The seminar discusses ventilator-associated pneumonia (VAP), a serious form of pneumonia that occurs in mechanically ventilated patients, highlighting its epidemiology, etiology, clinical presentation, diagnosis, and treatment. VAP is linked to significant mortality rates and requires accurate diagnosis to guide appropriate treatment while avoiding antibiotic resistance. Key factors in its pathogenesis include bacterial colonization, aspiration, and compromised host defenses, with diagnostic approaches favoring invasive sampling to improve specificity.

1. Seminar on ventilator associated
pneumonia
Addisu. N (R1)
Moderator; Dr. Amsalu ( senior consultant and PCCM)
25/6/2021

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outline
• Definition
• Epidemiology
• Etiology
• Clinical presentation
• Diagnosis
• Treatment
• prevention

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• Endotracheal intubation and MV have direct and indirect effects on
the lung and upper airways, the cardiovascular and the
gastrointestinal system.
• Pulmonary complications include
- barotrauma,
- nosocomial pneumonia,
-oxygen toxicity,
- tracheal stenosis, and
-deconditioning of respiratory muscles.

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VENTILATOR-ASSOCIATED
PNEUMONIA
Ventilator-associated pneumonia (VAP) is a type of hospital-
acquired pneumonia that develops after more than 48 hours of
mechanical ventilation.
 Clinical definition of VAP
• diagnosed when a patient who has been mechanically ventilated for
48 hours develops
≥ a new or progressive infiltrate with associated
signs and symptoms of infection (eg, new onset of fever, purulent
sputum, leukocytosis, decline in oxygenation, altered respiratory
mechanics) and the respiratory specimens are positive (ie, increased
neutrophils are seen in the microscopic analysis and growth of a
pathogen in culture exceeds a predefined threshold).

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VAP is a common and serious problem in the intensive care unit that is
associated with an increased risk of death(50-70%.)
• Accurate diagnosis is important so that appropriate treatment can be
instituted early while simultaneously avoiding antibiotic overuse and
consequently, antibiotic resistance

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EPIDEMIOLOGY
• common complication among patients requiring mechanical
ventilation.
• Prevalence estimates vary between 6 and 52 cases per 100 patients,
depending on the population studied.
• US epidemiological studies report an incidence of VAP of 2–16
episodes per 1000 ventilator-days.
• estimated the risk of VAP to be 3% per day during the first 5 days on
mechanical ventilation, 2% per day from day 5 to 10 and 1% per day
for the remaining days
• Cumulative risk as long as 30 day is 70%

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ETIOLOGY
• include both MDR and non-MDR bacterial pathogens.
• non-MDR group
nearly identical to the pathogens found in severe CAP
develops in the first 5–7 days of the hospital stay(early onset VAP)
MDR pathogens
 common after 5 days of hospital stay(late onset VAP)
 consider early of there is risk factor.
vary significantly
Most hospitals have problems with P. aeruginosa and MRSA, but
other MDR pathogens are often institution-specific.
fungal and viral pathogens

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• Of 8474 cases of VAP reported to the United States Centers for
Disease Control and Prevention from 2009 to 2010, the distribution of
pathogens associated was
• S. aureus (24.1 percent),
• P. aeruginosa (16.6 percent),
• Klebsiella species (10.1 percent),
• Enterobacter species (8.6 percent),
• Acinetobacter baumannii (6.6 percent), and
• E. coli (5.9 percent).

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pathogenesis
• Three factors are critical in the pathogenesis of VAP:
1. colonization of the oropharynx with pathogenic
microorganisms,
2. aspiration of these organisms from the oropharynx into
the lower respiratory tract, and
3. compromise of the normal host defense mechanisms

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• The most obvious risk factor is the endotracheal tube,
- bypasses the normal mechanical factors
- exacerbated microaspiration
- facilitating tracheal colonization.
- surface for glycocalyx biofilm formation
- suctioning dislodged bacteria and can reinoculate the trachea, or tiny
fragments of glycocalyx can embolize to distal airways, carrying
bacteria with them.

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colonization
• In a high percentage of critically ill patients, the normal
oropharyngeal flora is replaced by pathogenic
microorganisms. The most important risk factors are
 antibiotic selection pressure,
cross-infection from other infected/colonized patients or
contaminated equipment, and
 malnutrition.
• only around one-third of colonized patients develop VAP.

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host defenses
• final step in VAP development, independent of aspiration
and oropharyngeal colonization, is the overwhelming of
host defenses.
 immunosuppression
Hyperglycemia
 more frequent transfusions
underling disease

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CLINICAL MANIFESTATIONS
generally the same in VAP as in all other forms of pneumonia:
Signs – fever, tachypnea, increased or purulent secretions,
hemoptysis, rhonchi, crackles, reduced breath sounds, bronchospasm
Ventilator mechanics – reduced tidal volume, increased inspiratory
pressures
Laboratory findings – worsening hypoxemia, leukocytosis
Features may also be accompanied by systemic abnormalities, such as
encephalopathy or sepsis.

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• Importantly, as isolated findings, none of these features are
sensitive or specific for the diagnosis of VAP.
• In particular, fever and respiratory distress are common among
intubated patients with a wide variety of etiologies that must also be
considered.

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Imagining
• The chest radiograph can help to diagnose, to determine the severity
of the disease (multilobar versus unilobar) and identify complications,
such as pleural effusions or cavitation.
• The frequency of abnormal chest radiographs before the onset of
pneumonia in intubated patients and the limitations of portable
radiographic technique make interpretation of radiographs more
difficult than in patients who are not intubated.
• new or progressive infiltrate on chest radiograph or computed
tomography (CT)

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DIAGNOSIS
• No single set of criteria
• Application of the clinical criteria typical for CAP consistently results in
overdiagnosis of VAP
1) frequent tracheal colonization with pathogenic bacteria in patients
with endotracheal tubes,
2) multiple alternative causes of radiographic infiltrates in
mechanically ventilated patients, and
3) the high frequency of other sources of fever in critically ill patients.

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• diagnostic dilemma
invasive sampling methods with quantitative cultures VS
noninvasive sampling with semiquantitative cultures

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• the 2017 guidelines issued by The European Respiratory
Society (ERS)/European Society of Intensive Care
Medicine (ESCIM)/European Society of
Clinical Microbiology/Infectious Diseases (ESCMID)/Asociación Latino
americana del Tórax (ALAT), state a preference for invasive sampling
methods with quantitative cultures.
high diagnostic accuracy
 the potential to reduce antibiotic exposure,
thereby promoting good antibiotic stewardship.
• recommend obtaining a lower respiratory tract sample (distal
quantitative or proximal quantitative or qualitative culture) to focus
and narrow the initial empiric antibiotic therapy. (Strong
recommendation, low quality of evidence.)

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• The Infectious Diseases Society of America/The American Thoracic
Society, have preference for noninvasive sampling with
semiquantitative cultures for the diagnosis of VAP; this preference
is based upon evidence that demonstrates
no difference in mortality or
length of stay with either approach
Overall mortality, ICU length of stay and duration of mechanical
ventilation did not show differences between the two interventions
in a pooled analysis.

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Quantitative-Culture Approach
• The essence is discrimination between colonization and true
infection through determination of the bacterial burden.
• The more distal in the respiratory tree the diagnostic sampling, the
more specific the results and therefore the lower the threshold of
growth necessary to diagnose pneumonia and exclude colonization.
• VAP is supported when an established threshold of bacterial growth is
exceeded.
•Endotracheal aspirates – 1,000,000 cfu/mL
≥
•Bronchoscopic- or mini-BAL – 10,000 cfu/mL
•PSB – 1000 cfu/mL

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• Additional tests that may increase the diagnostic yield include Gram’s
staining, differential cell counts, staining for intracellular organisms,
and detection of local protein levels elevated in response to
infection.
• The key piece of a quantitative-culture approach is to base
subsequent antibiotic therapy on the results of the quantitative
cultures.
• antibiotic treatment was initiated only in patients whose gram
stained respiratory sample was positive or who displayed signs of
hemodynamic instability.

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Microscopic analysis –
• This involves semi-quantitative analysis of PMN leukocytes and other
cell types, as well as the Gram stain.
• the microscopy results return before cultures and can be helpful in
determining a possible pathogen and alter antibiotic selection.
• The presence of abundant neutrophils (>25/LPF) is consistent with
VAP and the bacterial morphology may suggest a likely pathogen (eg,
Gram-negative rods).

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In a study comparing the quantitative with the clinical approach, the
use of bronchoscopic quantitative cultures
resulted in significantly less antibiotic use at 14 days after study
a lower 14-day mortality rate,
a lower 28-day severity-adjusted mortality rate.
more alternative sites of infection were found.
• expertise in quantitative-culture techniques is critical, with a
specimen obtained as soon as pneumonia is suspected and before
antibiotic therapy is initiated or changed.

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• BAL
involves the infusion and aspiration of sterile saline through a flexible
bronchoscope that is wedged in an affected bronchial segmental or
subsegmental
PSB
is a brush that is contained within a protective sheath, which minimizes
the likelihood that the brush will be contaminated during
bronchoscopy.
Mini-BAL is performed by advancing a catheter through the
endotracheal tube blindly until resistance is meet, infusing sterile saline
through the catheter and then aspirating using the syringe (the
catheter is estimated to be located in the distal endobronchial airway

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disadvantage of bronchoscopic sampling
 only performed by physicians with expertise in the procedure.
 it is more invasive and
ventilated patients are at risk of complications including worsening
hypoxemia and barotrauma.

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Quantitative-Culture Approach
• Advantage
• High specificity
• Reduce antibiotic exposure
• Reduce antibiotic resistance
• More other site of infection
found.
• Disadvantage
• low sensitivity
• Need expertise
• Expensive

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Clinical Approach
• Base on Tracheal aspirates sample
• have low specificity and High sensitivity
• over diagnosis and over treatment; antibiotic resistance
the absence of an MDR pathogen in tracheal aspirate cultures
eliminates the need for MDR coverage, allowing empirical antibiotic
therapy to be de-escalated.

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• Noninvasive respiratory sampling —
• Tracheobronchial aspiration is performed by advancing a catheter
through the endotracheal tube until resistance is met and suction is
applied (likely located in trachea or main stem bronchus). The
sample is directly aspirated into a sterile specimen trap that can be
sent for microbiologic analysis.

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• Generally speaking, compared with quantitative cultures derived
from bronchoscopic specimens, quantitative cultures derived
from nonbronchoscopic specimens have similar or higher
diagnostic sensitivity (ie, low false negative rate) but a lower
specificity (ie, higher false-positive rate).
 the approach at each institution, or potentially for each
patient, should balance the frequency of complex illnesses
that are associated with
(1) greater frequency of alternative causes of the clinical
manifestations,
(2) higher colonization rates, and
(3) more frequent prior antibiotic therapy versus availability and
expertise of invasive techniques with quantitative cultures.

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Treatment
• Treatment should be started once diagnostic specimens
have been obtained.
• higher mortality rates with initially inappropriate empirical
antibiotic therapy
• an appreciation of the resistance patterns of the most
likely pathogens in a given patient

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ANTIBIOTIC RESISTANCE
• Global threat
• Frequent use of β-lactam drugs, especially cephalosporins,
appears to be the major risk factor for infection with MRSA
and extended-spectrum β-lactamase–positive strains.

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EMPIRICAL THERAP
the presence of risk factors for MDR pathogens
 local patterns of resistance
the patient’s prior antibiotic exposure.
The agents PD properties
• The majority of patients without risk factors for MDR
infection can be treated with a single agent and with the
same antibiotics used for severe CAP.
• <10% in some ICUs and is unknown for HAP patients
• lower incidence of atypical pathogens

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• The standard recommendation for patients with risk factors
for MDR infection is for three antibiotics:
two directed at P. aeruginosa and one at MRSA
A β-lactam agent provides the greatest coverage, yet even the
broadest-spectrum agent—a carbapenem—still provides
inappropriate initial therapy in up to 10–15% of cases at some
centers.

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SPECIFIC TREATMENT
• Once an etiologic diagnosis is made, broad-spectrum empirical therapy
can be modified to specifically address the known pathogen.
• antibiotics should be discontinued or that a search for an alternative
diagnosis should be pursued
A negative tracheal-aspirate culture or growth below the threshold for
quantitative cultures of samples obtained before any antibiotic change.
 A 7- or 8-day course of therapy is just as effective as a 2-week course
and is associated with less frequent emergence of antibiotic-resistant
strains.
Current guidelines recommend against continued combination therapy
for most cases of Pseudomonas pneumonia.

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FAILURE TO IMPROVE
• MRSA is associated with a 40% clinical failure rate when treated with
standard-dose vancomycin(time dependent killing)
• Linezolid appears to be 15% more efficacious than even adjusted-
dose vancomycin and is clearly preferred in patients with renal
insufficiency and those infected with high-MIC isolates of MRSA.
• Pseudomonas has a 40–50% failure rate, no matter what the regimen.
• the emergence of β-lactam resistance during therapy is an important
problem, especially in infection with Pseudomonas and Enterobacter

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• Treatment failure is very difficult to diagnose early in the
therapeutic course, and discrimination among the various
potential causes is a challenge.
new superinfection,
the presence of extrapulmonary infection,
 drug toxicity and
 complication

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COMPLICATIONS
• prolongation of mechanical ventilation, with corresponding
increases in the duration of ICU stay and hospitalization
• necrotizing pneumonia (e.g., that due to P. aeruginosa) can
cause significant pulmonary hemorrhage or long-term
complications of bronchiectasis and parenchymal scarring.
• muscle loss and general debilitation

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FOLLOW-UP
• Clinical
usually evident within 48–72 h of the initiation of
antimicrobial treatmen
• Laboratory
Serial measurements of procalcitonin levels and
inflammatory marker.
• Microbiologic
repeat quantitative cultures

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PROGNOSIS
• crude mortality rates as high as 50–70%, but the real issue is
attributable mortality.
• Attributable mortality varies(up to 25%)
• Attributable VAP mortality is defined as the percentage of deaths that
would not have occurred in the absence of the infection
 The causative pathogen also plays a major role
• MDR pathogens are associated with significantly greater attributable
mortality than non-MDR pathogens.

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PREVENTION

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Reference
• Harrison’s 20 edition
• Up to date 2018
• marino's the ICU book 4th edition

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•Thank you