Ventilator Associated Pneumonia in ICU.ppt

pneumonia

1. Tracking NI has become
difficult
Shorter inpatient stays (average
postoperative stay, now
approximately 5 days, is usually
shorter than the 5-to 7-day
incubation period for S. aureus
surgical wound infections)
Surveillance systems are optional to
hospitals with infection-control
programs

2. Prevention of
Ventilator
Associated
Pneumonia
(VAP)
AACN VAP Practice Alert

3. Lecture Content
Epidemiology of
VAP
Prevention
strategies
HOB elevation
Ventilator
equipment changes
Continuous removal
of subglottic
secretions
Handwashing
AACN VAP Practice Alert

4. Epidemiology of Ventilator Associated
Pneumonia (VAP)
AACN VAP Practice Alert

5. Nosocomial Pneumonias
Account for 15% of all hospital
associated infections
Account for 27% of all MICU
acquired infections
Primary risk factor is mechanical
ventilation (risk 6 to 21 times the
rate for nonventilated patients)
CDC Guideline for Prevention of Healthcare Associated
Pneumonias 2003
Cook et al, Ann Intern Med 1998;129:433
AACN VAP Practice Alert

6. Critical Care Interventions Increase Susceptibility
to Nosocomial Pneumonias
Tracheal
Colonization
Altered
Host
Defenses
Increased
Nosocomial
Pneumonias
Intubation
AACN VAP Practice Alert

7. VAP Etiology
Most are bacterial pathogens, with
Gram negative bacilli common:
Pseudomonas aeruginosa
Proteus spp
Acinetobacter spp
Staphlococcus aureus
Early VAP associated with non-multi-
antibiotic-resistant organisms
Late VAP associated with antibiotic-
resistant organism
AACN VAP Practice Alert

9. Significance of Nosocomial
Pneumonias
Mortality ranges from 20 to 41%,
depending on infecting organism,
antecedent antimicrobial therapy, and
underlying disease(s)
Leading cause of mortality from
nosocomial infections in hospitals
CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003
Heyland et al, Am J Respir Crit Care Med 1999;159:1249
Bercault et al, Crit Care Med 2001;29:2303
AACN VAP Practice Alert

10. Significance of Nosocomial
Pneumonias
Increases ventilatory support
requirements and ICU stay by 4.3
days
Increases hospital LOS by 4 to 9
days
Increases cost -
Heyland et al, Am J Respir Crit Care Med
1999;159:1249
Craven D. Chest 2000;117:186-187S
Rello et al, Chest 2002;122:2115
AACN VAP Practice Alert

11. VAP Prevention
AACN VAP Practice Alert

12. Continuous Removal of
Subglottic Secretions
Use an ET tube with
continuous suction
through a dorsal lumen
above the cuff to
prevent drainage
accumulation
CDC Guideline for Prevention of Healthcare Associated Pneumonias
2003
Kollef et al, Chest 1999;116;1339
AACN VAP Practice Alert

13. HOB Elevation
HOB at 30-45
o
CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003
Drakulovic et al, Lancet 1999;354:1851

14. Frequency of Equipment
Changes
Ventilator
Tubing
Inner
Cannulas
of Trachs
Ambu
Bags
No Routine
Changes
Not Enough
Data
Between
Patients
CDC Guideline for
Prevention of Healthcare Associated Pneumonias
2003
AACN VAP Practice Alert

15. Handwashing
What role does handwashing play in
nosocomial pneumonias?
Albert, NEJM 1981; Preston, AJM 1981; Tablan, 1994AACN VAP Practice Alert

16. VAP Prevention
All recommendations are level IA
CDC Guideline for Prevention of Healthcare Associated
Pneumonias 2003
AACN Practice Alert for VAP, 2004
Wash hands before and
after suctioning, touching
ventilator equipment,
and/or coming into
contact with respiratory
secretions.
AACN VAP Practice Alert

17. Use a continuous subglottic
suction ET tube for intubations
expected to be > 24 hours
Keep the HOB elevated to at
least 30 degrees unless
medically contraindicated
VAP Prevention
All recommendations are level II
CDC Guideline for
Prevention of Healthcare Associated Pneumonias
2003
AACN Practice Alert for VAP, 2004
AACN VAP Practice Alert

18. No Data to Support These
Strategies
Use of small bore versus large bore
gastric tubes
Continuous versus bolus feeding
Gastric versus small intestine tubes
Closed versus open suctioning
methods
Kinetic beds
CDC Guideline for
Prevention of Healthcare Associated
Pneumonias 2003
AACN VAP Practice Alert

19. Potential consequences of
inappropriate antibiotic therapy
Inappropriate empiric antibiotic
therapy can lead to increases in:
mortality
morbidity
length of hospital stay
cost burden
resistance selection

20. Inappropriate antibiotic
therapy
Inappropriate antibiotic therapy can
be defined as one or more of the
following:
ineffective empiric treatment of
bacterial infection
at the time of its identification
the wrong choice, dose or duration of
therapy
use of an antibiotic to which the
pathogen
is resistant

21. Evidence of improved clinical
outcomes with appropriate
empiric antibiotic therapy
A number of studies have
demonstrated the
benefits of early use of
appropriate empiric
antibiotic therapy for patients
with nosocomial infections
Several key clinical studies are
reviewed in the following
slides

22. Inappropriate antibiotic therapy is a risk
factor for mortality among patients in the
intensive care unit (ICU)
Infection-related mortality rates were assessed
in a prospective cohort, single-centre study of
2000 patients admitted to medical/surgical ICUs
655 patients had a clinically recognised
infection:
442 (67.5%) had a community -acquired
infection
286 (43.7%) developed a nosocomial
infection
73 (11.1%) had both community -acquired
and nosocomial infections
169 (25.8%) patients received inappropriate
initial antimicrobial treatment
Kollef et al. Chest 1999;115:462–474

23. Inappropriate antibiotic therapy is
a risk factor for mortality among
patients in the ICU
Kollef et al. Chest 1999;115:462–474
Hospital mortality (%)
0
20
50
60
Appropriate therapyInappropriate therapy
40
30
10
All causes Infectious disease-related
p<0.001
p<0.001
Mortality type

24. Appropriate antibiotic therapy reduces
mortality and complications in patients
with nosocomial pneumonia
The frequency of and reasons for changing empiric
antibiotics during the treatment of hospital-acquired
pneumonia were assessed in a prospective
multicentre study across
30 Spanish hospitals
Of the 16 872 patients initially enrolled, 530
developed
565 episodes of pneumonia after ICU admission
Empiric antibiotics (administered in 490 [86.7%] of
episodes) were modified in 214 (43.7%) cases
because of:
isolation of micro-organism not covered by treatment
(62.1%)
lack of clinical response (36.0%)
development of resistance (6.6%)
Alvarez-Lerma et al. Intensive Care Med 1996;22:387–394

25. Alvarez-Lerma et al. Intensive Care Med 1996;22:387–394
Appropriate antibiotic therapy reduces
mortality and complications in patients
with nosocomial pneumonia
Appropriate
therapy
(n=284)
Attributable mortality
No. complications/patient
Shock
Gastrointestinal bleeding
Respiratory failure
Multiple organ failure
Extrapulmonary infection
Inappropriate
therapy
(n=146) p-value
16.2%
1.73 ±1.82
17.1%
10.7%
24.9%
12.5%
13.2%
24.7%
2.25 ±1.98
28.8%
21.2%
32.2%
21.2%
17.1%
0.04
<0.001
<0.005
0.003
NS
NS
NS

26. Appropriate early antibiotic therapy reduces
mortality rates in patients with suspected
ventilator-associated pneumonia (VAP) (Study
1)
A prospective observation and bronchoscopy study
of patients with VAP assessed the impact of
bronchoalveolar lavage (BAL) data on the selection
of antibiotics and clinical outcomes in a
medical/surgical ICU
132 mechanically ventilated patients (hospitalised
>72 hours) with clinically confirmed VAP underwent
BAL within 24 hours of diagnosis
107 patients received antibiotics prior to
bronchoscopy
25 patients received antibiotics immediately after
bronchoscopy
Mortality rates were assessed in relation to the
adequacy and time of initiation of antibiotic therapy
Luna et al. Chest 1997;111:676–685

27. Luna et al. Chest 1997;111:676–685
Appropriate early antibiotic therapy reduces
mortality rates in patients with suspected
VAP
(Study 1)
Mortality (%)
Pre-BAL Post-BAL Post-culture
result
0
60
100
20
40
80
p<0.001
Appropriate antibiotic
No antibiotic
Inappropriate antibiotic

28. Appropriate early antibiotic therapy reduces
mortality rates and length of hospital stay in
patients with bloodstream infection (Study
1)
An observational prospective cohort study of patients
with bloodstream infection examined whether
appropriate antibiotic therapy improved survival rate
Of the 3413 evaluable patients, 2158 (63%) received
early appropriate antibiotics
defined as starting within 2 days of the first
positive blood culture, and if the causative
pathogen was susceptible
in vitroto the administered drug
Mortality rates and median duration of hospital stay
for surviving patients were determined
Leibovici et al. J Intern Med 1998;244:379–386

29. Appropriate early antibiotic therapy reduces
mortality rates and length of hospital stay in
patients with bloodstream infection (Study 1)
Leibovici et al. J Intern Med 1998;244:379–386
Appropriate
therapy
(n=2158)
Mortality rate
Median duration of
hospital stay
Inappropriate
therapy
(n=1255)p-value
20.2%
9 days
(range 0–117)
34.4%
11 days
(range 0–209)
0.0001
0.0001

30. Summary
Clinical evidence suggests that
early use of appropriate empiric
antibiotic therapy improves
patient outcomes in terms of:
reduced mortality
reduced morbidity
reduced duration of hospital stay

31. Resistance to antibacterial
agents
Antibiotic resistance either arises as a result
of innate consequences or is acquired from
other sources
Bacteria acquire resistance by:
mutation: spontaneous single or multiple
changes in bacterial DNA
addition of new DNA: usually via plasmids,
which can transfer genes from one
bacterium to another
transposons: short, specialised sequences
of DNA that can insert into plasmids or
bacterial chromosomes

32. Mechanisms of antibacterial
resistance (1)
Structurally modified antibiotic
target site, resulting in:
reduced antibiotic binding
formation of a new metabolic
pathway preventing metabolism of
the antibiotic

33. Structurally modified antibiotic
target site
Interior of organism
Cell wall
Target siteBinding
Antibiotic
Antibiotics normally bind to specific binding
proteins on the bacterial cell surface

34. Structurally modified antibiotic
target site
Interior of organism
Cell wall
Modified target site
Antibiotic
Changed site: blocked binding
Antibiotics are no longer able to bind to modified
binding proteins on the bacterial cell surface

35. Mechanisms of antibacterial
resistance (2)
Altered uptake of antibiotics,
resulting in:
decreased permeability
increased efflux

36. Altered uptake of antibiotics:
decreased permeability
Interior of organism
Cell wall
Porin channel
into organism
Antibiotic
Antibiotics normally enter bacterial cells via
porin channels in the cell wall

37. Altered uptake of antibiotics:
decreased permeability
Interior of organism
Cell wall
New porin channel
into organism
Antibiotic
New porin channels in the bacterial cell wall do
not allow antibiotics to enter the cells

38. Altered uptake of antibiotics:
increased efflux
Interior of organism
Cell wall
Porin channel
through cell wall
Antibiotic
Entering Entering
Antibiotics enter bacterial cells via porin
channels in the cell wall

39. Altered uptake of antibiotics:
increased efflux
Interior of organism
Cell wall
Porin channel
through cell wall
Antibiotic
Entering Exiting
Active pump
Once antibiotics enter bacterial cells, they are
immediately excluded from the cells
via active pumps

40. Mechanisms of antibacterial
resistance (3)
Antibiotic inactivation
bacteria acquire genes encoding
enzymes that inactivate antibiotics
Examples include:
-lactamases
aminoglycoside-modifying enzymes
chloramphenicol acetyl transferase

41. Antibiotic inactivation
Interior of organism
Cell wall
Antibiotic
Target siteBinding
Enzyme
Inactivating enzymes target antibiotics

42. Antibiotic inactivation
Interior of organism
Cell wall
Antibiotic
Target siteBinding
Enzyme
Enzyme
binding
Enzymes bind to antibiotic molecules

43. Antibiotic inactivation
Interior of organism
Cell wall
Antibiotic
Target site
Enzyme
Antibiotic
destroyed
Antibiotic altered,
binding prevented
Enzymes destroy antibiotics or prevent binding to target sites

44. Many pathogens possess multiple
mechanisms of antibacterial
resistance
+–Quinolones
–++Trimethoprim
–++Sulphonamide
++Macrolide
+–Chloramphenicol
+–Tetracycline
+++–Aminoglycoside
+Glycopeptide
++++-lactam
Modified targetAltered uptakeDrug inactivation

45. Focus on -lactamantibiotic
resistance mechanisms
Three mechanisms of -lactam
antibiotic resistance are
recognised:
reduced permeability
inactivation with -lactamase
enzymes
altered penicillin-binding proteins
(PBPs)

46. Multiple antibiotic resistance
mechanisms: the -lactams

47. -lactam antibiotic
resistance
AmpC and extended-spectrum -
lactamase (ESBL) production are the
most important mechanisms of -
lactam resistance in nosocomial
infections
The antimicrobial and clinical
features of these resistance
mechanisms are highlighted in the
following slides

48. -lactam resistance:
AmpC -lactamase production
Worldwide problem:
incidence increased from 17−23% between
1991 and 2001 in UK
Very common in Gram-negative bacilli
AmpC gene is usually sited on
chromosomes, but can be present on
plasmids
Enzyme production is either constitutive
(occurring all the time) or inducible (only
occurring in the presence of the
antibiotic)
Pfaller et al. Int J Antimicrob Agents 2002;19:383–388
Sader et al. Braz J Infect Dis 1999;3:97–110; Livermore et al. Int J Antimicrob Agents 2003;22:14−27

49. -lactam resistance: ESBL
production
An increasing global problem
Found in a small, expanding group of
Gram-negative bacilli, most commonly
the Enterobacteriaceaespp.
Usually associated with large plasmids
Enzymes are commonly mutants of TEM -
and
SHV-type -lactamases
Jones et al. Int J Antimicrob Agents 2002;20:426–431
Sader et al. Diagn Microbiol Infect Dis 2002;44:273–280

50. Antimicrobial features of
ESBLs
Inhibited by -lactamase inhibitors
Usually confer resistance to:
first-, second-and third-generation cephalosporins
(eg ceftazidime)
monobactams (eg aztreonam)
carboxypenicillins (eg carbenicillin)
Varied susceptibility to piperacillin/tazobactam
Typically susceptible to carbapenems and
cephamycins
Often clinically and/or microbiologically
non-susceptible to fourth-generation cephalosporins

51. Clinical features of ESBLs
Even if sensitive to fourth-generation
cephalosporins
in vitro, treatment failures occur in clinical
practice
Create clinical difficulties due to cross-resistance
with other antibiotic classes (eg
aminoglycosides)
Associated with nosocomial outbreaks of high
morbidity and mortality
Result in overuse of other broad-spectrum
agents

52. Clinical failure in the
presence of ESBLs
Recent data show high clinical failure rates among patients
treated with cephalosporins for serious infections caused
by ESBL-producing pathogens
susceptible to cephalosporins in vitro
4/32 patients received cephalosporins to which
pathogens showed intermediate susceptibility and all
failed treatment
15/28 remaining patients with cephalosporin-
susceptible pathogens failed treatment and 4 died
11 patients required a change in antibiotic therapy
Paterson et al. J Clin Microbiol 2001;39:2206–2212

53. Patients who failed cephalosporin
therapy for serious infections due to
ESBL-producing organisms
Paterson et al. J Clin Microbiol 2001;39:2206–2212
Clinical failure rate (%)
0
60
100
20
1
40
80
2 4 8
Cephalosporin MIC (µg/mL)

54. Features of methicillin-resistant
Staphylococcus aureus(MRSA)
Introduction of methicillin in 1959 was
followed rapidly by reports of MRSA
isolates
Recognisedhospital pathogen since the
1960s
Major cause of nosocomial infections
worldwide
contributes to 50% of infectious morbidity in
ICUs in Europe
surveillance studies suggest prevalence has
increased worldwide, reaching 25–50% in
1997
Jones. Chest 2001;119:397S–404S

55. Seriousinfections testing positive for MRSA
isolates among hospitalised patients
(1997 SENTRY data)
Patients (%)
0
30
50
10
Pneumonia
20
40
UTI Wound Bloodstream
Infection type
Jones. Chest 2001;119:397S–404S
UTI
UTI = urinary tract infection

56. Features of MRSA: epidemic
strains
Problemescalated in the early 1980s with
emergence of epidemic strains (EMRSA)
first recognised in the UK
17 EMRSAs identified to date
Impact on hospitals is variable
presence ofEMRSA can account for >50%
of S. aureusisolates
Aucken et al. J Antimicrob Chemother2002;50:171–175

57. Risk factors for colonisation or
infection with MRSA in hospitals
Chambers. Emerg Infect Dis 2001;7:178–182
Admission to an ICU
Surgery
Prior antibiotic exposure
Exposure to an MRSA-colonised patient

58. Emergence of MRSA in the
community
MRSA in hospitals leads to an associated rise in incidence
in the community
Community-acquired MRSA strains may be distinct from
those in hospitals
In a hospital-based study, >40% of MRSA infections were
acquired prior to admission
Risk factors for community acquisition included:
recent hospitalisation
previous antibiotic therapy
residence in a long-term care facility
intravenous drug use
Colonisation and transmission are also seen in individuals
(including children) lacking these risk factors
Hiramatsu et al. Curr Opin Infect Dis 2002;15:407–413
Layton et al. Infect Control Hosp Epidemiol 1995;16:12–17; Naimi et al. 2003;290:2976−2984

59. Antimicrobial features of
MRSA(1)
Mechanism involvesaltered target site
newpenicillin-binding protein—PBP 2'(PBP
2a)
encoded by chromosomally located mecA
gene
Confers resistance to all -lactams
Gene carried on a mobile genetic element —
staphylococcal cassette chromosome mec
(SCCmec)
Laboratory detection requires care
Not all mecA-positive clonesare resistant to
methicillin
Hiramatsu et al. Trends Microbiol 2001;9:486–493
Berger-Bachi&Rohrer. Arch Microbiol 2002;178:165–171

60. Antimicrobial features of
MRSA(2)
Cross-resistance common with many other
antibiotics
Ciprofloxacin resistance is a worldwide problem
in MRSA:
involves ≥2 resistance mutations
usually involves parC and gyrA genes
renders organism highly resistant to
ciprofloxacin, with cross-resistance to other
quinolones
Intermediate resistance to glycopeptides
first reported in 1997
Hiramatsu et al. J Antimicrob Chemother 1997;40:135–136
Hooper. Lancet Infect Dis 2002;2:530–538

61. Clinical features of MRSA
Common associations include:
underlyingchronic disease,especially
repeated
hospital stays
prolonged/repeated antibiotics,especially the
-lactams
Usually susceptible to at least one other
antibiotic
Not all MRSAs behave as EMRSAs
Methicillin resistance is not a marker of
virulence

62. Clinical features of MRSA:
transmission
Occurs primarily from colonised or infected patients
via the hands of healthcare workers
contacttransmission to other patients or staff very
common
Airborne transmission important in the acquisition of
nasal carriage
Infection control measures include:
screening and isolation of new patients suspected
of carrying MRSA or S. aureuswith vancomycin
resistance
implementing infection control programmes
establishing adequate antibiotic policy to minimise
development of resistance

63. Managementof MRSA
Educateon risks and control measures
Adhere to strict control measures to prevent
transmission, especially through contact
Treatpatient with appropriate empiric
andtargeted therapy
Consider clearing patient of MRSA carriage

64. Glycopeptide resistance: focus
on vancomycin resistance
Vancomycin-resistant enterococci
(VRE)
Vancomycin-resistant S. aureus
(VRSA)

65. Features of quinoloneresistance:
Gram-negative organisms
Resistance most common in organisms associated
with nosocomial infections
Pseudomonas aeruginosa
Acinetobacter spp.
also increasing among ESBL-producing strains
Meropenem Yearly Susceptibility Test Information
Collection (MYSTIC) surveillance programme
(1997―2000)
13.4% of Gram-negative strains resistant to
ciprofloxacin
P. aeruginosaand Acinetobacter baumanniiare
the most prevalent resistant strains
increasing prevalence of resistance during
surveillance period
Masterton. J Antimicrob Chemother 2002;49:218–220
Thomson. J Antimicrob Chemother 1999;43(Suppl. A):31–40

66. Gram-negative organismswith
resistance to ciprofloxacin (1997
SENTRY data)
Organisms (%)
0
30
50
10
Stenotrophomonas
maltophilia
20
40
Acinetobacter spp.P. aeruginosa Escherichia
coli
All patients (USA)
Lower RTI (USA and Canada)
Organism type
Jones. Chest 2001;119:397S–404S

67. Features of quinoloneresistance:
Gram-positive organisms
MRSA
S. aureusoccurred in 22.9% of pneumonias in
hospitalised patients in USA and Canada (1997
SENTRY data)
Enterococcusspp. resistance
has developed rapidly, especially among VRE
Streptococcus pneumoniaeresistance
emerging in many countries, including
community-acquired resistance
Hong Kong (12.1%), Spain (5.3%) and USA
(<1%)
marked cross-resistance with other
frequently used antibiotics
Hooper. Lancet Infect Dis 2002;2:530–538

69. Summary
Antibiotic resistance in the hospital
setting is increasing at an alarming
rate
and is likely to have an important
impact on infection management
Steps must be taken now to control
the increase in antibiotic resistance
Cosgrove et al. Arch Intern Med 2002;162:185–190

70. Summary
The Academy for Infection Management supports the
concept of using appropriate antibiotics early in
nosocomial infections and proposes:
selecting the most appropriate antibiotic based on the
patient,
risk factors, suspected infection and resistance
administering antibiotics at the right dose for the
appropriate duration
changing antibiotic dosage or therapy based on
resistance and pathogen information
recognising that prior antimicrobial administration is a
risk factor for the presence of resistant pathogens
knowing the unit’s antimicrobial resistance profile and
choosing antibiotics accordingly