42)

Gastmeier and al 2007 31-57 VAP reduction with
multi-module programmes
25
Which of the following is true about VAP
prevention (I)

• Prophylactic use of appropriate antibiotics is
  indicated
• Closed suction systems decrease VAP incidence
• Subglotic secretions suction prevents early but
  not late-onset VAP
• Polyurethane cuffs prevent early but not
  late-onset VAP

26
Which of the following is true about VAP
prevention
bundle ?

• Prophylactic use of appropriate antibiotics is
  effective
• Closed suction systems decrease VAP incidence
• Subglotic secretions suction prevents early but
  not late-onset VAP
• Polyurethane cuffs prevent early but not
  late-onset VAP

27
Which of the following is true about VAP
diagnosis

• VAP is more often a clinical diagnosis
• VAP must be a microbiological diagnosis
• VAP can be confirmed by the CPI Score
• Diagnosis of VAP can really be confirmed only
  using biopsy specimens culture

28
Which of the following is true about VAP
diagnosis

• For the diagnosis of VAP it better to use
• Bronchoscopic samples rather than cultures of
  blind non bronchoscopic samples
• Quantitative rather than qualitative cultures of
  tracheal secretions
• Protected brush samples rather than non protected
  BAL cultures
• None of the diagnostic tests can confirm the
  presence of VAP

29
PNEUMONIA in the ICU VAP diagnosis

• At least 2 of the following 3 clinical findings
• fever leukocytosis purulent secretions
• usually with abnormal findings on chest
  radiographic studies but
• The usual problem in clinical practice
  sensitivityspecificity gt scores like CPIS
• All 4 present sensitivity lt50
• The best new progressive infiltrate 2 out of
  3 clinical features
• Association with microbiological data

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CPIS
Temperature 3 points
Blood leucocytes 2 points
Tracheal secretions 2 points
Oxygenation 2 points
Pulmonary radiography 2 points
Progression of pulm. infiltrate 2 points
Culture of aspirate 3 points
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PNEUMONIA in the ICU VAP diagnosis

• CPIS gt 6 gt a good correlation with
• () non bronchoscopic BAL cultures
• Pugin et al 1991, Singh et al 2000
• These findings were not confirmed by others
• but accuracy improves if a () Gram stain
• is added to the evaluation
• Fabregas et al 1999, Fartoukh et al 2003

32
PNEUMONIA in the ICU VAP diagnosis

• Clinical manifestations radiological findings
  initial screening for VAP
• Blood cultures (extra-pulmonary infection ?)
• Samples of lower respiratory tract secretions
  thoracentesis before AB use or change (72 hrs)
• Cultures of lower respiratory tract secretions
• qualitative vs. quantitative cultures
• simple or protected endotracheal aspirate or BAL
  (non bronchoscopic)
• bronchoscopic samples BAL, protected brush

33
PNEUMONIA in the ICU VAP diagnosis

• Re-evaluation by day 3 is appropriate
• (CPIS lt 6 for 3 days stop AB Singh et al 2000 )
• qualitative vs. quantitative cultures ???
• simple or protected endotracheal aspirate or BAL
• and bronchoscopic samples (BAL, protected brush)
• no difference in mortality (no superiority) but
  a bronchoscopic strategy decreased mortality in
  a large study Fagon et al 2000
• Canadian Trial NEJM 2006 no difference in
  mortality, days without AB, LOS, MODS
• The old story of sensitivity specificity for a
  purpose

34
PNEUMONIA in the ICU VAP diagnosis

• The old story of sensitivity specificity for a
  purpose
• High sensitivity and low specificity AB overuse
• Fagon et al 2000, Sanchez et al 1998, Ruiz et al
  2000, Sole Violan et al 2000
• Delays in initiation of appropriate AB treatment
  increases VAP mortality gt treat without waiting
  for diagnostic tests in severe pts
• El Ebiary et al 1997, Kollef et al 1999, Luna et
  al 2006
• In the absence of a perfect diagnostic test
• Start treatment as soon as possible (specimens)
  De-escalation based on results reevaluation
• Selection of tests based on the purpose ???

35
PNEUMONIA in the ICU VAP diagnostic strategy and
outcome

• It is mainly a strategy including a diagnostic
  procedure that could improve outcome
• Decrease of 14-day mortality (not 28-day
  mortality) in one large study only (Fagon et al
  2000)
• No effect in the larger Canadian study NEJM 2006
• No superiority of oriented vs. blind and
  qualitative vs. quantitative cultures
• But exclusion criteria
• Usefulness of tests for a purpose and group of
  pts under specific circumstances EBM but
  complete absence of medicine based evidence

36
Which of the following is true about VAP
diagnosis

• VAP is more often a clinical diagnosis
• VAP must be a microbiological diagnosis
• VAP can be confirmed by the CPI Score
• Diagnosis of VAP can really be confirmed only
  using biopsy specimens

37
Which of the following is true about VAP
diagnosis

• VAP is more often a clinical diagnosis
• VAP must be a microbiological diagnosis
• VAP can be confirmed by the CPI Score
• Diagnosis of VAP can really be confirmed only
  using biopsy specimens

38
Which of the following is true about VAP
diagnosis

• For the diagnosis of VAP it better to use
• Bronchoscopic samples rather than cultures of
  blind non bronchoscopic samples
• Quantitative rather than qualitative cultures of
  tracheal secretions
• Protected brush samples rather than non protected
  BAL cultures
• None of the diagnostic tests can confirm the
  presence of VAP

39
Which of the following is true about VAP
diagnosis

• For the diagnosis of VAP it better to use
• Bronchoscopic samples rather than cultures of
  blind non bronchoscopic samples
• Quantitative rather than qualitative cultures of
  tracheal secretions
• Protected brush samples rather than non protected
  BAL cultures
• None of the diagnostic tests can confirm the
  presence of VAP (all provide a probability of VAP)

40
Which of the following is true about VAP
treatment

• Empiric treatment must be based on
• International guidelines
• Local microbiological data
• Epidemiological data related to patients history
  and previous hospitalizations
• Previously used antibiotics

41
Which of the following is true about VAP
treatment

• Basic principles to select empiric treatment are
• Assure maximum efficacy by giving early,
  appropriate and effective antibiotherapy
• Delay treatment until the performance of
  diagnostic tests to improve specificity
• Decrease abuse of AB by de-escalation and
  decrease tt duration to 7 days

42
PNEUMONIA in the ICU VAP treatment

• Empiric therapy Risk of MDR pathogens ??
  (Terminology AND etiology of pneumonia)
• Risk factors (ATS IDSA)
• Hospitalization gt 5 days
• Admission from health-care-related facility
• Recent prolonged antibiotic therapy
• Choice of AB local microbiology (and case mix)
  availability and cost, previous antibiotic tt,
  restrictions ? Combination AB therapy ?

43
HCAP includes any patient who

• was hospitalized in an acute care hospital for
  two or more days within the past 90 days
• resided in a nursing home or long-term care
  facility
• received recent intravenous antibiotic therapy,
  chemotherapy, or wound care within the past 30
  days
• attended a hospital or hemodialysis clinic

44
Other risk factors for MDR pathogens (HCAP risk
factors)

• Antimicrobial therapy in preceding 90 d
• Current hospitalization of 5 d or more
• High frequency of antibiotic resistance
• in the community or
• in the specific hospital unit
• Immunosupressive disease or therapy

45
PNEUMONIA in the ICU VAP treatment

• Basic principle ensure maximum efficacy
• early appropriate AB in adequate doses
• avoid abuse of AB by de-escalation
• Combination AB therapy ?
• larger spectrum for MDR pathogens
• monotherapy in their absence de-escalation
• Duration of treatment can be shortened from
  traditional 14-21 days to periods as little as 7
  days
• (provided that it is not a Pseudomonas
  aeroginosa and that the patient has a good
  clinical response !!!)

46
PNEUMONIA in the ICUVAP treatment response to
therapy ?
Biomarkers ?

• Serial assessment of clinical parameters
• Reevaluation results of cultures 48-72 hrs
• Good OR no response after 3 days of tt
• De-escalation of AB, narrowing therapy ?
• Complications of pneumonia OR therapy,
  unsuspected or MDR pathogens, extra-pulmonary
  sites of infection mimics of pneumonia by
  noninfectious disease gt
• Re-evaluation with additional tests

47
PNEUMONIA in the ICU VAP treatment - etiology

• MDRs Pseudomonas, Acinetobacter, Klebsiella
• combination therapy ? Local resistance
• carbapenems (?), sulbactam, colistin
• avoid cephalosporins if extended-spectrum
  b-lactamase-positive Enterobacteriacea, avoid
  carbapenems if MBL with high MIC
• MRSA Linezolid gt Vancomycin (local data)

48
Which of the following is true about VAP
treatment

• Empiric treatment must be based on
• International guidelines
• Local microbiological data
• Epidemiological data related to patients history
  and previous hospitalizations
• Previously used antibiotics

49
Which of the following is true about VAP
treatment

• Empiric treatment must be based on
• International guidelines
• Local microbiological data
• Epidemiological data related to patients history
  and previous hospitalizations
• Previously used antibiotics

50
Which of the following is true about VAP
treatment

• Basic principles to select empiric treatment are
• Assure maximum efficacy by giving early,
  appropriate and effective antibiotherapy
• Delay treatment until the performance of
  diagnostic tests to improve specificity
• Decrease abuse of AB by de-escalation and
  decrease tt duration to 7 days

51
Which of the following is true about VAP
treatment

• Basic principles to select empiric treatment are
• Assure maximum efficacy by giving early,
  appropriate and effective antibiotherapy
• Delay treatment until the performance of
  diagnostic tests to improve specificity
• Decrease abuse of AB by de-escalation and
  decrease tt duration to 7 days

52
Which of the following is true about new
developments related to VAP

• Surveillance cultures of tracheal secretions are
  very useful to define empiric treatment of VAP
• Following traditional guidelines we can define
  appropriate AB treatment for VAP with great
  accuracy
• New types of ET tubes can decrease the incidence
  of VAP

53
PNEUMONIA in the ICU New developments (I)

• Surveillance cultures and Empiric treatment
• adequate in 38 of 40 pts (95) Michel et al 2005
  but if traditional guidelines were followed
  (Troulliet et al 1998, ATS 2005) adequate tt in
  68
• Papadomichelakis et al 2008 Concordance 82,
  knowledge of colonization improved the rate of
  adequate empiric antimicrobial treatment (91 vs.
  40 in VAP and 86 vs. 50 in BSI cases, Plt0.05)
• Jung et al 2009 similar results once-a-week
  cultures, adequate in 85,vs. 73 guidelines,
  61 no data

54
PNEUMONIA in the ICU New developments (II)
bundles ?

• New ET tubes (like protected KTs)
• Biofilm formation is a risk factor
• Coating the ET tube with silver
• Kollef et al 2008 2003pts, multicenter,
  prospective, randomized, single blind, controlled
  trial)
• VAP in 4,8 vs. 7,5 (p 0.03)
• risk reduction absolute2,7 - relative36
• Delayed occurrence of VAP (p 0.005)
• No difference in mortality, LOS, adverse effects,
  duration of intubation

55
Which of the following is true about new
developments related to VAP

• Surveillance cultures of tracheal secretions are
  very useful to define empiric treatment of VAP
• Following traditional guidelines we can define
  appropriate AB treatment for VAP with great
  accuracy
• New types of ET tubes can decrease the incidence
  of VAP

56
Which of the following is NOT true about new
developments related to VAP

• Surveillance cultures of tracheal secretions are
  very useful to define empiric treatment of VAP
• Following traditional guidelines we can define
  appropriate AB treatment for VAP with great
  accuracy
• New types of ET tubes can decrease the incidence
  of VAP

57
Which of the following is NOT true about new
developments related to VAP

• Surveillance cultures of tracheal secretions are
  very useful to define empiric treatment of VAP
• Following traditional guidelines we can define
  appropriate AB treatment for VAP with great
  accuracy
• New types of ET tubes can decrease the incidence
  of VAP

58
Evidence Based Medicine for clinical practice
guidelines There is a long way from RCTs to
the individual patient
VASOPRESSIN
PROTEIN C
IV?G
CORTICOSTEROIDS
ANTIBIOTICS
Further research is required because
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(No Transcript)
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Critical Care Med 2006, 342, 344-353
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PNEUMONIA in the ICU References and recommended
reading

• From Procite 4