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Shortening the Course: What’s New with Duration of Therapy? · The SHEA Podcast

• 0:08
  SPEAKER_00: Welcome to our podcast series, Antimicrobial Stewardship Popoe, brought to you by the Society for Healthcare Epidemiology of America, Shay, promoting the prevention of healthcare associated infections and antibiotic resistance and seeking to advance the field of healthcare epidemiology and antibiotic stewardship.
• 0:27
  SPEAKER_00: This series will discuss communication techniques for antimicrobial stewardship, evaluate the opportunities and limitations of antimicrobial IV to PO conversion, and identify best practices when shortening durations of therapy.
• 0:41
  SPEAKER_00: If you haven't listened yet to the other two episodes in this series, you should definitely take some time for a listen as they take a seemingly simple topic of IV to PO and highlight some of the different perspectives in both the inpatient and ambulatory settings.
• 0:55
  SPEAKER_00: I'm Dr.
• 0:55
  SPEAKER_00: Rebecca Wren of Duke University Hospital, where I serve as a coordinator of infectious diseases pharmacy programs, the co-chair of the antimicrobial stewardship and evaluation team, director of the PGY2 infectious disease residency programs, and an adjunct associate professor of the Duke School of Medicine.
• 1:12
  SPEAKER_00: And I will be your podcast moderator today.
• 1:15
  SPEAKER_00: She is excited to launch the final episode of the series, which is entitled Shortening the Course, What's New with Durations of Therapy?
• 1:23
  SPEAKER_00: Duration of Therapy is an important target of our antimicrobial stewardship interventions.
• 1:28
  SPEAKER_00: It can be challenging to implement successfully.
• 1:31
  SPEAKER_00: This podcast will briefly review the updated literature, which seems to be coming more frequently recently, and describe best practices when implementing shorter durations of therapy safely within the context of an antimicrobial stewardship program.
• 1:45
  SPEAKER_00: I'm happy to introduce our two speakers for today.
• 1:49
  SPEAKER_00: First, we have Dr.
• 1:50
  SPEAKER_00: Dmitry Draconiev and Chief of the Infectious Diseases Section of the Minneapolis VA Healthcare System, core investigator for the Center for Care Delivery and Outcomes Research, and Associate Professor in the Department of Medicine at the University of Minnesota.
• 2:05
  SPEAKER_00: His clinical research interests include cholesterol defecital infections, urinary tract infections, especially in men, and improving antimicrobial use.
• 2:15
  SPEAKER_00: We're also pleased to have Dr.
• 2:16
  SPEAKER_00: Marissa Holabar, Clinical Associate Professor of Medicine at Stanford University and the medical director of the Stanford Antimicrobial Safety and Sustainability Program.
• 2:26
  SPEAKER_00: Her interests include Staph aureus bacteria, medical education, and global antimicrobial stewardship.
• 2:33
  SPEAKER_00: Thank you both for joining us today.
• 2:36
  SPEAKER_01: Pleasure joining you both.
• 2:37
  SPEAKER_01: Really looking forward to it.
• 2:39
  SPEAKER_02: Thanks for inviting me.
• 2:40
  SPEAKER_02: It's one of my favorite topics.
• 2:42
  SPEAKER_00: Awesome.
• 2:43
  SPEAKER_00: So first we'll begin with community acquired pneumonia.
• 2:47
  SPEAKER_00: Dr.
• 2:47
  SPEAKER_00: Holabar, what does the most recent literature say about the most appropriate duration of therapy?
• 2:52
  SPEAKER_00: Kind of how has this changed over time and how are you implementing it in your institution?
• 2:58
  SPEAKER_02: Thanks, Rebecca.
• 2:59
  SPEAKER_02: So this is a great topic to start with because the evidence base is growing and becoming stronger when it comes to the most appropriate duration of therapy for patients with community acquired pneumonia.
• 3:11
  SPEAKER_02: So to step back, we all know that the US national guidelines have recommended five days of therapy for patients with CAP who meet clinical stability criteria for a long time, for a number of years.
• 3:24
  SPEAKER_02: This is most recently supported by multi-center randomized control trial that was conducted in Spain and published in 2016 that demonstrated that patients who met the IDSA guidelines criteria for clinical stability, which was essentially resolution of vital sign abnormality and ability to take PO antibiotics and normal mentation who were treated with five days of antibiotics had similar outcomes as those treated per clinician discretion.
• 3:54
  SPEAKER_02: And in that study, the median number of days of therapy patients treated per clinician discretion was 10 days.
• 4:01
  SPEAKER_02: So that study established five days was just as good as patients who received 10 days of therapy if they met clinical stability criteria.
• 4:10
  SPEAKER_02: The more recent interesting evidence suggests that some patients can be treated for even shorter durations of therapy.
• 4:17
  SPEAKER_02: There was a multi-center randomized controlled trial that was conducted in France and published in 2021 that randomized 310 adult patients with moderately severe community-acquired pneumonia who'd received 72 hours of beta-lactam monotherapy.
• 4:34
  SPEAKER_02: And they were randomized to receive either five more days of antibiotics or to complete a course of therapy with placebo.
• 4:41
  SPEAKER_02: In order to even be included in this study, patients needed to meet clinical stability criteria.
• 4:47
  SPEAKER_02: And their primary outcome of interest was cure at 15 days after initiation of antibiotics.
• 4:53
  SPEAKER_02: And bottom line, the authors found that three days of beta-lactam monotherapy was non-inferior to eight days of therapy.
• 5:01
  SPEAKER_02: It's important to note that many patients were excluded from this study, most notably patients admitted to the ICU.
• 5:09
  SPEAKER_02: They did not include patients who had respiratory failure or septic shock secondary to CAP.
• 5:14
  SPEAKER_02: They excluded immunocompromised patients and those with renal failure.
• 5:18
  SPEAKER_02: And they also excluded patients who met the now retired definition for healthcare-associated pneumonia, one that's been is no longer included in US national guidelines that were published in 2019.
• 5:31
  SPEAKER_02: But they did include patients of advanced age.
• 5:33
  SPEAKER_02: And the median age of patients included in the placebo arm was 72 and a half years and 74 years in the beta-lactimia arm.
• 5:42
  SPEAKER_02: And over 20% of the patients included had at least one comorbidity.
• 5:47
  SPEAKER_02: This suggests that some adult patients, those who are pretty healthy, who reach clinical stability at three days, probably don't need any more antibiotics.
• 5:57
  SPEAKER_02: There was a study in 2016 that was published in the British Medical Journal and conducted in the Netherlands that randomized about 180 adult patients with mild to moderate severe CAP to three or eight days of antibiotics and found similar success rates between the two groups.
• 6:14
  SPEAKER_02: So there is another study that supports those conclusions.
• 6:18
  SPEAKER_02: So I think this is really interesting and exciting for stewards and for practicing clinicians because it really supports that shorter course of therapy in the right patient population is appropriate.
• 6:30
  SPEAKER_02: I'll just point out there has been some controversy or at least some discussion after this paper was published, because as the authors pointed out in their study limitations, that they may have included some patients who actually didn't have bacterial community acquired pneumonia.
• 6:46
  SPEAKER_02: And some of these patients may have had a viral lower respiratory tract infection, both circumstances for which antibiotics wouldn't be expected to influence their clinical course.
• 6:57
  SPEAKER_02: But practically speaking, on the wards, we don't establish the causative agent in CAT for many of our adult patients.
• 7:05
  SPEAKER_02: So this study is really helpful in that way.
• 7:07
  SPEAKER_02: I think it really depends on a patient reaching clinical stability.
• 7:13
  SPEAKER_02: And then the decision about duration of therapy can be made.
• 7:16
  SPEAKER_02: So it's exciting.
• 7:17
  SPEAKER_00: I completely agree with you.
• 7:19
  SPEAKER_00: I think that practical application is so important there.
• 7:22
  SPEAKER_00: Have there been things that you've done at your institution to implement these changes for the appropriate patients?
• 7:28
  SPEAKER_02: We, like all other programs, include recommendations about duration of therapy and all of our outreach, educational outreach, prospective audit feedback, and our handshake stewardship work.
• 7:40
  SPEAKER_02: But we're hoping to focus on in the near future is optimizing antibiotic prescriptions upon discharge from the hospital.
• 7:47
  SPEAKER_02: I think this audience is aware of the 2019 study, retrospective cohort study of adult patients with community acquired pneumonia that was conducted in over 40 hospitals in Michigan and really drew attention to the opportunity here.
• 8:02
  SPEAKER_02: This group found that two-thirds of the over 6,000 patients enrolled received excess antibiotic therapy, most of which occurred at the time of discharge.
• 8:13
  SPEAKER_02: So, prompted by that study, we looked at some of our internal data and documented that although the mean duration of therapy for patients with CAP admitted to the medicine wards had decreased over time, there were still many patients receiving greater than five days of therapy who were, despite being clinically stable, so meeting criteria for shorter course therapy.
• 8:33
  SPEAKER_02: So I think like this I know our program is not alone by being excited to partner with frontline pharmacists and transition of care pharmacists to kind of ensure patients are getting the most appropriate durations of therapy upon discharge.
• 8:47
  SPEAKER_02: And it's also a great way for stewardship programs to decentralize their efforts and kind of enlist the help of everybody in this work.
• 8:56
  SPEAKER_00: Absolutely.
• 8:57
  SPEAKER_00: Thank you so much for that.
• 8:58
  SPEAKER_00: Both a historic view of kind of how we've gotten down to three days over time and also kind of what you guys are doing at your institution.
• 9:06
  SPEAKER_00: Dr.
• 9:07
  SPEAKER_00: Draconia, do you have anything to add to the community acquired pneumonia and the newer literature?
• 9:12
  SPEAKER_01: No, I'll just, I mean, I'll briefly just note the fabulous review.
• 9:16
  SPEAKER_01: I learned a lot of it, which is like, oh yeah, I remember that.
• 9:19
  SPEAKER_01: We've had similar experiences here.
• 9:21
  SPEAKER_01: And I think for the most part, our clinicians are pretty embracing these new changes.
• 9:26
  SPEAKER_01: I will say that every once in a while you do have a patient who is not reaching clinical stability and reminding clinicians that you know, this is someone where if you haven't met those criteria, then it is okay to keep going.
• 9:37
  SPEAKER_01: And I think that takes a little bit of reassurance, but otherwise it's been going quite well, in my opinion.
• 9:42
  SPEAKER_00: That's great.
• 9:43
  SPEAKER_00: Any day saved is a good day when it's a safe situation, of course.
• 9:48
  SPEAKER_00: All right, let's move on to urinary tract infections.
• 9:51
  SPEAKER_00: So the newest literature, we're getting more literature about the duration of males.
• 9:56
  SPEAKER_00: And Dr.
• 9:57
  SPEAKER_00: Draconi, I know this is an area of interest for you.
• 10:00
  SPEAKER_00: And so, what is new in the literature in this area?
• 10:04
  SPEAKER_01: Yeah, well, so thank you.
• 10:05
  SPEAKER_01: And you know, self-serving answer.
• 10:07
  SPEAKER_01: I mean, we're really pleased to publish a paper we had in this field looking at duration of men without a fever with urinary tract infection.
• 10:16
  SPEAKER_01: This was a relatively pragmatic trial, which we published last year in JAMA.
• 10:20
  SPEAKER_01: It had about 270 some men who were clinically diagnosed with UTI without fever.
• 10:27
  SPEAKER_01: There's previous data from a European study, some Dutch colleagues who included men with febrile UTI, which I'll touch on later.
• 10:34
  SPEAKER_01: But these were men without a fever, and they were treated with either ciprofloxicin or TMP sulfa, which at the time when we started designing the trial were the two most commonly used drugs.
• 10:44
  SPEAKER_01: Frankly, that changed during the trial, and it would have been nice if we could have included others, but we randomized them after a week of therapy to either another week of the same drug, just with a different formulation, or a week of placebo.
• 10:57
  SPEAKER_01: So in week two, all participants were told you're going to be getting a different appearing drug than in week one, and the clinical outcome of clinical cure defined by did you no longer seek care for any recurrence of symptoms?
• 11:11
  SPEAKER_01: And showed that really there was no difference between the seven-day versus the 14-day duration.
• 11:16
  SPEAKER_01: Seven days was non-inferior.
• 11:18
  SPEAKER_01: We looked for adverse events such as C.
• 11:21
  SPEAKER_01: difficile infection, various other adverse events.
• 11:24
  SPEAKER_01: Numerically, they were less, but frankly, there was no statistical difference given that adverse events are, you know, only occurring in a subset, and you just aren't going to have statistical power to find differences there.
• 11:36
  SPEAKER_01: But when you compare this with the, or when you add this to the sort of growing evidence that is out there about duration that the Dr.
• 11:43
  SPEAKER_01: Holobar reviewed, and then all the other data that is out there, which frankly I think Dr.
• 11:47
  SPEAKER_01: Spelberg keeps a wonderful website, sort of tabulating the ever-growing field of shorter versus longer studies.
• 11:55
  SPEAKER_01: I think it really makes it pretty clear that there are very few times where you do need to be treating longer.
• 12:00
  SPEAKER_01: And I just mentioned briefly the prior study from URIC, I believe it's Dr.
• 12:05
  SPEAKER_01: Von Neukoup in BMC infectious diseases from a few years ago, looked at men and women with febrile urinary tract infections and compared seven days of ciprofloxicin versus 14 days of ciprofloxicin.
• 12:19
  SPEAKER_01: And whereas the women did better, the clinical success rate was actually slightly higher in the longer duration.
• 12:26
  SPEAKER_01: So that's really the one area where if you have a man with a urinary tract infection with a fever, I'm not sure we can be certain as saying that seven days is clearly not inferior.
• 12:36
  SPEAKER_01: I think there's at least a circumstance where you might want to consider it where I think some clinical judgment comes into play.
• 12:41
  SPEAKER_01: If your patient is improving and doing well, I would feel fairly comfortable sticking with seven, but if they're slow to recover, I might extend therapy a bit there.
• 12:49
  SPEAKER_01: But that's in a pretty limited subset of those with men with fever.
• 12:53
  SPEAKER_00: Thank you so much for that.
• 12:55
  SPEAKER_00: And I'm glad you touched on the choice of antibiotics that were included, being Bactrum and the fluoroquinolines.
• 13:02
  SPEAKER_00: Do you think there would be any difference if it were beta-lacteans?
• 13:06
  SPEAKER_01: That's an interesting question.
• 13:07
  SPEAKER_01: And historically, the oral beta-lactams have always been a little bit, you know, have been seeing cure rates and success rates a little bit below that of drugs that we feel more comfortable in the urinary tract, such as TMP sulfa or fluoroquinolones.
• 13:22
  SPEAKER_01: But again, now we have much more appreciation of the adverse events of fluoroquinolones.
• 13:27
  SPEAKER_01: So I think we all hesitate to go that route.
• 13:30
  SPEAKER_01: But I think other studies, such as Mack Hooten's study in GEAMA, that looked that compared cefpadoxine with ciprofloxicin, numerically cefpadoxine was slightly less effective in clinical cure.
• 13:41
  SPEAKER_01: This was in women, not men, but it still was a reasonable option.
• 13:46
  SPEAKER_01: So I think it is reasonable to consider you know something like oral beta-lactons, whether it's cephpadoxine or amoxicill glavulinate, but we just don't have that much data there.
• 13:57
  SPEAKER_01: And that's always one of the challenges when you do trials of duration.
• 14:01
  SPEAKER_01: Do you include all drugs, only certain drugs?
• 14:04
  SPEAKER_01: You have more confidence when you limit yourself to only one or two drugs where you can say that, all right, we studied this, but you obviously then can't apply that as confidently to the wide range of antimicrobials used.
• 14:16
  SPEAKER_01: So it's a real challenge for a trialist to make that choice of do you want to focus on a specific drug, which makes it harder to enroll, but you can have more faith in your results, or do you take all comers, but then you worry that are you inappropriately combining drugs that might have individual differences that you just aren't going to be able to tease out in a trial?
• 14:35
  SPEAKER_00: Absolutely.
• 14:36
  SPEAKER_00: I think that's such an important point.
• 14:38
  SPEAKER_00: Duration is not just duration across the board for all drugs.
• 14:41
  SPEAKER_00: It has to be the right drug and to apply that duration to.
• 14:46
  SPEAKER_00: So, how have you implemented shorter durations for UTI at your institution?
• 14:50
  SPEAKER_01: We're relatively fortunate in that we have pretty broad buy-in of a computer decision support system where the majority of antibiotics administered in our facility are done via this CDSS.
• 15:02
  SPEAKER_01: And so for us, it really was going to our team and saying, you know what, we're gonna move the default duration to seven days.
• 15:09
  SPEAKER_01: We have a brief blurb of text explaining that, you know, if your patient is fredbile, you may consider longer treatment, but the default comes out as seven.
• 15:17
  SPEAKER_01: And so that's what we've done to address it.
• 15:19
  SPEAKER_01: And for the most part, it's gone quite well because I've been hassling all of our providers about trying to enroll patients in the study.
• 15:25
  SPEAKER_01: Most of them are aware that it was going on and were sort of looking forward, like, oh, you finally finished this and got it done.
• 15:30
  SPEAKER_01: So they're happy to happy to participate.
• 15:33
  SPEAKER_01: And yeah, I hope I'm hoping this will be adopted into future guidelines with all the caveats that are there.
• 15:39
  SPEAKER_01: But locally it's been pretty, pretty smooth and uneventful to roll out.
• 15:43
  SPEAKER_00: That's great.
• 15:44
  SPEAKER_00: And you included a comment to how instruct clinicians, but I imagine all the education you did as as you were enrolling really helped with safely implementing this as well.
• 15:55
  SPEAKER_01: I think so.
• 15:56
  SPEAKER_01: I mean, the people that have been around throughout the trial, they've seen, they've listened to you know, research talks in progress, and they've heard this so many times that I think by now they could give the rationale and the results for the trial on their own.
• 16:07
  SPEAKER_01: That's great.
• 16:08
  SPEAKER_00: All right, Dr.
• 16:09
  SPEAKER_00: Holbar, moving on to you.
• 16:11
  SPEAKER_00: What about UTIs and shortening the duration at your institution?
• 16:15
  SPEAKER_00: Have you guys been able to move the needle on the duration for UTIs?
• 16:19
  SPEAKER_02: Yeah, our approach to shortening duration of therapy for UTIs is similar to what I described for pneumonia.
• 16:26
  SPEAKER_02: And it's certainly easier when there are studies that are published, like the one that Dr.
• 16:30
  SPEAKER_02: Traconia led and just described, because the conversation with frontline providers is much more straightforward.
• 16:37
  SPEAKER_02: And I think the fact that these studies are pragmatic and design also really helps us that it's a lot easier to generalize these results to patient populations.
• 16:48
  SPEAKER_02: So we have done similar things in terms of our order sets.
• 16:52
  SPEAKER_02: I think, especially for outpatient management of common infections, clinician decision support tools, and things within the electronic medical record help a lot in setting the default duration for providers.
• 17:06
  SPEAKER_02: And I like that idea of including a brief reinforcement of previously developed educational content to kind of educate on the fly, like at time, at point of care.
• 17:17
  SPEAKER_02: And I think that's a good idea.
• 17:19
  SPEAKER_02: I think, too, this provides a great opportunity again to work with transitions of care pharmacists and others who know when a patient's about to be discharged and then can help verify the duration of therapy they've received already and ensure they don't go home from the hospital with a longer than necessary duration of therapy.
• 17:40
  SPEAKER_00: Absolutely.
• 17:41
  SPEAKER_00: Those are all wonderful points.
• 17:43
  SPEAKER_00: So, do either of you have any final thoughts on either pneumonia or CAP or a duration that we didn't talk about, a different indication.
• 17:52
  SPEAKER_01: I would just comment that I'm getting more and more comfortable defaulting towards the shorter.
• 17:58
  SPEAKER_01: And I also, it when you do one of these trials and you read about all these other results coming up, I'm trying to be better at implementing them because I've recognized that there are places where we're we're having these types of discussions where I'm still finding myself giving a range of treatment duration in my consult notes, saying, you know, go ahead and treat for seven to 14 days.
• 18:20
  SPEAKER_01: And like, oh, wait a minute, like why am I not specifying?
• 18:23
  SPEAKER_01: Like, I did this study, I should be, I should be more firm about what the evidence shows.
• 18:28
  SPEAKER_01: And also in studies, you know, similar with pneumonia.
• 18:31
  SPEAKER_01: So trying to avoid things like ranges in your notes, but rather giving the short duration.
• 18:35
  SPEAKER_01: And you know, you can always leave the caveat that if being slow to respond can consider extending therapy, we'll discuss, but for now, planned duration is X amount of days.
• 18:44
  SPEAKER_00: That's great.
• 18:45
  SPEAKER_00: Yeah, one thing we tell our fellows is to actually give a date as well, because people count differently.
• 18:51
  SPEAKER_00: So sometimes you'll end up with 10 days when you were really meaning for seven, just because of the counting.
• 18:57
  SPEAKER_00: Dr.
• 18:57
  SPEAKER_00: Holabar, how about you?
• 18:59
  SPEAKER_02: Those are both really great points.
• 19:00
  SPEAKER_02: It sounds like what you were putting forth, Dr.
• 19:03
  SPEAKER_02: Traconia, it could be just like a smart phrase that everybody puts in their note.
• 19:07
  SPEAKER_02: But I totally agree that the ranges really do us a disservice.
• 19:11
  SPEAKER_02: And in history, kind of in terms of medical practice, there's been a belief that more is better.
• 19:17
  SPEAKER_02: And so frontline clinicians, when getting those recommendations, will often air towards a longer course of therapy.
• 19:24
  SPEAKER_02: So I like that idea a lot.
• 19:26
  SPEAKER_02: I think the other thing to say is that this, even though we focused on these two syndromes, as we've alluded to, both all of us have.
• 19:34
  SPEAKER_02: There's lots of other data that's coming and has recently been published for other syndromes.
• 19:39
  SPEAKER_02: And so to say that shorter is always better is not right, but shorter is at least as good as longer course of therapy for many common infections.
• 19:48
  SPEAKER_02: So being able to arm our colleagues in internal medicine and other frontline clinicians with this data is really great.
• 19:55
  SPEAKER_02: It's empowering and it's gratifying as a steward because you're not talking about spectrum of activity necessarily.
• 20:02
  SPEAKER_02: You're really giving some concrete information about duration of therapy.
• 20:07
  SPEAKER_02: And as you said, Rebecca, every day counts.
• 20:10
  SPEAKER_00: Absolutely.
• 20:11
  SPEAKER_00: And as you've mentioned several times, I mean, that's the goal is to get the frontline clinician to make the right decisions.
• 20:18
  SPEAKER_00: And there are not enough stewards out there to be right there beside decision makers as they're, you know, going through those critical decisions on antibiotic use.
• 20:26
  SPEAKER_00: And so training more boots on the ground is always a wonderful thing.
• 20:30
  SPEAKER_00: Thank you both.
• 20:31
  SPEAKER_00: This has been such a great conversation.
• 20:33
  SPEAKER_00: It's been a pleasure to learn from you both and kind of hear how you're approaching these durations and how you're implementing stewardship and really engaging the frontline provider and always reflecting back on your own practice as well.
• 20:47
  SPEAKER_00: So thank you, Dr.
• 20:48
  SPEAKER_00: Draconi and Dr.
• 20:49
  SPEAKER_00: Clobar.
• 20:50
  SPEAKER_01: Very much appreciated.
• 20:51
  SPEAKER_01: It was fun to virtually meet both of you and really enjoyed the conversation.
• 20:56
  SPEAKER_02: Agreed.
• 20:57
  SPEAKER_02: Agreed.
• 20:58
  SPEAKER_02: Thank you.
• 20:58
  SPEAKER_00: You can find more educational content like this podcast on Shay's online education center, Learning CE, at www.learningce.shay-online.org.
• 21:11
  SPEAKER_00: This concludes our final episode of the antimicrobial stewardship popery series.
• 21:16
  SPEAKER_00: Thank you for tuning in.