2. Definition
HAP is defined as infection of the pulmonary parenchyma
that occurs 48 hours or more after admission, which
was not incubating at the time of admission.
VAP refers to pneumonia that arises more than 48–72
hours after endotracheal intubation.
VAT is characterized by signs of respiratory infection,
without new radiologic infiltrates.
HCAP includes any patient who was hospitalized in an
acute care hospital for two or more days within 90 days
of the infection; resided in a nursing home or long-
term care facility; received recent intravenous
antibiotic therapy, chemotherapy, or wound care
within the past 30 days of the current infection; or
attended a hospital or hemodialysis clinic. HCAP need
therapy for MDR pathogens.
3. Incidence
Infections involving the lungs are the most common
nosocomial infections in ICU patients, accounting for
65% of all nosocomial infections.
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.
Over 90% of ICU-acquired pneumonias occur during
mechanical ventilation, and 50% of these VAPs begin
in the first 4 days after intubation.
VAP develops in 10% to 20% of patients who undergo
mechanical ventilation for longer than 24 hours and
is associated with longer ICU stays, increased costs,
and increased mortality.
4. Etiology
Unlike community acquired
pneumonias, where the
predominant pathogens are
pneumococci,atypical organisms,
and viruses, three-quarters of
the isolates in VAP are Gram-
negative aerobic bacilli such as
(Pseudomonas aeruginosa,
K. pneumoniae, Acinetobacter
species) and Staphylococcus
aureus.
VAP may be due to
polymicrobial infections, but
rarely due to anaerobes, viral
and fungal pathogens especially
in the immunocompetent hosts.
5.
6. Patients with early-onset VAP who have received prior
antibiotics or who have had prior hospitalization within the past
90 days are at greater risk for colonization and infection with
MDR pathogens and should be treated similar to patients with
late-onset VAP.
7. Risk Factors For VAP
• Major risk factor = Endotracheal intubation
• Factors that enhance colonization of the oropharynx &/or stomach:
– Administration of antibiotics
– Admission to ICU
– Underlying chronic lung disease
• Conditions favoring aspiration into the respiratory tract or reflux from
GI tract:
– Supine position *GERD
– NGT placement *Coma/delirium
– Intubation and self-extubation
– Immobilization
• Surgery of head and neck, thorax & upper abdomen
• Host Factors:
– Extremes of age
– Malnutrition
– Immunocompromised
– Underlying condition/disease process
8. Pathogenesis
Sources of infection for HAP include healthcare devices
or the environment (air, water, equipment, and
fomites) and can occur with transfer of microorganisms
between staff and patients.
HAP requires the entry of microbial pathogens into the
lower respiratory tract, followed by colonization, which
can then overwhelm the host’s mechanical (ciliated
epithelium and mucus), humoral (antibody and
complement), and cellular (polymorphonuclear
leukocytes, macrophages, and lymphocytes and their
respective cytokines) defenses to establish infection.
9. ASPIRATION – PRIMARY ROUTE OF
BACTERIAL ENTRY INTO LRT
MICROASPIRATION
Mucociliary
clearance
Halved after
2hrs of
intubation
Mostly GNBs
Mostly GNBs
10. BIOFILM FORMATION
ANOTHER MAIN MECHANISM
• It is an aggregate of micro-organisms kept
together within a complex matrix of
polysaccharides, proteins and DNA.
• Develops within hours of intubation.
• Provides mechanical scaffold around bacteria.
• Protects against host defences and antibiotics.
11.
12. Aspiration of oropharyngeal pathogens or leakage
of bacteria around the endotracheal tube cuff is
the primary route of bacterial entry into the
trachea.
Colonization of the endotracheal tube with bacteria
encased in biofilm may result in embolization into
the alveoli during suctioning or bronchoscopy.
Inhalation of pathogens from contaminated
aerosols, and direct inoculation, hematogenous
spread from infected intravenous catheters, and
bacterial translocation from the gastrointestinal
tract lumen are uncommon pathogenic
mechanisms.
13. Diagnosis
The traditional clinical criteria for the diagnosis of VAP
includes :-
(a) fever or hypothermia,
(b) leukocytosis or leukopenia,
(c) an increase in volume of respiratory secretions or a
change in character of the secretions,
(d) a new or progressive infiltrate on the chest x-ray .
When fever, leukocytosis, purulent sputum, and a positive
culture of a sputum or tracheal aspirate are present
without a new lung infiltrate, the diagnosis of
nosocomial tracheobronchitis should be considered .
Unfortunately, in patients who are suspected of having
VAP based on these clinical criteria, the incidence of
pneumonia on postmortem exam is only 30%.
14. In both studies, the clinical criteria for identifying VAP were just as
likely to occur in the presence or absence of pneumonia. These
studies demonstrate that the diagnosis of VAP is not possible
using clinical criteria alone.
The clinical approach is overly sensitive, and patients can be
treated for pneumonia when another non-infectious process is
responsible for the clinical findings.
15. Noninfectious Causes Of Chest Infiltrates
• Atelectasis: It is common in postoperative period
following upper abdominal surgery due to
hypoventilation. Left lower lobe atelectasis is very
common following coronary artery bypass
grafting.
• Aspiration: Right lower lobe is commonly
involved. Infiltrates may take up to 12 hrs to
appear in the chest x-ray after the event.
• Pulmonary embolism: It is generally acute onset
in the background of risk factors for deep venous
thrombosis and pulmonary embolism (PE).
16. • Cardiogenic pulmonary edema.
• Acute respiratory distress syndrome (ARDS) :
The most common non-infectious cause of
pulmonary infiltrates in ICU patients. ARDS is an
inflammatory disorder of the lungs that produces
bilateral infiltrates on chest x-ray.
• Fluid overload.
• Drug reactions.
• Cryptogenic organizing pneumonia.
• Pulmonary hemorrhage.
17.
18.
19. Clinical Pulmonary Infection Score (CPIS)
The CPIS ( developed by Pugin & co-workers) combines clinical,
radiographic, physiological (PaO2/FiO2), and microbiologic data
into a single numerical result. Baseline is calculated from the first
five variables. For positive culture, two points are added to the
CPIS baseline score. A score of more than six at baseline or after
incorporating the culture result is considered suggestive of
pneumonia (sensitivity 77% and specificity 42%).
20. MODIFIED CPIS
• Given by Singh and colleagues.
• Include all criteria of CPIS except culture.
• Instead, use gram staining of BAL or PSB sample
which is reported as +ve or –ve.
• Advantage - Can be used for screening.
• Used to direct initial empiric antibiotic therapy and
may increase the diagnostic value of CPIS.
21. National Health Safety Network
Algorithm,2013
• Given to overcome the subjectivity & variability of VAP
diagnosis.
• Based on objective and recordable data.
• Ventilator associated events, in form of algorithm.
• Include 3 tiers: VAC, IVAC, PVAP.
• Include all the conditions and complications occuring
due to mechanical ventilation.
• Detects all ventilator associated complications, not only
VAP.
• Omission of Chest Xray.
• VAE algorithm is for use in surveillance only.
• Not intended for use in clinical management.
22. VENTILATOR ASSOCIATED CONDITION (VAC)
After 2 days of stability or improvement on the ventilator, the
patient has at least one of the following indicators of
worsening oxygenation:
1) Increase in daily minimum* FiO2 of ≥ 0.20 for ≥ 2
days.
2) Increase in daily minimum* PEEP values of ≥ 3
cmH2O for ≥ 2 days.
23. INFECTION RELATED VENTILATOR ASSOCIATED
COMPLICATION (IVAC)
After at least 3 days of mechanical ventilation and within 2 days of
worsening oxygenation, the patient meets both of the following criteria:
1) Temperature > 38 °C or < 36°C, OR white blood cell count ≥
12,000 cells/mm3 or ≤ 4,000 cells/mm3.
AND
2) A new antimicrobial agent(s) is started, and is continued for ≥
4 days.
Patient meets criteria for VAC
AND
24. POSSIBLE/PROBABLE VAP
After at least 3 days of mechanical ventilation and within
2 days of worsening oxygenation, following criteria are
met : -
Purulent secretions
and/or
Positive culture
Meets criteria for VAC and IVAC
AND
25. POSSIBLE VAP
• Gram stain evidence of
purulent pulmonary
secretions
OR
• Positive pathogenic
pulmonary culture
PROBABLE VAP
• Gram stain evidence of
purulent pulmonary
secretions
AND
• Positive pathogenic
pulmonary culture
28. • Tracheal Aspirate :-
Specimens should be screened by microscopic
examination and discarded if there is evidence of
contamination with mouth secretions.
The presence of more than 10 squamous epithelial cells
per low-power field (× 100) indicates that the specimen
is contaminated with mouth secretions.
The presence of macrophages, regardless of the
number, is evidence that the specimen is from the
lower respiratory tract.
More than 25 neutrophils per low-power field (x 100)
can be used as evidence of infection.
Qualitative culture (sensitivity>90% and specificity≤40%)
Quantitative Culture (sensitivity 76% and specificity 75%)
Quantitative cultures increase specificity of the
diagnosis.
29. • Bronchoalveolar Lavage :-
BAL is performed by wedging the
bronchoscope in a distal airway and performing a
lavage with sterile isotonic saline. A minimum lavage
volume of 120 mL is recommended for adequate
sampling of the lavaged lung segment, and this is
achieved by performing a series of 6 lavages using 20
mL for each lavage.
The lavage fluid is sent to the microbiology lab
for microscopic analysis and quantitative culture.
When intracellular organisms are present in
more than 3% of the cells in the lavage fluid, the
likelihood of pneumonia is over 90%.
30. • BAL Without Bronchoscopy ( Mini- BAL):-
A sheathed catheter is inserted through a tracheal tube
and advanced “blindly” until it wedges in a distal
airway. An absorbable polyethylene plug at the tip of
the catheter prevents contamination while the catheter
is advanced. Once wedged, an inner cannula is
advanced for the BAL, which is performed with 20 mL
of sterile saline.
Only 1 mL of BAL aspirate is required for culture and
microscopic analysis.
Because of the diffuse bilateral nature of VAP and
predominance in dependent lung segments, the yield
from quantitative cultures with mini-BAL is equivalent
to the yield with bronchoscopic BAL.
31. • Protected Specimen Brush :-
Aspiration of secretions through a bronchoscope
produces false-positive cultures because of
contamination as the bronchoscope is advanced
through the tracheal tubes and upper respiratory tract.
To eliminate this problem, a specialized brush
called a protected specimen brush (PSB) is advanced
from the inner cannula to collect samples from the
distal airways.
The multifocal nature of VAP suggests that BAL
and endotracheal aspirates can provide more
representative samples than the protected specimen
brush (PSB), which samples only a single bronchial
segment.
32. Most studies show that the mortality in VAP is not influenced by
the microbiological method used to identify infection, and
this observation is used to support the continued use of tracheal
aspirates in the evaluation of VAP.
Negative lower respiratory tract cultures has a strong negative
predictive value (94%) for VAP and can be used to stop antibiotic
therapy in a patient who has had cultures obtained in the
absence of an antibiotic change in the past 72 hours.
Extrapulmonary site of infection should be searched if there is
sign of infection but negative respiratory cultures.
33. VENTILATOR BUNDLE THERAPY
• Set of procedures to be implemented together.
• Different studies and hospitals have used
different bundle components-
Head end elevation
Oral care with Chlorhexidine
Daily sedation hold & SBT
Stress ulcer prophylaxis
DVT prophylaxis
• Shown to reduce VAP rates.
34. HAND HYGIENE
• Infection control measures: staff education,
Compliance with alcohol-based hand
disinfection, and isolation to reduce cross-
infection with MDR pathogens.
• should be used routinely (Level I).
35. HEAD END ELEVATION
• 30-45 degree
• Decreases risk of
aspiration
• Reduces VAP incidence
• Level I evidence
36. SUBGLOTTIC SUCTIONING
• Specially designed ETT
• Continuous suction -
20cm H2O
• Decreases VAP
• Level I evidence
• Risk- mucosal injury
SUBGLOTTIC
SECRETIONS
37. ORAL HYGIENE
Povidone-iodine, chlorhexidine
• Oral Chlorhexidine : most studied.
• Decreases oropharyngeal colonization.
• Several meta analyses show: reduction of VAP
rates, mainly in cardiac surgery patients.
• Used as a standard measure.
38. SILVER COATED ETT
• Silver : anti-microbial, anti-adhesive properties
• Prevents BIOFILM formation.
• Studies show reduced VAP rates.
• Limitation: it can only delay ETT colonization,
biofilm will eventually form over time as
secretions accumulate.
• NASCENT study: decreased VAP rate, but no
decrease in mortality.
Further studies needed to make a recommendation
39. POLYURETHANE CUFF ETT
• Ultra thin cuffs.
• As compared to PVC cuff, they theoretically
reduce channel formation and micro
aspiration of secretions.
• Data is limited.
• Further trials are needed to evaluate its
efficacy.
43. Management
All patients should have a comprehensive medical history
obtained and undergo physical examination to define the
severity of HAP, to exclude other potential sources of
infection.
All patients should have a chest radiograph to define the
severity of pneumonia (multilobar or not) and the presence
of complications, such as effusions or cavitation .
Arterial oxygenation saturation should be measured in all
patients to determine the need for supplemental oxygen
OR to manage patients who require mechanical
ventilation.
Other laboratory studies (complete blood count, serum
electrolytes, renal and liver function), can point to the
presence of multiple organ dysfunction and thus help
define the severity of illness.
44. Samples of lower respiratory tract secretions e.g. endotracheal
aspirate, bronchoalveolar lavage, or protected specimen
brush sample should be obtained from all patients with
suspected VAP, and should be collected before antibiotic
changes.
A sterile culture of respiratory secretions in the absence of a
new antibiotic in the past 72 hours virtually rules out the
presence of bacterial pneumonia, but viral or Legionella
infection is still possible.
All patients with suspected VAP should have blood cultures
collected, recognizing that a positive result can indicate the
presence of either pneumonia or extrapulmonary infection.
The sensitivity of blood cultures is less than 25%.
A diagnostic thoracentesis to rule out a complicating empyema
or parapneumonic effusion should be performed if the
patient has a large pleural effusion or if the patient with a
pleural effusion appears toxic.
45. Clinical Strategy
The presence of a new or progressive radiographic infiltrate plus at
least two of three clinical features (fever>38C, leukocytosis or
leukopenia, purulent secretions) represents the most accurate
combination of criteria for starting empiric antibiotic therapy.
A reliably performed Gram stain of tracheal aspirates is used to guide
initial empiric antibiotic therapy.
The etiologic cause of pneumonia is defined by semiquantitative
cultures (light, moderate, or heavy) of endotracheal aspirates with
initial microscopic examination.
If a clinical strategy is used, reevaluation of the decision to use
antibiotics based on the results of semiquantitative lower
respiratory tract cultures and serial clinical evaluations, by Day 3 or
sooner, is necessar.y.
Diagnostic techniques that identify etiologic pathogens on the basis of
qualitative cultures leads to therapy for more organisms than
diagnostic techniques based on quantitative cultures.
46. Bacteriological Strategy
The bacteriologic strategy uses quantitative cultures of lower
respiratory secretions (collected with or without a bronchoscope)
to define both the presence of pneumonia and the etiologic
pathogen and can be used to guide antibiotic therapy decisions.
Semiquantitative cultures of tracheal aspirates are not as reliable as
quantitative cultures to define the presence or absence of
pneumonia and the need for antibiotic therapy.
Growth above a threshold concentration is required to diagnose VAP
(separate colonizing from infecting pathogens), and to determine
the causative microorganism(s).
The use of a bronchoscopic bacteriologic strategy has been shown to
reduce 14-day mortality, compared with a clinical strategy, in one
study of suspected VAP.
Patients started on therapy within 24 (and up to 72) hours may have
negative cultures and false negative culture can lead to a failure to
treat either a specific patient or a specific pathogen. Another issue
with the bacteriologic strategy is that culture results are not
available immediately.
53. Delay in the initiation of appropriate antibiotic therapy
for patients with VAP is associated with increased
mortality.
Choice of specific agents should be dictated by local
microbiology, cost, availability, and formulary
restrictions (Level II).
Initial empiric therapy should be adapted to local patterns
of antibiotic resistance, with each ICU collecting this
information and updating it on a regular basis (Level II).
In selecting empiric therapy for patients who have
recently received an antibiotic, an effort should be
made to use an agent from a different antibiotic class,
because recent therapy increases the probability of
inappropriate therapy and can predispose to resistance
to that same class of antibiotics (Level III).
54. Initial therapy should be administered to all patients
intravenously, with a switch to oral/enteral therapy in
selected patients with a good clinical response and a
functioning intestinal tract. Highly bioavailable agents,
such as the quinolones and linezolid, may be easily
switched to oral therapy in such patients (Level II).
Fluoroquinolones and linezolid equal or exceed their
serum concentration in bronchial secretions.
Efforts should be made to shorten the duration of therapy
from the traditional 14 to 21 days to periods as short as
7 days, provided that the etiologic pathogen is not
P. aeruginosa, and that the patient has a good clinical
response with resolution of clinical features of
infection (Level I).
55. • Provided Good clinical response to therapy is
present, use short duration therapy in pts with
VAP without -
• Immunodeficiency
• CF
• Empyema
• Lung abscess
• Cavitation
• Necrotizing pneumonia
Prolonged therapy leads to colonization with
antibiotic resistant bacteria, which may precede a
recurrent episode of VAP.
56. Combination therapy vs Monotherapy
Combination therapy should be used (agents from
different antibiotic classes) if patients are likely to be
infected with MDR pathogens (Level II). No data have
documented the superiority of this approach compared
with monotherapy, except to enhance the likelihood of
initially appropriate empiric therapy (Level I).
Although quinolones can penetrate into the lung better
than aminoglycosides and have less potential for
nephrotoxicity, a trend toward improved survival
has been seen with aminoglycoside-containing
combinations. If patients receive combination therapy
with an aminoglycoside-containing regimen, the
aminoglycoside can be stopped after 5–7 days in
responding patients (Level III).
57. Monotherapy with selected agents can be used for
patients with severe HAP and VAP in the absence of
resistant pathogens (Level I).
Patients in this risk group should initially receive
combination therapy until the results of lower
respiratory tract cultures confirm that organism
grown is not MDR (Level II).
Monotherapy is also the standard when gram-positive
HAP, including MRSA, is documented.
58. Inhaled Antibiotics
• Increase the antibiotic concentration at the site of
infection.
• Useful for organisms with high MIC to systemic antibiotics.
• Penetration is an issue (airflow limitation to diseased lung).
• May be inactivated by sputum.
• May trigger cough, bronchospasm (induced by the
antibiotic or the associated diluents).
• Colistin methanesulfonate (CMS): better tolerated.
• Dose: 1-2 mIU, 3 or 4 times a day.
Aerosolized antibiotics have not been proven to have value in
the therapy of VAP (Level I). However, an inhaled
aminoglycoside or polymyxin may be considered as
adjunctive therapy in patients with MDR gram-negatives who
are not responding to systemic therapy (Level III).
59. Specific Antibiotic Regimens
If P. aeruginosa pneumonia is documented, combination
therapy is recommended. The principal justification is
the high frequency of development of resistance on
monotherapy. Although combination therapy will not
necessarily prevent the development of resistance,
combination therapy is more likely to avoid
inappropriate and ineffective treatment of patients
(Level II).
If Acinetobacter species are documented to be present,
the most active agents are the carbapenems,
sulbactam, colistin, and polymyxin. There are no data
documenting an improved outcome if these organisms
are treated with a combination regimen (Level II).
60. If ESBL + Enterobacteriaceae are isolated, then
monotherapy with a third-generation
cephalosporin should be avoided. The most
active agents are the carbapenems (Level II).
If L. pneumophila is suspected, the combination
antibiotic regimen should include a macrolide
(e.g., azithromycin) or a fluoroquinolone (e.g.,
ciprofloxacin or levofloxacin) rather than an
aminoglycoside.
Linezolid is an alternative to vancomycin for the
treatment of MRSA VAP and may be preferred on
the basis of a subset analysis of two prospective
randomized trials (Level II). This agent may also
be preferred if patients have renal insufficiency or
are receiving other nephrotoxic agents.
61. Response To Therapy
A serial assessment of clinical parameters should be used to
define the response to initial empiric therapy (Level II).
Modifications of empiric therapy should be made on the
basis of this information, in conjunction with microbiologic
data (Level III).
Clinical improvement usually takes 48–72 hours, and thus
therapy should not be changed during this time unless
there is rapid clinical decline (Level III). Nonresponse to
therapy is usually evident by Day 3, using an assessment of
clinical parameters (Level II).
Serial quantitative microbiologic studies of lower respiratory
tract secretions can also define resolution end points.
62. In HAP/VAP, bedside clinical assessment vs serial biomarkers
to predict adverse outcomes/clinical response at 72-96 hrs
• Routine measurement of biomarkers (CRP, Procal, Copeptin,
MR pro ANP) in addition to bedside clinical assessment is
not recommended. {strong reco}
• Clinical assessment-
1. Temp
2. Tracheobronchial secretions
3. Culture and purulence assessment of secretions
4. TLC
5. CXR resolution
6. P/F ratio
7. Scores- CPIS, SOFA
63. Chest radiographs are of limited value for defining clinical
improvement in severe pneumonia, and initial
radiographic deterioration is common, especially
among patients who are bacteremic or who are
infected with highly virulent organisms. In addition,
radiographic improvement often lags behind clinical
parameters.
However, the finding of a rapidly deteriorating
radiographic pattern, with a follow-up chest radiograph
showing progression to multilobar involvement, a
greater than 50% increase in the size of the infiltrate
within 48 hours, development of cavitary disease, or
significant pleural effusion, should raise concern.
64. Improvement in the CPIS occurring during the first 3
days of empiric treatment was associated with
hospital survival whereas a lack of improvement in
the CPIS predicted mortality.
The responding patient should have de-escalation of
antibiotics, narrowing therapy to the most focused
regimen possible on the basis of culture data. Also,
when the organism isolated is sensitive to a less
broad-spectrum antibiotic than the antibiotic used
in the initial regimen. (Level II).
65. The nonresponding patient should be evaluated for
unsuspected or drug-resistant organisms, non-infectious
mimics of pneumonia, extrapulmonary sites of infection, and
complications of pneumonia and its therapy. Diagnostic
testing should be directed to whichever of these causes is
likely (Level III).
