Podcast 298: COPD exacerbations — 7 days of antibiotics versus 2

Summary

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Clinical Conversations – Episode 298:

COPD Exacerbations — 7 Days of Antibiotics versus 2

Date: August 2, 2022
Host: Joey Alia (A)
Guests:

• Dr. Daniel Dressler (C), Professor of Medicine, Emory University; Deputy Editor, NEJM Journal Watch General Medicine
• Dr. Salma Mesus (B), First Author of the Study; Monastir University, Tunisia
• Dr. Samir Nuira (B), Senior Author; Monastir University, Tunisia

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Main Theme

This episode explores a potentially practice-changing study comparing two versus seven days of antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD). The hosts and study authors discuss the rationale, findings, clinical implications, and real-world adoption challenges of shortening antibiotic courses in COPD, focusing on efficacy, guideline impact, and antibiotic stewardship.

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Key Discussion Points & Insights

1. Background and Study Rationale

[00:00–05:22]

• Current Standard of Care: Guidelines (GOLD/international) recommend five to seven days of antibiotics for COPD exacerbations.
• Known Evidence: Prior research and multiple meta-analyses have shown short-course (three to five days) antibiotics are as effective as conventional length for certain infections, but the absolute shortest effective duration remained unclear.
• Study Objective: Determining whether an even shorter course of antibiotics — just two days — could be as effective as seven days, potentially reducing resistance, adverse effects, and improving compliance.

Notable Quote

“Our trial is probably the first that compare a short course of antibiotic as short as two days compared to seven days... And we found that there are similar results and two days is as effective as seven days.” — Dr. Salma Mesus [01:43]

Rationale for Study

• Guidelines and Evidence Gap: Despite evidence supporting shorter durations, actual recommendations still suggest longer courses.
• Antibiotic Stewardship: Reducing unnecessary antibiotic exposure could have far-reaching benefits in resistance and safety.

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2. Study Design and Main Findings

[00:57–05:22]

• Randomized, ~300 Patients: Acute COPD exacerbations assigned to either two or seven days of levofloxacin.
• Co-Interventions: All participants also received corticosteroids.
• Outcomes Measured: Clinical cure, need for additional antibiotics, ICU admission, and exacerbation-free interval.
• Findings: Two-day course resulted in similar clinical outcomes as the seven-day regimen.

Notable Quote

"What is the shortest course of antibiotics that we can accept for our patient COPD patients with exacerbation? And this is the main question of the study... we demonstrate that we had similar clinical outcome." — Dr. Salma Mesus [04:05]

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3. Practice-Changing Potential

[05:22–07:08]

• Host & Expert Perspective:
  • Dr. Dressler and host emphasize how the study challenges entrenched guidelines and could make clinicians more comfortable prescribing shorter (even two-day) regimens.
  • Potential for wider adoption if further validated.

Notable Quote

"I applaud you for what you’ve done... And so I think that is why I consider it a value added piece of medical literature... and something that we can practice on and maybe practice changing for many clinicians." — Dr. Daniel Dressler [06:36]

• Guideline Lag: Despite mounting evidence, practice often fails to keep up with research findings or changes slowly.

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4. Adoption, Limitations, and Real-World Impact

[07:08–13:31]

• Clinical Practice & Generalizability
  • Still too early to universally recommend the two-day regimen—needs larger studies, more data across diverse patient groups, and careful patient selection.
  • Duration may need tailoring to patient demographics, presence of comorbidities, and biomarkers.
  • Currently, their institutions and others have not adopted two-day regimens as standard.

Notable Quotes

"So it's a bit early to make such recommendations. We need larger studies... according to the age, the existence of comorbidity, biomarkers, etc." – Dr. Salma Mesus [08:12]

"With the available evidence we can't recommend two days. But... we must have more investigation to select patients who need antibiotic for COPD exacerbation. This is the first step and it's a big challenge." — Dr. Samir Nuira [09:16]

• Changing Physician Behavior
  • Difficulty in translating research to practice; most physicians continue to prescribe longer courses.
  • Emphasis on ongoing efforts to improve visibility and implementation of new evidence in clinical routines.

Notable Quote

"It's a very big challenge to translate scientific results into clinical practice... despite the evidence... more than half of physicians continue to prescribe antibiotic for at least seven days." — Dr. Salma Mesus [12:17]

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5. Study Strengths and Community Reception

[10:54–13:31]

• Study Sample: About 300 patients, similar to many other major COPD studies.
• Colleague Reaction: Enthusiastic but cautious; awareness of resistance to rapid practice change.
• International Alignment: The challenge is not unique to Tunisia; similar inertia worldwide.

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Notable Quotes & Memorable Moments

| Timestamp | Speaker | Quote | |-----------|---------|--------------------------------------------------------------------------------------------------------| | 01:43 | Dr. Mesus | “...two days is as effective as seven days.” | | 05:38 | Dr. Dressler | “...you were able to demonstrate that in your patient population that equivalence in outcomes even with a two day course compared to a seven day course.” | | 08:12 | Dr. Mesus | “So it's a bit early to make such recommendations. We need larger studies...” | | 12:17 | Dr. Mesus | “It’s a very big challenge to translate scientific results to clinical practice...” |

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Important Segment Timestamps

• [00:00–01:43] — Introduction & study background.
• [01:43–05:22] — Study rationale, design, and main results.
• [05:22–07:08] — Significance and potential to change clinical guidelines.
• [07:08–10:54] — Feasibility of wide adoption, recommendations, and future research priorities.
• [10:54–13:31] — Difficulties in changing clinical culture and international perspectives.
• [13:31–13:49] — Wrap-up and thanks (end of content).

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Overall Tone

The conversation is collegial, evidence-focused, and gently optimistic, with all participants stressing scientific rigor, the importance of broader validation, and the need for clinical prudence before shortening antibiotic courses for all. The authors and reviewers alike acknowledge the real-world barriers to adopting new evidence and advocate for continued research and dissemination to ultimately improve patient care and antibiotic stewardship.

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Transcript

[A]

A recent summary in NEJM JournalWatch General Medicine labeled a study about treating acute exacerbations of chronic obstructive pulmonary disease, or copd, as practice changing. So it seems important to spread the news. To do that, we've got Dr. Daniel Dressler, the summarizer of the study, Dr. Salma Mesus, the study's first author, and Dr. Samir Nuira, a senior author, to discuss it with us. Dr. Dressler is a professor of medicine at Emory University in Atlanta. He is also deputy editor of NEJM General Watch General Medicine. Dr. Mesus and Dr. Noira are in the Emergency Department and the Department of Laboratory Research and at Monastir University in Tunisia. Welcome to you both.

[B]

Thank you very much. Welcome.

[C]

Thank you so much, Joe. And welcome again to doctors Masseuse and Noira. I'll just jump in and go ahead and ask you if you would agree with sort of this thumbnail description of your work. You randomized approximately 300 patients with acute exacerbation of COPD to one of two antibiotic regimens, either a two day course of levofloxacin or a seven day course, which is the usual care. So I'll ask you if that's correct and if you can tell us briefly why you undertook this study and essentially what you found.

[B]

Thank you, Dan, for your choice of our studies. I am very proud to be here and to be with you to explain the background of our study and the results of our study. Our trial is probably the first that compare a short course of antibiotic as short as two days compared to seven days. It's conventional duration. And we found that there are similar results and today is as effective as seven days. You know that actually the objective of the study is not to show or to demonstrate the similarity between short course and conventional course of antibiotics. This was clearly showed many years ago. I can say at least since 208 since the publication of the first meta analysis about the efficacy and the comparison between the efficacy of the efficacy between short and conventional course. So many years ago it was shown this evidence. This was not our question. And as you can expect, this is very important as a result. You know, it's very important. It's very relevant because this will lead to less consumption of antibiotics, less antibacterial resistance, less adverse effects and perhaps more compliance. So this was demonstrated many years ago. But the question of the present study is the following. What is the shortest course of antibiotics that we can accept for our patient COPD patients with exacerbation? And this is the main question of the study. And you know that the according the recent recommendation of the gold, it is recommended that antibiotic therapy should not exceed five days. And some studies demonstrated that even with three days we can have similar results as conventional duration. So for us the question is could we decrease this duration to less than three days? And that's why we performed this study because according to in vitro and animal studies antibiotic efficacy it had its maximum of effect during the first hours. So why not reduce antibiotic therapy to the least duration? This was the background of our study. Fortunately we demonstrate that we had similar clinical outcome with respect to clinical cure, to the need for additional antibiotic therapy, to the need to ICU admission and to the duration of exacerbation free interval. So this is the background of our study and this is the main finding of our study.

[A]

I wanted to ask you Dr. Dressler, why you considered the research practice changing or potentially so is the five to seven day regimen baked into the current guidelines here?

[C]

Sure. And thank you Dr. Moira for that answer and response. And I appreciate also that there have been maybe some other studies that have suggested shortening the course for COPD is probably appropriate. And yet there's still the gold guidelines or the international guidelines for management of COPD. And COPD exacerbations still is recommending even in 2022 this five to seven day course of antibiotics. And so I applaud you for what you've done, which is trying to see well, can we get even shorter, shorter than the five days, even shorter than a three day course. And I think that you were able to demonstrate that in your patient population that equivalence and outcomes even with a two day course compared to a seven day course. And so I find that really valuable, really impressive as you say. It can also really help clinicians feel comfortable that they can actually shorten the course and maybe it will impact or influence guidelines in the future to help maybe suggest a shorter course. And so I think that is why I consider it a value added piece of medical literature and clinical literature and something that we can practice on and maybe practice changing for many clinicians.

[A]

You also noted in your comment, Dr. Dressler, that the findings need to be confirmed and more work needs to be done in this area. But I can see the advantage of having a patient only taking two days and not trying to take a seven day course. Dr. Metsos, your design was practical in nature, wasn't it? By that I mean some patients remained in the hospital even while on the two day course. If it was considered clinically PRUDENT to do so. And of course everyone received prednisone intravenously or by mouth if they were at home. Do you think you've got enough data to recommend two day regimen as routine and do your hospitals use the two day regimen now?

[B]

So it's a bit early to make such recommendations. We need larger studies. This may allow us to better target the recommendations concerning the duration of antibiotic therapy, for example, according to the Age, the existence of comorbidity, biomarkers, etc. So maybe Professor Nvira can add comment regarding this question. Thank you Selma for your answer. What I can add for this question, whether there is enough data to recommend 2 days regiment as routine treatment. The answer of course is no, because I think there's not enough data for that. With the available evidence we can't recommend two days. But there is, in my opinion there is two recommendations and two direction for future investigation. First, we must have more investigation to select patients who need antibiotic for COPD exacerbation. This is the first step and it's a big challenge. You know, it's a very sprayed to give antibiotics and unfortunately until now we don't know what is the best profile of patient who really need antibiotics. So this is the first step, the second step and the second direction, once the first step is clearly answered, is to try to know what, what is the optimal duration of antibiotic course? I think it can be two days, it can be more, can be less. It probably depends as said by Selma, on the patients, probably we will recommend antibiotic duration according to the patient characteristics, demographic characteristics of or clinical characteristics or other some such as biomarkers, such as age, sex or something like that. So I think it's really early to answer or to recommend today antibiotic therapy for acute exacerbation of copd.

[C]

Well, thank you for those answers to Joe's questions. And I will say also that I'm glad you brought up patient population and are we determining which patients need antibiotics at all for the MC or PD exacerbation? And I think you all did a nice job in trying to identify those patients and not including patients who did not meet the sort of anthemicin criteria for requiring antibiotic therapy or potentially needing antibiotic therapy. So I appreciate that. And because we have other data that suggests that potentially patients with COPD exacerbation that are low risk, you know, whether or not they need antibiotics at all, you may be getting to some of it, some of that. So I think your study did a very nice job in Even with only about 300 patients, it is still comparable to many studies in COPD in terms of size. And so I appreciate the work that you all have done. I'm wondering what was in the reaction of your colleagues related to this research and these outcomes that you found?

[B]

You know, this is a very big challenge. You know, it's a very big challenge to translate scientific results into clinical practice. It's not easy at all, even in the developed countries. And the example are very numerous. You know, despite the evidence that short course of antibiotics is as effective as conventional courts, I think more than a half of the physician continue to prescribe antibiotic for at least seven days. And this is evident. So it's very big change. And for the Tunisian physician, it's the same issue. Of course, there's no reason to be different. You know, perhaps we need to do more to make our results more visible. So it's the future of our efforts. We must not limit ourselves to recommendation, but we must follow this recommendation. Try to make the tradition of this recommendation in clinical practice. And this is our job.

[C]

Greatly appreciate that as well. And hopefully we're helping do something with you.

[A]

I want to thank you, Dr. Mesuz, Dr. Noira and Dr. Dressler for this chat today.

[B]

Thank you, Joe. Thank you very much, Dan.

[A]

We will call that the 298th edition of Clinical Conversations, all of which are available [e-mail] we come to you from the writers and editors of the NEJM Group. Our executive producer is Kristen Kelly and I'm Joey Alia. Thanks for listening.