VentilatorAssociated

Pneumonias
(VAP)
D R.T.V.RAO M D

 Nosocomial

pneumonia (NP),
P neum onia canhospital-acquired
be a life
pneumonia
(HAP) and
threatening condi
tion
ventilator-associated
pneumonia (VAP), is
an important cause of
morbidity and
mortality in
hospitalized patients.
One of the factors
contributing to a high
mortality rate of HAP
and VAP could be
antibiotic resistance
among the causative
agents.

Ventilator A ssociated
P neum onia (VA P )
Ventilator Associated

Pneumonia (VAP) is
pneumonia occurring in
a patient within 48
hours or more after
intubation with an
endotracheal tube or
tracheostomy tube and
which was not present
before. It is also the
most common and
fatal infection of ICU

Ventilator Associated
Pneum onia (VAP)
VAP is the 2nd most common nosocomial

infection = 15% of all hospital acquired

infections
Incidence = 9% to 70% of patients on
ventilators
Increased ICU stay by several days
Increased avg. hospital stay 1 to 3 weeks
Mortality = 13% to 55%

Centers for Disease Control and Prevention, 2003.

C hallenge and
C ontroversy

The diagnosis

and
management of
VAP remains one
of the most
controversial
and challenging
topics in
management of
critically ill

C entres for D isease and C ontrol

The diagnosis of pneumonia

in mechanically ventilated
patients is difficult, and still
there is no "gold-

standard"
diagnostic
method. It is usually
based on the combination of
clinical, radiological, and
microbiological criteria
defined by Centres for

Disease and Control

(CDC)

Incidence
It is often difficult to define the exact incidence of

HAP and VAP, because there may be an overlap

with other lower respiratory tract infections, such
as tracheobronchitis, especially in mechanically
ventilated patients)
The exact incidence of HAP is usually between 5
and 15 cases per 1,000 hospital admissions
depending on the case definition and study
population; the exact incidence of VAP is 6- to
20-fold greater than in nonventilated patients

M echanicalventilation predisposes to
VAP
HAP accounts

for up to 25% of
all ICU infections
In ICU patients,
nearly 90% of
episodes of HAP
occur during
mechanical
ventilation

N osocom ialinfection are

M ultidrug Resistant
Many patients with HAP,

VAP, and HCAP are at

increased risk for
colonization and infection
with MDR pathogens
HAP and VAP are a

frequent cause of
nosocomial infection that is
associated with a higher
crude mortality than other
hospital-acquired infections
9

D ef n
i ition Ventilator A ssociate
Pneum onia
Pneumonia that develops in someone
who has been intubated
-Typically in studies, patients are only
included if intubated greater than 48
hours
-Early onset= less than 4 days
-Late onset= greater than 4 days

Endotracheal intubation increases risk of

developing pneumonia by 6 to 21 fold
Accounts for 90% of infections in
mechanically ventilated patients

P revalence of VA P
Occurs in 10-20%

of those receiving
mechanical
ventilation for
greater than 48
hours
Rate= 14.8 cases
per 1000 ventilator
days

W hen does VAP occur?

Cook et al showed . . .
40.1% developed before day 5
41.2% developed between days 6 and

10
11.3% developed between days 11-15
2.8% developed between days 16 and
20
4.5% developed after day 21
Cook et al. Incidence of and risk factors for ventilator-associated pneumonia
in critically ill patients.

Tim e fram e of intubation

and risk
Risk of

pneumonia at
intubation days
3.3% per day at

day 5
2.3% per day at
day 10
1.3% per day at
day 15

W ho gets VA P ? (R isk factors)

Study of 1014 patients receiving

mechanical ventilation for 48 hours or

more and free of pneumonia at
admission to ICU
Increased risk associated with
admitting diagnosis of :
Burns (risk ratio=5.09)
Trauma (risk ratio=5.0)
Respiratory disease (risk ratio=2.79)
CNS disease (risk ratio=3.4)

16

PAH O G EN ESIS
The pathogenesis of

ventilatorassociated
pneumonia usually
requires that two
important
processes take
place:
Bacterial colonization
of the aero digestive
tract
The aspiration of
contaminated
secretions into the

17

18

Etiology
Bacteria cause most

cases of HAP, VAP,

and HCAP and
many infections are
polymicrobial; rates
are especially high
in patients with
ARDS
19

VA P Etiolog y

Most are
are bacterial
bacterial
pathogens, with
with Gram
Gram
negative bacilli common:
common:

Pseudomonas

aeruginosa

Proteus spp
Acinetobacter spp

Staphlococcus aureus
Early VAP associated with
non-multi-antibioticresistant organisms
Late VAP associated with
antibiotic-resistant
organism

C om m on and U ncom m on
isolates in VA P
HAP, VAP, and HCAP are

commonly caused by
aerobic gram-negative
bacilli, such as P.
aeruginosa, K. pneumoniae,
and Acinetobacter species,
or by gram-positive cocci,
such as S. aureus, much of
which is MRSA; anaerobes
are an uncommon cause of
VAP

D rug resistance a concern in

Ventilator Associated Pneum onias
A. baumanni was the

most common isolated

pathogen many of
them were multidrugresistant (MDR) or pan
drug-resistant (PDR).
The other common
isolated pathogens
were K. pneumoniae,
P. aeruginosa and
methicillin-resistant
S. aureus (MRSA).

O ther Isolates in Ventilator

associated Pneum onias
Pseudomonas aeruginosa.
the most common MDR gram-negative bacterial pathogen
causing HAP/VAP, has intrinsic resistance to many
antimicrobial agents

Klebsiella, Enterobacter, and Serratia species.

Klebsiella species
intrinsically resistant to ampicillin and other
aminopenicillins and can acquire resistance to
cephalosporins and aztreonam by the
production of extended-spectrum lactamases
(ESBLs)
However ESBL-producing strains remain
susceptible to carbapenems

Enterobacter species

23

Acinetobacter species

AcinAcinetobacter

species

Acinetobacter species

More than 85% of

isolates are
susceptible to
carbapenems, but
resistance is
increasing
Stenotrophomonas
maltophilia, and
Burkholderia cepacia:
resistant to
carbapenems

24

Acinetobacter species a
Growing Concern
Acinetobacter species
More than 85% of isolates are susceptible
to carbapenems, but resistance is
increasing
An alternative for therapy is sulbactam
Stenotrophomonas maltophilia, and
Burkholderia cepacia:

Resistant to carbapenems
Susceptible to trimethoprim
sulfamethoxazole, ticarcillin
clavulanate, or a fluoroquinolone

Staphylococcus aureus and

Streptococcus pneum oniae
Methicillin-resistant Staphylococcus

aureus
vancomycin-intermediate S. aureus
sensitive to linezolid
linezolid resistance has emerged in S.
aureus, but is currently rare

Streptococcus pneumoniae and

Haemophilus influenzae.
sensitive to vancomycin or linezolid, and
most remain sensitive to broadspectrum
quinolones
26

L. Pneumophila and environment

Rates of L.

pneumophila vary
considerably between
hospitals and disease
occurs more commonly
with serogroup 1 when
the water supply is
colonized or there is
ongoing construction

27

Inf u
l enza too can cause
VA P

Nosocomial virus and fungal

infections are uncommon

causes of HAP and VAP in
immunocompetent patients.
Outbreaks of influenza have
occurred sporadically and
risk of infection can be
substantially reduced with
widespread effective infection
control, vaccination, and use
of anti influenza agents

28

Fungalpathogens
can cause
Fungal
VAP pathogen

s.
Aspergillu
s species
Candida
albicans

Pathogenesis Entry of
Pathogens
Where do the bacteria come from?
Tracheal colonization- via oropharyngeal

colonization or GI colonization
Ventilator system

How do they get into the lung?

Breakdown of normal host defenses
Two main routes
Through the tube
Around the tube- microaspiration around
ETT cuf

Causative Organisms
Early onset:

Hemophilus influenza
Streptococcus pneumoniae
Staphylococcus aureus (methicillin sensitive)
Escherichia coli
Klebsiella pneumoniae

Late onset:

Pseudomonas aeruginosa
Acinetobacter spp.
Staphylococcus aureus (methicillin resistant)

Most strains responsible for early onset VAP are

antibiotic sensitive. Those responsible for late

onset VAP are usually multiple antibiotic resistant
(1995)

Am J Resp Crit Care

O ropharyngeal
colonization can be source
Scannapieco etof
al showed
VA P a transition

in the colonization of dental plaques in

patients in the ICU
Control=25 subjects presenting to
preventive dentistry clinic
Study group=34 noncardiac patients
admitted to medical ICU at VA hospital
(sampled within 12 hours of admission
and every third day)

G astrointestinal colonization
Increased gastric pH leads to

bacterial overgrowth
Reflux can then lead to colonization
of oropharynx
Use of antacids and H2 blockers
associated with GI colonization

Safdar et al. The pathogenesis of ventilator-associated

pneumonia:
its relevance to developing efective strategies for

V iral Pathogens
Outbreaks of HAP,
VAP, and HCAP due to
viruses, such as
influenza,
parainfluenza,
adenovirus, measles,
and respiratory
syncytial virus have
been reported and
are usually seasonal.
Influenza,
pararinfluenza,
adenovirus, and
respiratory syncytial
virus account for 70%
of the nosocomial

M ultidrug resistant organism s are

associated w ith
The prevalence of MDR

pathogens varies by patient

population, hospital, and type
of ICU, which underscores the
need for local surveillance
data
MDR pathogens are more
commonly isolated from
patients with severe, chronic
underlying disease, those with
risk factors for HCAP, and
patients with late-onset HAP
or VAP
35

S upine patients
Studies using radioactive labeling of

gastric contents showed that radioactive

counts were higher in larynx of supine
patients
One of the studies showed the same
organisms in stomach, pharynx and
endobronchial samples1
Drakulovic et al. studied rate of VAP and
found it to be higher in supine compared
to semi-recumbent patients

Tracheal colonization
Cendrero et al:
25 patients of 110 studied developed

VAP
In these 25 patients, 22 had their
trachea colonized 3.63 days prior to
diagnosis of VAP
17 of the 22 had oropharyngeal
colonization prior to trachea
Only 7 had prior colonization of the
stomach

Infected biofilms too contribute to increased

incidence of VAP
Infected biofilm in

the endotracheal
tube, with
subsequent
embolization to
distal airways, may
be important in the
pathogenesis of VAP

ET tubes increases B iof l

im
form ation
Exopolysaccharide

outer layer with

quiescent bacteria
within
Difficult for bacteria

to penetrate outer
layer and bacteria
within resistant to
bactericidal efects
of bacteria

D if c
i
fult to killbiofi
lm organism s
Com parison ofM BC ofantibiotics fortrachealisolates vs.biofi
lm isolates

Organism

Tobramycin

Cefotaxime

Cefuroxime

P. aeruginosa
-Tracheal
-ET

256
>1024

32
>1024

>1024
>1024

Enterobacteriaceae
-Tracheal
-ET

4
>1024

128
256

32
512

S. aureus
-Tracheal
-ET

18
>1024

16
128

16
>1024

C linical Strategy in
D iagnosis of VA P
Clinical Strategy
The presence of a new or progressive
radiographic infiltrate
At least two of three clinical features
fever greater than 38_C,
leukocytosis or leukopenia,
purulent secretions

Represents the most accurate

combination of criteria for starting
empiric antibiotic therapy.
41

Pathogens in VA P (1)
Pathogens that

cause VAP difer

depending on
whether the
condition occurs
early (less than 96
hours after
intubation or
admission to ICU)
or late (greater
than 96 hours after

Pathogens in VA P (2 )
EarlyOnset Pneumonia

(< 96 hours of
intubation or ICU
admission)
Community-acquired
Pathogens:
Streptococcus
pneumoniae
Haemophilus
influenzae
Staphylococcus aureus
Antibiotic-sensitive ?

Pathogens in VAP (3)

Late-Onset

Pneumonia (> 96
hours of intubation
or ICU admission)
Hospital-acquired
Pathogens:
Pseudomonas aeruginosa
Methicillin resistant
Staphylococcus aureus
(MRSA)
Acinetobacter
Enterobacter

Antibiotic-resistant ???

D iagnosis is im precise and usually

based on a Com bination of
Clinical factors - fever or

hypothermia; change in secretions;

cough; apnea/ bradycardia; tachypnea

Microbiological factors - positive

cultures of blood/sputum/tracheal
aspirate/pleural fluids

CXR factors - new or changing

infiltrates

Strategies in D iagnosis in
VA P are m ultifaceted

Clinical

Strategy
Bacteriologi
c Strategy
Comparing
Diagnostic
Strategy

46

Gram stain is highly

sensitive
Sputum or tracheal suction gram stain
NO ORGANISMS
in non-neutropenic pts.

NO HAP/VAP 94%

G ram staining of secretions

are useful in early decisions
The upper respiratory

tract of patients is
colonized with potential
pulmonary pathogens a
few hours after
intubation.
A positive Gram's
stain may guide the initial
antibiotic therapy.
However prior antibiotic
and corticosteroid therapy
can reduce the sensitivity
of this technique

Bacterial culture of tracheal

secretion

Qualitative culture
- non specific
Semi-quantitative
culture
- low specificity
Quantitative culture
: TS, BAL, PSB
- increase
specificity

Specim en collection for

O ptim al R esults
Distal airway samples may be

obtained by using bronchoscopic or

nonbronchoscopic techniques.
Withnonbronchoscopic techniques, a
catheter is blindly advanced through
the endotracheal tube or
tracheostomy and wedged in the
distal airway. Various sampling
methods include blind bronchial
suction (BBS), blind BAL, and blind
PSB sampling.

Semiquantitative
1+ : rare
<10 colonies/plate
2+: few
10-102 colonies/plate
3+: moderate >102-3 colonies/plate
4+: numerous >103-4 colonies/plate
5+: numerous >104 colonies/plate

Tracheal aspirates are

valuable specim ens
A reliable tracheal aspirate

Gram stain can be used to

direct initial empiric
antimicrobial therapy and may
increase the diagnostic value
of the CPIS
A negative tracheal aspirate
(absence of bacteria or inflammatory cells) in a patient
without a recent (within 72
hours) change in antibiotics
has a strong negative
predictive value (94%) for
VAP and should lead to a
search for alternative sources
of fever
52

Bacteriologic Strategy
Quantitative cultures can be

performed on endotracheal
aspirates or samples collected
either bronchoscopically or
nonbronchoscopically, and
each technique has its own
diagnostic threshold and
methodologic limitations. The
choice of method depends on
local expertise, experience,
availability, and cost

Bacterial culture of tracheal

secretion

Qualitative culture
- non specific
Semi-quantitative culture
- low specificity
Quantitative culture : TS, BAL, PSB
- increase specificity

C ollection of bronchial
Secretions
Distal airway samples may be

obtained by using bronchoscopic or

nonbronchoscopic techniques.
Withnonbronchoscopic techniques, a
catheter is blindly advanced through
the endotracheal tube or
tracheostomy and wedged in the
distal airway. Various sampling
methods include blind bronchial
suction (BBS), blind BAL, and blind
PSB sampling.

Q ualitative and quantitative

Qualitative endotracheal aspirates
are easy to obtain but have a high
false-positive rate in ICU
patientsbecause ofairway
colonization. When
quantitativeendotracheal-aspirate
culturesare used, a cutof value of
106 is the most accurate, with a
sensitivityof 38-82% and a
specificity of 72-85%

False negative False P ositive

R esults
Investigators reported

that the clinical

diagnosis of VAP is
associated 3035%
false-negative and 20
25% false-positive
results . And also, ICU
patients do not always
have systemic signs of
infection due to their
underlying disease
(chronic renal failure)

O ther Supporting B acterial

C ultures
Bacteraemia and positive pleural efusion

cultures are generally considered to be

able to identify the organisms causing the
pneumonia, if no other source of infection
is found. Therefore, most experts
recommend that investigation of
suspected VAP should include taking two
sets of blood samples for culture and
tapping pleural >10mm, even though
spread to the blood or pleural space
occurs in<10% of VAP

M ultiresistant pathogens in
Ventilator associated pneum onias
The incidence of

multiresistant
pathogens is also
closely linked to local
factors and varies
widely from one
institution to another.
Consequently, each
ICU must continuously
collect meticulous
epidemiologic data

U ncom m on m icrobes are

Legionella species ,
often m issed

anaerobes fungi viruses,

and even Pneumocystis
carinii should be
mentioned as potential
causative agents but are
not considered to be
common in the context of
pneumonia acquired
during MV. However,
several of these causative
agents may be more
common and potentially
underreported because of
difficulties involved with
the diagnostic

C om paring D iagnostic
Strategy
A patients with suspected VAP should have a lower

respiratory tract sample sent for culture, and

extrapulmonary infection should be excluded, as
part of the evaluation before administration of
antibiotic therapy
If there is a high pretest probability of pneumonia,
or in the 10% of patients with evidence of sepsis,
prompt therapy is required, regardless of whether
bacteria are found on microscopic examination of
lower respiratory tract samples

61

M icrobiologists / P hysicians should

consider other D iagnostic results
Pugin et al. proposed to

combine the seven

variables (temperature,
leukocytes, tracheal
aspirate volume and
purulence of tracheal
secretions, chest X-ray,
oxygenation-PaO2/FiO2and semi quantitative
culture of tracheal
aspirate) for the diagnosis
of VAP, defined as clinical
pulmonary infection score
(CPIS)

Evidence-based early and appropriate

therapy in VAP
Mortality
Inappropriate

Mortality

Appropriate

Mortality

Early

Mortality

B est option in choosing

A ntibiotics
Considerations in making selection
Setting (community, NH, hospital)
Suspected organism (GNRs, GPCs)
Host factors (immunosuppression)
Local susceptibility patterns

Initial empiric and broad; subsequent

narrowing
Concept is to not miss the organism with

initial coverage and then de-escalate when

able

C ontinuous R em oval of
Subglottic Secretions

Use an ET tube
with continuous
suction through a
dorsal lumen above
the cuff to prevent
drainage
accumulation

HOB Elevation
HOB at 30-

o
Keep the HOB
elevated to at least 30
degrees unless
medically
contraindicated

45

C ondensate
Heat-moisture
exchanger ent
m anagem

Theoretical advantage=prevents bacterial

colonization of tubing
Studies= Mixed results
Disadvantage=increases dead space and
resistance to breathing

Heated wire to elevate temp of inspired

air
Advantage=Decreases condensate formation
Disadvantage=Blockage of ET tube by dried

secretions

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

Condensate m anagem ent

Nurse and provider

education
regarding
management of
tubes with patient
position change or
manipulation of
bed to ensure that
condensate in
tubing does not
flow towards

H andw ashing
What role does handwashing
play in nosocomial
pneumonias?
The
greatest role

VAP Prevention
Wash hands before

and after suctioning,

touching ventilator
equipment, and/or
coming into contact
with respiratory
secretions.

Epidem iologicaldata diff

ers from
situations
The incidence of

multiresistant
pathogens is also
closely linked to local
factors and varies
widely from one
institution to another.
Consequently, each
ICU must continuously
collect meticulous
epidemiologic data

Treating patient w ith VA P is

com plex
Successful treatment of patients with

VAP remains a difficult and complex

undertaking. Despite broad clinical
experience with this disease, no
consensus has been reached
concerning issues as basic as the
optimal antimicrobial regimen or its
duration. In fact, to date, evaluation
of various antimicrobial strategies for
the treatment of bacterial VAP has
been difficult for several reasons.

Sum m ary
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

Created by Dr.T.V.Rao MD for e

learning for Medical Professionals
Email
doctortvrao@gmail.com