Segment Description: Thomas Lodise, PharmD, PhD, professor, Albany College of Pharmacy, reviews the 2019 CAP guidelines and highlights areas that could be improved in future updates.
Interview transcript: (modified slightly for readability)
The question is, how can the guidelines be improved? I’ve served on guidelines committees. It’s challenging, you have to rely on available evidence to make decisions within certain criteria.
I appreciate them maintaining a current stratification. I think this is something we're all familiar with, and thinking about outpatients, whether or not they have comorbidities, and treatment selection, whether they're in the inpatient ward or within the ICU, and providing some guidance on how to handle patients at risk for MRSA and Pseudomonas.
So I think their overall structure and stratification really provides a good framework for identifying what drugs could potentially be considered for your patient and also to provide some clarity even though they may not make a strong recommendation of one recommendation over another, because they usually give a few options some of the guiding evidence and principles which may lead you to take one drug combination over another for example, in patients within the ICU.
I appreciate the move away from HCAP, and, to streamline clinicians to check prior culture data. Given the importance of getting it right the first time, I wish they were a bit more aggressive. They do recommend empirically covering MRSA and Pseudomonas in patients with risk factors for those if they have severe pneumonia, which is basically pneumonia in septic shock. However, my fear is we may undertreat a few patients who could potentially progress to septic shock. I think their recommendation for this was based on the best available evidence showing that we overtreat drug-resistant pathogens. But I still think we have to have a bit more in a bit more work in that area, because there's a recommendation to rely on institute validated risk factor scores. And this is something that a lot of institutions do not have.
So I do think there's an opportunity to better clarify who is our CABP patients at risk for MRSA, pneumonia and Pseudomonas pneumonia, more than just having it on a prior culture or current culture or PCR nares test. The other thing I think they could have done is provided a bit more clarity on the role of new drugs. As I mentioned before we have lefamulin and omadacycline. Omadacycline is mentioned twice in the document lefamulin is mentioned once and both in the future research direction section, citing limited experience.
Why this is true? These 2 agents have gone through recent FDA guidance for approval. There’s a focus on patient-reported outcomes, symptomatic improvement. So these are all things that are of value and they moved away from a lot of test to cure assessment, which was a clinician assessment of the patient's response.
Lefamulin has 2 phase 3 clinical trials and omadacycline has 1. So I think we could add defining their roles in therapy, perhaps not as first-line therapy but for patients at high risk for a fluoroquinolone associated adverse event. If you just look at the packet insert of the fluoroquinolones, there's a lot of class effects listed, you know, aortic aneurysm, patients over 65 [years of age], cardiac conditions, hypertension, patients with renal failure; these are all at increased risk of certain adverse events associated with fluoroquinolones.
So I think there was an opportunity there within the guidelines to better perhaps define the use of our newer drugs in those patients. Alternatively, they can say in those patients, maybe there should be preferential use of a β-lactam with a macrolide. I think these are opportunities, but recognizing that the guideline committee relies on best available agents and with the newer agents, you only have phase 3 clinical data, 2 clinical trials with lefamulin, 1 with omadacycline.
So I appreciate the need for further data, but I think in clinical practices we have these fluoroquinolones which are our go-to CABP drugs, they have tremendous efficacy, you'll never have a more efficacious drug class than fluoroquinolones in patients with CABP; however, from our federal government—and this is also with the EU as well—they identify a number of serious adverse events.
Looking at overall fluoroquinolones use, these adverse events are low, but they do identify some high-risk patient populations. So in the next iteration of the guidelines now it's taken us 12 years to get this one. When will this occur? I do not know. But I think all clinicians would benefit from better clarity on what drugs we should use in patient populations at high risk for fluoroquinolone adverse events, given that they have historically been one of our go-to agents for patients with community-acquired bacterial pneumonia.