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In treating most exacerbations of chronic obstructive pulmonary disease (COPD) the usual regimen consists of prednisone plus 5- to 7-days of antibiotics. But what if a shorter course of antibiotic therapy would do? That would be both convenient for patients and less likely to promote antibiotic resistance.

A recent paper in Therapeutic Advances in Respiratory Disease describes just such a strategy: patients received prednisone plus either 2 or 7 days of levofloxacin. There was no substantive difference in clinical results between the groups. Summarized in NEJM Journal Watch General Medicine as “practice changing,” this research seems worth a closer look.

To that end we’ve invited two of the researchers and the Journal Watch editor who wrote the summary to discuss the issues raised.

Have a listen to this 14-minute Clinical Conversation.

(A note of no great consequence: We’ve called this “Podcast 298” because, while numbering the titles, your host negligently skipped from 297 to 299 in his haste to achieve 300 episodes.)

Therapeutic Advances in Respiratory Disease paper

Journal Watch summary

TRANSCRIPT

Joe Elia:

A recent summary in NEJM Journal Watch Journal 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 Messous, the study’s first author, and Dr. Semir Nouira, 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 Journal Watch General Medicine. Dr. Messous and Dr. Nouira are in the Emergency Department and the Department of Laboratory Research at Monastir University in Tunisia. Welcome to you both.

Dr. Semir Nouira: 

Thank you very much. Welcome.

Dr. Salma Messous:

Thank you very much.

Dr. Daniel Dressler: 

Thank you so much, Joe. Welcome, again, to Dr. Messous and Dr. Nouira.

I’ll just jump in and ask you if you would agree with 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.

Dr. Semir Nouira:

Thank you, Dan, for your choice of our study. I’m very proud to be here and to be with you to explain the background of our study and the results of our study.

Our study is probably the first that compares a short course of antibiotic — as short as two days — compared to seven days’ conventional duration. We found that there are similar results, and that the two-day is as effective as seven days.

You know, 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 shown many years ago — I can say at least since 2008, since the publication of the first analyses comparing the efficacy between short and a conventional course. So years ago it was shown, this evidence.

This was not our question, and as you can expect, this is very important as a result to know, it’s very important, it’s very relevant because this would 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. This is the main question of the study, and you know that according to a recent recommendation of the GOLD, it is recommended that antibiotic therapy should not exceed five days, and some studies demonstrate that even with three days, we can have similar results as conventional duration. So for us, the question is, could we decrease the duration to less than three days? And that’s why we performed this study because according to in vitro and animal studies, antibiotic therapy has its maximum effect during the first hours, so why not reduce antibiotic therapy to the least duration?

This was the background of our study, and fortunately, we demonstrate that we had similar clinical outcome with respect to clinical cure, to the need for additional antibiotic therapy, to the need for ICU admission, and to the duration of the exacerbation-free interval. So this is the background of our study, and these are the main findings of our study.

Joe Elia: 

I wanted to ask you, Dr. Dressler, why you consider the research practice-changing or potentially so. Is the 5- to 7-day regimen baked into the current guidelines here?

Dr. Daniel Dressler:

Sure, and thank you, Dr. Nouira for that answer and response.

I also appreciate that there have been maybe some other studies that have suggested shortening the course for COPD is probably appropriate, and yeah, still the GOLD guidelines or the international guidelines for management of COPD and COPD exacerbation still are recommending even in 2022 this 5- to 7- 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 than the 5 days, even shorter than a 3 day course. I think that you were able to demonstrate that in your patient population the equivalence in outcomes even with a 2- day course compared to a 7-day course, and so I find that really valuable, really impressive. And you say it can also really help clinicians feel comfortable that they can actually shorten the course. Maybe it will impact or influence guidelines in the future to help maybe suggest a shorter course. 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.

Joe Elia: 

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. Messous, your design was practical in nature. 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?

Dr. Salma Messous:

So, it’s a bit early to make recommendations. We need larger studies. This may allow us to better target our recommendations for the duration of antibiotic therapy, for example, according to their age, the existence of pulmonary edema, comorbidity, biomarkers, et cetera. So maybe Professor Nouira can add a comment regarding this question.

Dr. Semir Nouira:

Thank you, Salma, for your answer. What I can add as to whether there is enough data to recommend two-day regimen 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 in my opinion, there are two recommendations and two directions for future investigation.

First, we must have more investigation to select patients who need antibiotics for COPD exacerbation. This is the first step, and it’s a big challenge now. It’s very widespread to give antibiotics, and unfortunately, until now, we don’t know the best profile of patients 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 is the optimal duration of the antibiotic course. I think it can be two days. It can be more. It can be less. It probably depends, as said by Salma, on the patients. Probably we will recommend antibiotic duration according to the patient’s characteristics, biomarkers or clinical characteristics such as age, sex, or comorbidities or something like that. So I think it’s really early to recommend a two-day antibiotic therapy for acute exacerbation of COPD.

Dr. Daniel Dressler:

Thank you for those answers to Joe’s questions.

I will say also that I’m glad you brought up patient population and determining which patients need antibiotics at all for COPD exacerbation. I think you all did a nice job in trying to identify those patients and not including patients that did not meet the sort Anthonisen 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 that. I think your study did a very nice job even with only about 300 patients and it’s 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 has been the reaction of your colleagues related to this research and these outcomes that you found?

Dr. Semir Nouira:

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 examples are numerous. You know, despite the evidence that a short course of antibiotics is as effective as conventional course, I think more than half of the physicians continue to prescribe antibiotic for at least seven days, and this is evident, so it’s a 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 effort. We must not limit ourselves to recommendation, but we must follow this recommendation and try to translate these recommendations into clinical practice, and this is our job.

Dr. Daniel Dressler:

Greatly appreciated, as well, and hopefully, we’re helping do something with you.

Joe Elia:

I want to thank you, Dr. Messous and Dr. Nouira, and Dr. Dressler for this chat today.

Dr. Semir Nouira:

Thank you, Joe.

Dr. Salma Messous:

Thank you, Joe, very much.

Dr. Semir Nouira:

Thank you very much, Dan.

Joe Elia: 

We will call that the 298th edition of clinical conversations all of which are available free at podcasts.jwatch.org. We come to you from the writers and editors of the NEJM Group. Our executive producer is Kristin Kelley, and I’m Joe Elia. Thanks for listening.