CONTENTS
- Stepwise approach to VAP
- Step #1 – Does the patient have probable VAP?
- Step #3 – Management of suspected VAP
- #3b) Antibiotics for probable VAP
- Step #5 – Management of confirmed VAP
- #5a) Deescalate antibiotics
- #5b) Duration of therapy
- Treatment failure
- Differential diagnosis
- Ancillary topics
- Bronchoscopy
- The riddle of VAP
- VAP prevention
- Podcast
- Pitfalls
step #1 – consider rapidly available information
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step #1 – consider rapidly available information
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There are roughly four sources of clinical information that should be rapidly available when considering the possibility of VAP. Try to consider all evidence rather than anchoring on a single bit of evidence.
(a) evidence of inflammation
- Leukocytosis: (32306086)
- Sensitivity ~64%, specificity ~59%.
- Positive likelihood ratio 1.6; negative likelihood ratio(-LR) of 0.6
- Left-shift, neutrophil/lymphocyte ratio.
- Fever: (32306086)
- Sensitivity 66%; specificity 54%.
- Positive likelihood ratio 1.4; negative likelihood ratio LR 0.6
- Hypothermia.
- Septic shock.
(b) evidence of pulmonary dysfunction
- Secretions:
- Purulent secretions (sensitivity 77%; specificity 39%; +LR 1.3; -LR 0.6). (32306086)
- Increased secretion volume.
- Worsening oxygenation (a requirement for higher FiO2 and/or PEEP).
(c) radiographic evidence
- Chest radiograph
- Infiltrate on chest radiography is fairly sensitive (89%) but nonspecific (26%). Consequently, the +LR is 1.2, and the -LR is 0.4. (32306086)
- Imperfect sensitivity is due partially to portable films that often miss opacities hiding behind the heart or diaphragms.Detecting a new infiltrate is even harder among patients with pre-existing radiographic abnormalities (e.g., ARDS).
- Poor specificity is the major problem with chest radiography. Opacities may also represent atelectasis, aspiration pneumonitis, pulmonary infarction, chronic pulmonary fibrosis, or cardiogenic pulmonary edema.
- Repeat radiographs may sometimes help clarify the diagnosis. True pneumonia will resolve very slowly, whereas atelectasis or aspiration will often resolve within 1-2 days.
- CT scan:
- This remains the gold-standard imaging study for thoracic infection. CT scan is superior to chest radiography in differentiating between atelectasis and pneumonia. The main drawback of CT scanning is the logistic challenge of transporting the patient to the CT scanner.
- The sensitivity of the CT scan is ~100%: the absence of an infiltrate on the CT scan excludes pneumonia.
- The specificity of CT scans is variable, depending on the specific findings. CT scan is exquisitely sensitive for mild opacities, so the presence of an opacity may be nonspecific. As with any radiologic study, review the images yourself and compare them to prior studies (radiologists may err on the side of safety by overcalling “possible pneumonia”).
(d) alternative diagnostic considerations
- It's essential to avoid falling into the trap of anchoring on a binary diagnostic approach (e.g., does the patient have VAP – yes or no?). A better approach is to consider the broader question: what process does the patient have? If an alternative diagnosis is established, this makes VAP far less likely.
- Some prominent differential diagnostic possibilities are listed below. 📖
step #2 – when to pull the trigger on antibiotics and cultures
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step #2 – when to pull the trigger on antibiotics and cultures
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a clinical decision is required
- If VAP is considered likely, then cultures should be sent and antibiotics initiated.
- If VAP is considered unlikely, then neither cultures nor antibiotics are indicated.
- ⚠️ Cultures will often be positive among intubated patients, so obtaining cultures without suspicion of infection should be avoided. This may lead to false-positive cultures and unnecessary antibiotic therapy.
- Additional courses of action which may be contemplated include:(32306086)
- Attempt to treat other problems (e.g., diuresis or ventilator strategies to improve lung recruitment).
- Chest CT scan to more clearly define the disease process.
- Bronchoscopy (this could be appropriate for patients with significant immunosuppression or if there is a concern regarding diffuse alveolar hemorrhage).
there are no validated criteria for this decision
- Previously, the Clinical Pulmonary Infection Score (CPIS) was used to adjudicate the diagnosis of VAP.Unfortunately, meta-analysis demonstrated that the Clinical Pulmonary Infection Scoredoesn't have adequate performance, so it is no longer recommended.(32306086)
step #3a – management of suspected VAP – cultures & repeat imaging
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step #3a – management of suspected VAP – cultures & repeat imaging
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additional diagnostic studies for a patient with suspected VAP
- (1) Blood cultures (two peripheral cultures, plus cultures of any central line in place >72 hours).
- (2) Tracheal aspirate for gram stain and culture.
- (3) PCR studies for relevant respiratory viruses (e.g., influenza, COVID-19, RSV).
- Hospital-acquired viral pneumonia isn't common, but it absolutely can happen.
- (4) Nasal PCR for MRSA (if not recently performed).
- (5) Procalcitonin levels (for patients without severe immune compromise).
- (6) Additional radiologic data:
- A repeat chest X-ray after 24-48 hours may be helpful.
- A chest CT scan may be helpful (especially if chest X-ray images are equivocal).
- (7) Consider evaluation for invasive Aspergillus 📖
- Potential indications (more detail in below table):
- Prolonged ARDS due to influenza or COVID-19.
- Prolonged neutropenia.
- Prolonged steroid use.
- Organ transplantation.
- An investigation may include:
- CT scan.
- Serum galactomannan antigen and beta-D-glucan.
- Bronchoalveolar lavage for culture & fungal stain, PCR, and galactomannan.
- Potential indications (more detail in below table):
step #3b – management of suspected VAP – antibiotics
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step #3b – management of suspected VAP – antibiotics
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early-onset VAP (within <5 days of admission) is treated similarly to community-acquired pneumonia (CAP)
- Patients who have been admitted for <5 days generally haven't yet been colonized with nosocomial organisms. They may be treated with the same antibiotic regimen that would have been used if they were admitted to the hospital with community-acquired pneumonia.
- A common CAP regimen would be a combination of ceftriaxone 💉 plus azithromycin 💉. However, broader coverage may be required depending on individual patient risk factors.
- Further discussion of antibiotic therapy for CAP is here: 📖
late-onset VAP (>5 days after hospital admission) requires an empiric antibiotic regimen directed at VAP
[#1/2] Backbone agent: Antipseudomonal beta-lactam
- This is generally cefepime or piperacillin/tazobactam (comparison here: 📖).
- Meropenem may occasionally be considered if there is a concern for an extended-spectrum beta-lactamase resistance organism (ESBL).
- Ceftazidime is a poor choice, given poor gram-positive coverage (discussion: 📖).
- For patients with recent antibiotic exposure, an agent they weren't exposed to is sensible.
- Prior microbiologic data should be reviewed.
- Double coverage of pseudomonas isn't generally evidence-based and may increase toxicity. 🌊 In units with exceptionally high rates of multidrug-resistant bacteria, broader empiric therapy may be considered.
[#2/2] MRSA coverage?
- Not all patients with VAP require MRSA coverage.
- Only ~40% of patients with suspected VAP will end up truly having a genuine VAP. MRSA is the cause of only ~10-20% of VAP infections. (28902529, 29340593) Consequently, only ~5% of patients with suspected VAP may have a true MRSA VAP infection. Depending on individual risk factors, this may or may not be worth covering empirically.
- MRSA VAP is probably substantially over-diagnoseddue to difficulties sorting out colonization versus invasive infection (with a tendency to err towards treatment).
- General indications for considering MRSA coverage are listed below.(based on IDSA guidelines, 27418577) These criteria are sensitive, but not specific:(28902529)
- Receipt of intravenous antibiotics within the last 90 days.
- Longer duration of hospitalization before the occurrence of VAP.
- Hospitalized in a unit where >20% of Staph aureus isolates are MRSA.
- Patients at high mortality risk (e.g., septic shock).
- Known colonization with MRSA.
- MRSA coverage isn't necessary for patients with a negative nares PCR.(33004324, 29340593)
- Nares PCR is only ~70% sensitive for MRSA, so this doesn't entirely exclude the diagnosis of MRSA pneumonia. However, for patients at an average risk of MRSA (e.g., ~5% likelihood), a negative nares PCR reduces the likelihood of MRSA to <2%. At this level, antibiotic toxicity risk likely overshadows antibiotic therapy's benefits.
- In ICUs with extraordinarily high rates of MRSA, MRSA coverage may be considered even among patients with a negative nares PCR.
- If MRSA coverage is indicated, this is generally achieved with linezolid or vancomycin.
- Given superior pulmonary penetration and more predictable pharmacokinetics, linezolid may be superior to vancomycin for treating MRSA VAP. One RCT found that linezolid led to improved clinical resolution and less nephrotoxicity compared to vancomycin. (22247123) More on vancomycin versus linezolid: 📖
(atypical coverage is usually not indicated)
- Atypical bacteria (e.g., Mycoplasma, Chlamydiae, Legionella) don't generally cause VAP. Consequently, atypical coverage is generally not utilized.
- If your hospital water system is known to harbor Legionella, add coverage (e.g., azithromycin) and obtain a Legionella urinary antigen test.
(anaerobic coverage is not indicated)
- Anaerobic coverage for pulmonary infections is generally indicated only in the context of empyema or lung abscess.
step #4 – data review & diagnosis adjudication
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See AlsoKukohoa kwa Watoto - Kukohoa kwa Watoto - Toleo la Mtumiaji la Mwongozo wa MSDHospital-Acquired Pneumonia - Hospital-Acquired Pneumonia - Merck Manual Consumer VersionNimonia ya Mpumuo na Nimonia ya Kemikali - Nimonia ya Mpumuo na Nimonia ya Kemikali - Toleo la Mtumiaji la Mwongozo wa MSDBacterial Pneumonia: Practice Essentials, Background, Pathophysiology
step #4 – data review & diagnosis adjudication
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Among patients who are started on antibiotics for VAP, only ~40-50% are eventually diagnosed with it after all the data is available. (18091545, 31754887) Therefore, it's essential to re-consider the diagnosis as additional information becomes available. If emerging evidence is inconsistent with a diagnosis of pneumonia, antibiotics should be discontinued, and the diagnosis should be discarded.
tracheal aspirate gram stain & culture
- Tracheal sampling basics:
- Unlike community-acquired pneumonia, VAP is almost always due to gram-positive or gram-negative organisms that can be cultured in the microbiology lab. Additionally, compared to community-acquired pneumonia, VAP is more likely to represent bronchopneumonia (rather than lobar pneumonia) – which is more amenable to sputum sampling (more on types of pneumonia: 🌊).
- Bronchoscopic or quantitative culture methods are generally unnecessary. Qualitative tracheal aspirates are cheaper, easier, and more sensitive. (More on the role of bronchoscopy below 📖)
- Gram stain interpretation
- If the gram stain shows no evidence of inflammation (i.e., no leukocytes) – this strongly argues against a diagnosis of VAP.
- Suppose the gram stain is ofhigh quality (e.g., <10 squamous epithelial cells and >25 neutrophils per high power field), and it shows asingle dominant bacterial morphology (e.g., gram-positive cocci or gram-negative rods). In that case, this is likely reliable information that can be used to adjust antibiotic selection.
- If the gram stain shows multiple different organisms, this is nonspecific and cannot be relied upon to modify therapy.
- Interpretation of negative culture result
- If cultures don't grow a pathogenic bacteria associated with VAP, this strongly argues against a diagnosis of VAP (unless antibiotics were initiated before cultures were obtained).
- Interpretation of positive culture result
- Positive cultures from a tracheal aspirate alone don't prove the presence of pneumonia (e.g., they may result from colonization rather than infection).
- Certain species may be more likely to represent colonization than invasive infection: Enterobacter, Proteus, Citrobacter, Flavobacterium, Stenotrophomonas, Burkholderia, and Enterococcus. (Cunha)
blood cultures
- Blood culture data in patients with suspected VAP:
- 15% of patients with VAP will have positive blood cultures.
- Up to 25% of patients with suspected VAP will have positive blood cultures originating from a nonpulmonary source (e.g., line infection).
- If blood cultures are positive, be thoughtful about looking for a nonpulmonary infection – especially if blood cultures reveal an organism that doesn't usually cause pneumonia (e.g., Candida, Enterococcus). (33004324)
additional imaging
- Repeat chest X-ray:
- A repeat chest X-ray after 1-2 days may be helpful.
- If infiltrates rapidly disappear, this suggests atelectasis or aspiration pneumonitis (rather than pneumonia). In true pneumonia, infiltrates take many days to weeks to resolve.
- Stable or worsening infiltrates may support a pneumonia diagnosis.
- Chest CT scan:
- CT scan may be indicated if there is suspicion of pulmonary embolism, fungal pneumonia, or interstitial lung disease.
- A CT scan can also help differentiate between more common entities (e.g., pneumonia vs. atelectasis vs. heart failure).
procalcitonin
- Procalcitonin may be helpful among patients who are not immunosuppressed.
- A procalcitonin value of <<0.5 argues strongly against VAP. This should prompt consideration of discontinuing antibiotics, even if the sputum cultures are positive (positive sputum cultures with a negative procalcitonin may represent colonization rather than infection).
step #5a – antibiotic deescalation
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step #5a – antibiotic deescalation
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For patients with a confirmed diagnosis of VAP, microbiological data should be reviewed to adjust the antibiotic regimen.
MRSA coverage
- MRSA is typically easy to grow in culture (MRSA pneumonia produces lots of sputum and doesn't sterilize rapidly following therapy).
- 🛑 Do not continue MRSA coverage for >48 hours unless there is some evidence of MRSA.
- Nares PCR negative for MRSA suggests that MRSA coverage can be discontinued.
- The absence of MRSA growth in tracheal aspirates is conclusive evidence that MRSA coverage should be discontinued.
if an organism is detected
- Ideally, a causative bacteria will be identified.
- Antibiotic therapies should be tailored for that organism (with discontinuation of unnecessary antibiotics).
if no organism is detected
- Sometimes, no pathogenic organism is detected. If this is the case, the VAP diagnosis should probably be discarded. However, in some situations, VAP can occur without an organism being cultured from the sputum:
- i) Antibiotics were initiated before sputum culture.
- ii) Early-onset VAP leading to infection with atypical or fastidious organisms (e.g., Pneumococcus or Legionella).
- If the concern for VAP remains high despite negative cultures, it may be reasonable to continue antibiotics. However, if cultures have been negative, antibiotic therapy can generally be narrowed down (e.g., to ceftriaxone).
step #5b – duration of therapy
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step #5b – duration of therapy
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- The IDSA/ATS guidelines generally recommend a seven-day course of antibiotics (even for Pseudomonas). (27418577)
- Potential indications for prolonged therapy: (32157357, 30601179)
- Empyema.
- Lung abscess, necrotizing pneumonia.
- Bacteremia with certain gram-positive organisms (e.g., Staph. aureus).
- Severe immunodeficiency (e.g., ongoing neutropenia).
- Bronchiectasis (e.g., cystic fibrosis).
- Procalcitonin may occasionally be helpful to shorten the duration of therapy:
- Procalcitonin levels falling below 20% of the initial value or <<0.25 ng/ml suggest that it is safe to discontinue antibiotics (if this also seems clinically reasonable).
treatment failure
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treatment failure
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The causes and investigation of treatment failure are similar to community-acquired pneumonia: 📖
differential diagnosis
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differential diagnosis
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pulmonary process causing opacities & inflammation
- Aspiration pneumonitis.
- Pulmonary embolism with infarction.
- Fibroproliferative ARDS (persistent fevers can last for days in the remodeling/subacute phase of ARDS).
- Cryptogenic organizing pneumonia (COP).
- Empyema.
- Medication-induced pneumonitis.
the combination of two processes
- #1 = Pulmonary process that doesn't cause inflammation:
- Atelectasis/mucus plugging.
- Asymmetric pulmonary edema.
- Transudative pleural effusion.
- #2 = Extra-pulmonary inflammatory process, e.g.:
- Line infection.
- C. difficile.
- Drug fever.
- Wound infection.
For a more detailed differential diagnosis, see the differential diagnosis of community-acquired pneumonia: 📖.
bronchoscopy
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bronchoscopy
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why bronchoscopy isn't generally indicated to investigate for VAP
- Bronchoscopy hasn't been shown to affect mortality or length of stay in VAP. (25354013) Consequently, routine bronchoscopy is not recommended by the IDSA/ATS guidelines. (27418577)
- Bronchoscopy with protected specimen brush and quantitative culture has only a 61% sensitivity and 77% specificity (for a positive likelihood ratio of 2.6 and a negative likelihood ratio of 0.5). (32306086) Clinicians may overestimate the value of hard-earned bronchoscopic data, leading to misdiagnosis.
- Bronchoscopy may lead to delays in therapy if antibiotics are delayed until a bronchoscopy can be performed.
- Bronchoscopy is an invasive procedure that exposes patients to risks of sedation and desaturation (due to saline instillation).
- Blind mini-BAL involves blindly inserting a catheter into the lungs until it wedges in a terminal bronchus, then performing a bronchoalveolar lavage. Compared to bronchoscopy, this provides less diagnostic information (e.g., no inspection of the bronchial tree or directed aspiration).
when bronchoscopy is indicated
- Bronchoscopy may be indicated when there is a concern for Pneumocystis pneumonia or invasive Aspergillus. Among these, Aspergillus is the primary concern as a nosocomial pathogen causing pneumonia.
- More on Pneumocystis pneumonia.
- More on invasive pulmonary aspergillosis.
- If sampling is required, bronchoscopy is superior to mini-BAL for the following reasons:
- Visualization of the mucosae is possible to evaluate for tracheal aspergillosis.
- It's possible to target areas of the lung that are involved.
- If bronchoscopy is performed, a differential cell count should be obtained. If <50% of the cells are neutrophils, this probably excludes pneumonia.
the riddle of VAP
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the riddle of VAP
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Ventilator-associated pneumonia (VAP) is pneumonia occurring more than >48 hours after intubation. Clinicians must walk several fine lines regarding VAP:
- Undertreatment versus overtreatment:
- Undertreatment: Overlooking the diagnosis until the patient develops septic shock.
- Overtreatment: Treating every patient with possible VAP using numerous broad-spectrum antibiotics.
- Underinvestigation versus overinvestigation
- Underinvestigation: Assuming the diagnosis of VAP without any sophisticated studies.
- Overinvestigation: Broad use of bronchoscopy and CT scan for every patient with a pulmonary infiltrate.
This is not easy. Studies consistently show that among patients who are clinically diagnosed with VAP, only ~40-50% will eventually be found to have VAP (based on microbiological studies). Likewise, all of the early diagnostic indicators of VAP have poor test performance (e.g., fever, leukocytosis, sputum production, and chest radiograph). Consequently, we are doomed to often be wrong when we make the initial diagnosis of VAP. To make matters even more complicated, VAP may have a significant attributable mortality (perhaps ~10%) – so we do need to take it seriously and treat it appropriately.
The fact that our clinical diagnosis of VAP will often be wrong should lead to some restraint regarding the initial antibiotic regimen. Specifically, if the patient probably doesn't have VAP, then it's unwise to unleash a toxic cocktail of vancomycin, cefepime, and an aminoglycoside. The probability of harming the kidneys with these antibiotics is substantial, whereas the probability of randomly hitting a multidrug-resistant pathogen may be lower.
To make the topic even more confusing, there is no gold-standard diagnostic study for VAP (other than autopsy – which isn't a desirable approach). Nearly all tests available have only intermediate performance. Consequently, diagnosing VAP with 100% certainty in clinical practice is usually impossible.
Given these uncertainties, it should come as little surprise that guidelines disagree about approaching the diagnosis and treatment of VAP. European and American guidelines disagree substantially regarding the use of bronchoscopy and the selection of empiric antibiotic regimens. (30601179, 30063491, 30390750) These disagreements don't imply that either guideline is wrong but rather that the optimal approach to VAP remains unknown. Numerous reasonable approaches exist. The approaches explored below are more consistent with American guidelines.
Ultimately, where does this leave us? In a place of diagnostic and therapeutic humility. We must recognize that our clinical acumen will frequently fail us. Consequently, we must continuously re-evaluate the data and reconsider our provisional diagnoses. Likewise, our initial therapies will frequently be suboptimal, requiring ongoing revision.
Mirroring the uncertainty surrounding VAP, our approach to it is a stepwise and recursive process. Let's walk through these steps…
VAP prevention
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VAP prevention
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- Avoidance of intubation when possible (e.g., using noninvasive ventilation).
- Orogastric tubes should be used rather than nasogastric tubes (the latter tend to cause sinusitis and increase the risk for VAP).
- Aggressive weaning off mechanical ventilation.
- Conservative blood transfusion policy (transfusion is a risk factor for VAP).
- Avoidance of very high (pulse-dose) steroids when possible, as this may increase the risk of nosocomial Aspergillus pneumonia.
- VAP prophylaxis:
- PROPHY-VAP trial: a one-time dose of 2 grams of ceftriaxone was beneficial for patients intubated with severe brain injury and anticipated duration of intubation >48 hours. (38262428)
- ANTARCTIC trial: two days of therapy with ampicillin-sulbactam following intubation for cardiac arrest reduced the risk of VAP with a trend towards reduced time on mechanical ventilation. (31693806)
podcast
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questions & discussion
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questions & discussion
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To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Continuation of MRSA coverage >48 hours despite zero evidence that the patient has MRSA pneumonia.
- Use of fluoroquinolones for VAP (they have no role, as explained here, here, and especially here).
- Failure to re-evaluate all data 24-48 hours after starting antibiotics. Remember, ~50% of patients started on antibiotics will ultimately not be diagnosed with VAP.
Guide to emoji hyperlinks
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- = Link to IBCC section about a drug.
- = Link to IBCC section covering that topic.
- = Link to FOAMed site with related information.
- = Link to supplemental media.
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