DR.T.V.RAO MD
Ventilator-Associated
Pneumonias (VAP)
Pneumonia can be a life threatening condition
Nosocomial pneumonia (NP), hospital-acquired pneumonia (HAP) and 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 Associated Pneumonia (VAP)
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 Pneumonia (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.
;
Challenge and Controversy
The diagnosis and management of VAP remains one of the most controversial and challenging topics in management of critically ill patients.”
Centres for Disease and Control
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)
7
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
Mechanical ventilation 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
Nosocomial infection are Multidrug 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
Definition– Ventilator Associate Pneumonia
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.
Prevalence of VAP
Occurs in 10-20% of those receiving mechanical ventilation for greater than 48 hours
Rate= 14.8 cases per 1000 ventilator days
When 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 pneumoniain critically ill patients.
Time frame 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 .
Who gets VAP? (Risk 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
PAHOGENESIS The pathogenesis of
ventilator-associated pneumonia usually requires that two important processes take place: Bacterial colonization
of the aero digestive tract
The aspiration of contaminated secretions into the lower airway.
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
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
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
Common and Uncommon isolates in VAP
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
Drug resistance a concern in Ventilator Associated
Pneumonias A. baumanni was the most common isolated pathogen many of them were multidrug-resistant (MDR) or pan drug-resistant (PDR). The other common isolated pathogens were K. pneumoniae, P. aeruginosa and methicillin-resistant S. aureus (MRSA).
23
Other Isolates in Ventilator associated Pneumonias
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 Citrobacter and Serratia species
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
26
Staphylococcus aureus and Streptococcus pneumoniae
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
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
Influenza too can cause VAP
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
Fungal pathogens can cause VAP
Fungal pathogens.Aspergillus 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 cuff
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
Am J Resp Crit Care (1995)
Oropharyngeal colonization can be
source of VAP Scannapieco et al showed 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)
Gastrointestinal 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 effective strategies for prevention
Viral 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 viral cases of HAP,VAP, and HCAP
Multidrug resistant organisms are associated with …
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
Supine 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 Biofilm formation
Exopolysaccharide outer layer with quiescent bacteria within Difficult for bacteria
to penetrate outer layer and bacteria within resistant to bactericidal effects of bacteria
Difficult to kill biofilm organisms
Comparison of MBC of antibiotics for tracheal isolates vs. biofilm isolatesOrganism Tobramycin Cefotaxime Cefuroxime
P. aeruginosa-Tracheal-ET
256>1024
32>1024
>1024>1024
Enterobacteriaceae-Tracheal-ET
4>1024
128256
32512
S. aureus-Tracheal-ET
18>1024
16128
16>1024
41
Clinical Strategy in Diagnosis of VAP
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.
Pathogens in VAP (1)
Pathogens that cause VAP differ depending on whether the condition occurs early (less than 96 hours after intubation or admission to ICU) or late (greater than 96 hours after intubation or admission to ICU)
Pathogens in VAP (2)
Early–Onset 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 ???
Diagnosis is imprecise and usually based on a Combination
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 Diagnosis in VAP are multifaceted
Clinical Strategy
Bacteriologic 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%
Gram 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
Specimen collection for Optimal Results
Distal airway samples may be obtained by using bronchoscopic or nonbronchoscopic techniques. With nonbronchoscopic 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/plate2+: few 10-102 colonies/plate3+: moderate >102-3 colonies/plate4+: numerous >103-4 colonies/plate5+: numerous >104 colonies/plate
Tracheal aspirates are valuable specimens
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 in-flammatory 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
Collection of bronchial Secretions
Distal airway samples may be obtained by using bronchoscopic or nonbronchoscopic techniques. With nonbronchoscopic 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.
Qualitative and quantitative
Qualitative endotracheal aspirates are easy to obtain but have a high false-positive rate in ICU patients because of airway colonization. When quantitative endotracheal-aspirate cultures are used, a cutoff value of 106 is the most accurate, with a sensitivity of 38-82% and a specificity of 72-85%
False negative – False Positive Results
Investigators reported that the clinical diagnosis of VAP is associated 30–35% 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)
Other Supporting Bacterial Cultures
Bacteraemia and positive pleural effusion 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 > 10 mm, even though spread to the blood or pleural space occurs in < 10% of VAP
Multiresistant pathogens in Ventilator associated
pneumonias 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
Uncommon microbes are often missed
Legionella species , 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
61
Comparing Diagnostic 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
Microbiologists / Physicians should consider other Diagnostic
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/FiO2- and semi quantitative culture of tracheal aspirate) for the diagnosis of VAP, defined as clinical pulmonary infection score (CPIS)
Mortality
Appropriate Mortality
Inappropriate Mortality
Early Mortality
Evidence-based early and appropriate therapy in VAP
Best option in choosing Antibiotics
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
Continuous Removal of Subglottic Secretions
Use an ET tube with continuous suction through a dorsal lumen above the cuff to prevent drainage accumulation
Use an ET tube with continuous suction through a dorsal lumen above the cuff to prevent drainage accumulation
HOB ElevationHOB Elevation
HOB at 30-45o
Keep the HOB elevated to at least 30 degrees unless medically contraindicated
HOB at 30-45o
Keep the HOB elevated to at least 30 degrees unless medically contraindicated
Condensate management Heat-moisture exchanger
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
secretionsCDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.
Condensate management
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 patient
HandwashingHandwashing
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.
Epidemiological data differs 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 with VAP is complex
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.
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