Table of Contents
Credits
Hosts: Sam Schuiteman, Sara Dong
Guest: Owen Albin
Writing: Sam Schuiteman, Sara Dong
Producing/Editing/Cover Art/Infographics: Sara Dong
Our Guests
Guest Co-Host
Sam Schuiteman, MD
Dr. Sam Schuiteman is a PGY-2 resident in Internal Medicine at the University of Michigan, where he also completed medical school.
Guest Discussant
Owen Albin, MD
Dr. Owen Albin is an Assistant Professor of Internal Medicine in the Division of Infectious Diseases at the University of Michigan Medical School in Ann Arbor, MI. He also completed his medical school, residency, and ID fellowship training at the University of Michigan
Culture
Sam shared that he has been cooking a lot with Alison Roman recipes, such as shrimp scampi! Check out some recipes here
Owen shared Kenji Alt-Lopez’s The Wok Book as well as the children’s book Every Night is Pizza Night!
Consult Notes
Consult Q
diagnosis and management of VAP
Key Points
The HAI School Series! HAI = Healthcare Acquired Infections
This episode is #4 of 4 in another Febrile series, this time entitled “HAI School”! This bundle of episodes will discuss some healthcare associated infections (CLABSI, CAUTI, SSI, and VAP). Check out all four episodes (#60-63) to hear them all! The first three are from a team from Beaumont Health, and the fourth episodes features a team from the University of Michigan
Let’s start with the basics! What is ventilator associated pneumonia (VAP)? How common is it?
- VAP is a type of hospital acquired pneumonia that develops in patients who have been intubated for >=48 hrs or within 48 hrs of extubation
- VAP prevalence in patients who require invasive mechanical ventilation >48 hrs is generally about 5-20%
- There are patients who are at higher risk (such as ARDS, ECMO, COPD, trauma, intracranial bleeds), who might have prevalence closer to 30-40%
- To check on the latest data, you can access some info at the CDC website, such as:
- Current National and State HAI Progress Report, where data tables and summaries are available
- National and State Factsheets are available at the Antibiotic Resistance & Patient Safety Portal
What are the risk factors for VAP?
Owen grouped the risk factors for VAP into three buckets:
- Duration of mechanical ventilation! The risk rises with each day of intubation, peaking around day 5
- Aspiration risk: reintubation, impaired consciousness, supine positioning
- Colonization in the gut or oropharynx: H2 blockers, prior antibiotic use
What is the pathophysiology of VAP?
- Owen explained how almost all pneumonia is fundamentally aspiration pneumonia:
- The primary route of infection is microaspiration of organisms that colonize the oropharyngeal tract and gastrointestinal tract: You get colonized with organisms, probably in your stomach, which move up into the oropharynx, establishes a biofilm on the endotracheal tube
- Then as host defenses in the lung are impaired (because of sedation, etc), it is easier to achieve sufficient volume or bioburden of organisms in endotracheal tube to make it’s way into the alveolar space
- From there, the host immune system responds and causes pneumonia
- Additional links:
- Here is the link to the series of institutional VAP cases traced back to contaminated green food coloring in hospital food: File TM Jr, Tan JS, Thomson RB Jr, Stephens C, Thompson P. An outbreak of Pseudomonas aeruginosa ventilator-associated respiratory infections due to contaminated food coloring dye–further evidence of the significance of gastric colonization preceding nosocomial pneumonia. Infect Control Hosp Epidemiol. 1995;16(7):417-418. doi:10.1086/647141
- Garrouste-Orgeas M, Chevret S, Arlet G, et al. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. Am J Respir Crit Care Med. 1997;156(5):1647-1655. doi:10.1164/ajrccm.156.5.96-04076
What are some of the challenges of diagnosing VAP?
- VAP is a challenging diagnosis to make. There is no good confirmatory test and the diagnosis is based on an amalgamation of nonspecific clinical, radiographic, and microbiologic symptoms and signs. None of which perform very well when you use autopsy based histopathology as the reference gold standard. In addition, the costs of missing the diagnosis are high.
- Owen discussed that overdiagnosis of VAP is OK in many situations. Given considerable morbidity, inherent diagnostic ambiguity, and clinically tenuous nature of patients most at risk for acquiring VAP, presumed diagnosis and treatment are often warranted
- That said, there is growing evidence that we’re really overdoing it:
- Discharge diagnoses of pneumonia have been rising significantly in the last few decades, a trend not seen for the 10 other most common causes of hospitalization
- Multidisciplinary case reviews (involving ID and surgical and medical intensivists) show that 59-76% of cases diagnosed as ventilator-associated pneumonia do not meet diagnostic criteria
- A recent study of over 12000 hospitalized patients diagnosed with “pneumonia” found that 20% lack ANY cardinal signs/or symptoms of the illness
- One contributing component of this overdiagnosis is likely the equation of positive respiratory cultures = infection, but a positive culture from the respiratory tract is not synonymous with infection.
- Check out this commentary from Owen on using “asymptomatic bacterisputia” to rethink diagnostic stewardship in pneumonia: Albin OR, Pogue JM, Petty LA, Kaye KS. Asymptomatic bacterisputia: Rethinking diagnostic stewardship in pneumonia. Infect Control Hosp Epidemiol. 2021;42(6):737-739. doi:10.1017/ice.2021.109
- Asymptomatic bacterisputia is common! 25% of hospitalized patients, 50% of ICU patients, up to 90% of patients with tracheostomy
- But it is a nonspecific finding and requires clinical correlation
- Think of this like asymptomatic bacteruria. Like ASB, we know that this is common and that recovery of organisms is not synonymous with infection – but we do NOT have good diagnostic stewardship approaches to this problem!
- Some additional references:
- Here is a study of 1290 adult patients with positive respiratory cultures and minimal ventilatory settings (PEEP<5, FiO2<40%). No significant differences in propensity-matched cohort for ventilator death, time to hospital discharge alive, in-hospital death, or time to extubation alive.
- Klompas M, Li L, Menchaca JT, Gruber S; Centers for Disease Control and Prevention Epicenters Program. Ultra-Short-Course Antibiotics for Patients With Suspected Ventilator-Associated Pneumonia but Minimal and Stable Ventilator Settings. Clin Infect Dis. 2017;64(7):870-876. doi:10.1093/cid/ciw870
- There is confounding by indication in this study, but Owen’s takeaway is that either some patients with VAP can be treated with exceedingly short courses of antibiotics OR that some patients diagnosed with VAP based on positive respiratory cultures did not require antibiotics in the first place
- Tejerina E, Esteban A, Fernández-Segoviano P, et al. Accuracy of clinical definitions of ventilator-associated pneumonia: comparison with autopsy findings. J Crit Care. 2010;25(1):62-68. doi:10.1016/j.jcrc.2009.05.008
- Here is a study of 1290 adult patients with positive respiratory cultures and minimal ventilatory settings (PEEP<5, FiO2<40%). No significant differences in propensity-matched cohort for ventilator death, time to hospital discharge alive, in-hospital death, or time to extubation alive.
So how do we diagnose VAP?
- IDSA/ATS consensus definition for VAP: new and persistent infiltrate on chest imaging and then evidence that the infiltrate is infectious (leukocytosis, fever, purulent secretions, hypoxia)
- Find the IDSA/ATS Clinical Practice Guidelines on VAP here: Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society [published correction appears in Clin Infect Dis. 2017 May 1;64(9):1298] [published correction appears in Clin Infect Dis. 2017 Oct 15;65(8):1435] [published correction appears in Clin Infect Dis. 2017 Nov 29;65(12):2161]. Clin Infect Dis. 2016;63(5):e61-e111. doi:10.1093/cid/ciw353
- Find the International ERS/ESICM/ESCMID/ALAT guidelines for VAP here
- So let’s break this down further like Owen did in the episode:
- Radiographic criteria:
- Quote from the episode: “You can hallucinate a lower lobe infiltrate in almost any ICU pt”. The point being that especially with portable films, chest x-rays are often not terribly helpful
- There are specific CXR findings though that have high positive likelihood ratios: fissure abutment and air bronchograms should make you strongly favor VAP!
- Also the lack of infiltrate has a sensitivity approaching 90%, but it is rare to see this in critically ill patients
- Owen discussed that there is some data that chest CT can be helpful in refining the diagnosis of radiographically equivocal cases of VAP on CXR:
- Clinical criteria:
- Owen discussed how there are limitations of using fever/leukocytosis in isolation, and even when present, they often barely move the needle
- Fever +2.5%, WBC +3.5%, Purulent secretions +3.5%, Hypoxia 1-2%
- Hypoxia is also limited in helping refine the diagnosis, but it changes the imperative to treat
- Owen mentioned CPIS (Clinical Pulmonary Infection Score), which some people use to try to quantify the likelihood of VAP. Many feel that CPIS should not be relied on as it is not terribly sensitive or specific (and guidelines don’t recommend it it), but you might like to see some of the included factors. Here is the MDCALC link
- Owen’s advice: try to categorize as: 1) confidently not VAP, 2) confidently VAP, 3) don’t feel comfortable ruling in or out
- Then make the decision to treat #3 based on 1) severity of illness of patient and 2) presence/absence of compelling alternative diagnoses.
- Radiographic criteria:
- Check out this resource: Klompas M. Does this patient have ventilator-associated pneumonia?. JAMA. 2007;297(14):1583-1593. doi:10.1001/jama.297.14.1583
- Like in our previous HAI School episodes, remember that there is a difference between the clinical diagnosis/definition and CDC/NHSN criteria. Rates of VAP are of significant interest to ICUs and institutions, so the CDC/NHSN definition are used for hospital performance and infection prevention reporting
- NHSN surveillance definition:
- NHSN = CDC’s National Healthcare Safety Network (NHSN), which is a HAI tracking system
- Here’s the NHSN document with more details on ventilator associated events, updated Jan 2023
- NHSN surveillance definition:
- Additional references:
- Fàbregas N, Ewig S, Torres A, et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax. 1999;54(10):867-873. doi:10.1136/thx.54.10.867
- Fernando SM, Tran A, Cheng W, et al. Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med. 2020;46(6):1170-1179. doi:10.1007/s00134-020-06036-z
So we established the challenges of diagnosing VAP – so what can we consider to prevent overdiagnosis? Here are Owen’s four diagnostic stewardship tricks (life hacks) to help practice VAP antimicrobial stewardship.
VAP does not resolve in <24 hrs
- Clinical decompensations that rapidly improve or normalize in 24h aren’t pneumonia and shouldn’t be treated. Pneumonia is one of the only infections we don’t have source control for, and therefore shouldn’t resolve rapidly.
- These respiratory decompensations might be related to aspiration pneumonitis, mucous plugging, pulmonary edema, or other factors
Don’t “pan-culture” for fever and leukocytosis
- Don’t pan culture for fever/WBC without localizing pulmonary features. Pretest probably is low, and culturing doesn’t move the needle.
- Owen R. Albin, MD, Louis Saravolatz, II, MD, Joshua Petrie, Ph.D. MPH, Oryan Henig, MD, Keith S. Kaye, MD, MPH, Rethinking the ‘Pan-culture’: Clinical Impact of Respiratory Culturing in Patients with Low Pretest Probability of Ventilator-associated Pneumonia, Open Forum Infectious Diseases, 2022;, ofac183, https://doi.org/10.1093/ofid/ofac183
Not all increased secretions are purulent. Talk to the ICU nurses and respiratory therapists about the secretions!
- Causes of nonpurulent/increased secretions include:
- Return of cough + mucociliary clearance
- Pulmonary edema
- Changes in vent circuit humidification
- Diuresis
Respiratory cultures tell you how to treat VAP, not whether to treat VAP
- Respiratory cultures are not binary – use additional information from the culture such as the degree of WBC on gram stain
- A negative Gram stain has an exquisite negative predictive value for VAP that approaches 95%
What is generally the best approach to obtaining a respiratory culture?
- Owen discussed invasive vs non-invasive sampling. The European and International guidelines recommend BAL, but the American guidelines say the opposite and do not preference distal lung sampling (suggesting a proximal lung sample like endotracheal aspirate is sufficient)
- There are some prospective trials comparing invasive vs noninvasive lung sampling, and there was no clear benefit of one way vs the other on clinical outcomes like mortality or vent dependence
- Owen explained that he does prefer a BAL if possible and patient does not have contraindication (such as severe hypoxemia, predisposition to bleeding, new anastomotic site, etc) – particularly since a nonbronchoscoicy BAL (mini-BAL) can be done
Management of VAP
- Empiric vs definitive antibiotic choice
- Inappropriate empiric therapy associated with mortality penalty in multiple studies.
- Choice of agent–you can find differences in literature regarding vanc vs linezolid for MRSA; combo therapy for MDR-GNRs etc, but Owen emphasized that the most important thing is being thoughtful about PK/PD considerations (extended infusion beta-lactams, drug penetration/effectiveness in alveolar space, etc) – befriend a good ID pharmacist!
- Some exceptions: no aminoglycoside or tigecycline monotherapy, no daptomycin
- Treatment duration
- Standard therapy for VAP is generally 7 days.
- There is observational data supporting 3 days of therapy in VAP patients on minimal vent settings, but this is not presently standard of care.
- A little bit on the literature:
- There was a 2003 RCT from France which randomized 8 vs 15 days of antibiotic therapy for VAP in adults:
- Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-2598. doi:10.1001/jama.290.19.2588
- Looked at rates of mortality, vent dependence, organ dysfunction free days – and found no difference
- The big sticking point though was a subgroup analysis of patients with VAP caused by non-fermenting Gram negative bacilli (like Pseudomonas, Acinetobacter, Stenotrophomonas) with increased rates of recurrent pneumonia in those allocated a shorter course
- So for a long time, many experts recommended 2 week course of antibiotics for Pseudomonal VAP
- Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;2015(8):CD007577. Published 2015 Aug 24. doi:10.1002/14651858.CD007577.pub3
- The new IDSA/ATS guidelines then came out and said: it doesn’t matter what the pathogen is, in most cases 7 days of therapy is fine
- There is a relative newer study on Pseudomonas VAP (iDIAPSON) which caused a bit of debate but stated that shorter course therapy was not noninferior to longer course therapy when using composite outcome of death or recurrent pneumonia for Pseudomonal VAP
- Bouglé A, Tuffet S, Federici L, et al. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial [published correction appears in Intensive Care Med. 2022 Jun 21;:]. Intensive Care Med. 2022;48(7):841-849. doi:10.1007/s00134-022-06690-5
- Owen argues that this was massively underpowered to answer the research question
- You can read more about the debate here in some of these comments:
- Citerio G. Shorter might not always be better: the case for longer antibiotic therapy for Pseudomonas aeruginosa pneumonia. Reply of the Editor in Chief. Intensive Care Med. 2022;48(7):965-966. doi:10.1007/s00134-022-06758-2
- Siegrist EA, Sassine J. Shorter might not always be better: the case for longer antibiotic therapy for Pseudomonas aeruginosa pneumonia. Intensive Care Med. 2022;48(7):963-964. doi:10.1007/s00134-022-06754-6
- Albin OR, Kaye KS, McCreary EK, Pogue JM. Less is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-associated Pneumonia [published online ahead of print, 2022 Sep 21]. Clin Infect Dis. 2022;ciac784. doi:10.1093/cid/ciac784
- Metersky ML, Klompas M, Kalil A. Less is More: A 7-day course of antibiotics is the evidence-based treatment for Pseudomonas aeruginosa Ventilator-associated Pneumonia [published online ahead of print, 2022 Oct 5]. Clin Infect Dis. 2022;ciac809. doi:10.1093/cid/ciac809
- There was a 2003 RCT from France which randomized 8 vs 15 days of antibiotic therapy for VAP in adults:
- Owen tries to consider who was excluded from the 2003 RCT: immunocompromised patients, really sick patients, those who had empiric antibiotics that didn’t cover pathogen (so potentially weeded out folks with MDR pathogens) >>> Owen considers long treatment if a combination of factors such as immunocompromised status, critical illness (multipressor dependent circulatory shock, ARDS, ECMO), very delayed clinical response to treatment
- Is there a role for inhaled antibiotics?
- Inhaled antibiotics are attractive because of a really large therapeutic window: would be delivering huge doses into alveolar space with relatively little systemic absorption (although can get some systemic absorption)
- But it’s likely that these inhaled antibiotics in pneumonia patients with significant amounts of pus in the lung, don’t get to the places they need to
- There is retrospective data and a meta-analysis that suggests inhaled antibiotics may be beneficial for folks with MDR or XDR Gram negative pathogens but don’t seem beneficial in most clinical trials
- So Owen does not encourage routine use but says he might consider if there is a severe pneumonia with recurrent infection and few antibiotics options
Infographics
Goal
Listeners will be able to diagnose and treat ventilator-associated pneumonia
Learning Objectives
After listening to this episode, listeners will be able to:
- Describe the epidemiology and risk factors for ventilator associated pneumonia (VAP)
- Summarize the approach to diagnosis of VAP and its challenges
- Discuss treatment of VAP, including duration of therapy
Disclosures
Our guests (Sam Schuiteman and Owen Albin) as well as Febrile podcast and hosts report no relevant financial disclosures
Citation
Albin, O., Schuiteman, S., Dong, S. “#63: HAI School: A Febrile Bundle on Healthcare-Associated Infections #4 – VAP, Crackle, Pop!”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/21609f65-00a8-4a70-9546-8726b7695cbd