In this episode, I’ll discuss a gram stain-based algorithm for antibiotic selection in patients with suspected VAP.
The way the IDSA 2016 VAP guidelines are written, every patient with suspected VAP ends up receiving MRSA coverage plus one to two antipseudomonal agents. These are presented as strong recommendations based on low-quality evidence.
The guideline authors also state:
These recommendations are a compromise between the competing goals of providing early appropriate antibiotic coverage and avoiding superfluous treatment that may lead to adverse drug effects, Clostridium difficile infections, antibiotic resistance, and increased cost.
A group of researchers from Japan has been working on using the gram stain from tracheal aspirates in patients with suspected VAP to more narrowly guide the selection of empiric antibiotics.
Their proposed algorithm in patients with suspected VAP is as follows:
- In patients with septic shock, an antipseudomonal carbapenem and anti-MRSA agent are combined
- If septic shock is not present, an assessment of multi-drug resistant risk is made
- High-risk patients are defined as those with at least one of the following: antimicrobial therapy in the preceding 90 days, a hospital stay of 96 hours or more, chronic dialysis, immunosuppressive disease or therapy, nursing home admission, or colonizing MDR pathogens from surveillance cultures of endotracheal aspirate collected once a week
- Low-risk patients are those without the above risk factors
- Low-risk patients receive a non-pseudomonal beta-lactam
- High-risk patients undergo tracheal aspiration and gram staining and receive antibiotics according to the gram stain
- Gram-positive bacilli = treat as low risk with a non-pseudomonal beta-lactam
- Gram-positive cocci in chains = treat as low risk with a non-pseudomonal beta-lactam
- Gram-positive cocci in clusters = treat with an anti-MRSA agent
- Gram-negative rods = treat with an anti-pseudomonal beta-lactam
- Patients without septic shock only receive anti-MRSA and anti-pseudomonal therapy if the gram stain shows both gram-negative rods and gram-positive cocci in clusters
This algorithm was first applied to a retrospective cohort of 131 patients and hypothetically compared with guideline-recommended empiric treatment. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (guideline based = 95.4% versus gram stain based = 92.4%; p = 0.134).
The number of episodes for which anti-MRSA agents were selected as an initial treatment was 71.0% in the guideline-based group versus 31.3% in the gram stain based group. The number of episodes for which anti-pseudomonal agents were recommended as initial treatment was 70.2% in the guideline-based group versus 51.9% in the gram stain based group. Both of these differences were statistically significant.
Recently, the same authors applied this algorithm to 19 patients in a prospective observational study. The algorithm provided appropriate antimicrobial coverage in all but one patient (94.7% appropriate). The algorithm provided narrower-spectrum antibiotics in 78.9% of patients compared to if the VAP guidelines had been applied. The primary outcome of the clinical response rate of VAP was 68.4%, which the authors state is comparable to previous trials in similar clinical settings.
On the basis of the promising results of this algorithm, the authors are conducting a multicenter, randomized, non-inferiority trial (GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP)) to compare gram stain-guided treatment with guidelines-based treatment for patients with VAP. The estimated primary completion date for this study is March 31, 2021.
Until the randomized trial is published, the evidence supporting this algorithm is weak. However, so is the evidence that underlies the current guideline recommendations for empiric VAP treatment. In fact, the only evidence cited to support this strong guideline recommendation are surveillance studies and observational trials that suggest inadequate antibiotic therapy for VAP is associated with a higher risk of death.
Institutions looking to aggressively narrow empiric antibiotics for patients with VAP may explore the use of this algorithm, but most will likely wait for changes to the IDSA guideline or stronger evidence in the form of a randomized trial.
To get a free pdf of my visual critical care antibiotic guide to help you easily remember spectrum of activity, go to pharmacyjoe.com/abx.
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