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SHEA Journal Club Spotlight: Key Studies on Antibiotic Therapy & Asymptomatic Bacteriuria · The SHEA Podcast

• 0:08
  SPEAKER_00: Welcome to the Shea Podcast.
• 0:10
  SPEAKER_00: Today's episode of the podcast features members of the Shea Journal Club sharing the work that the Journal Club does and discussing a few of the most standout articles they've reviewed thus far this year.
• 0:21
  SPEAKER_00: All Shea Journal Club write-ups are available to members and non-members on the SHA website.
• 0:26
  SPEAKER_00: Stay tuned after the podcast to hear exciting information about ID Week 2024.
• 0:41
  SPEAKER_03: Thank you for being here.
• 0:43
  SPEAKER_03: And this is the Shea Journal Club on the Shea Podcast.
• 0:47
  SPEAKER_03: Shea Journal Club is one of the groups within Shea, and we meet once a month to discuss relevant literature that's been published in the last month.
• 0:56
  SPEAKER_03: We have a group of about 12 people that come and all bring expertise and review each journal article.
• 1:03
  SPEAKER_03: And today I have Jen and David that are going to also talk about two of the most impactful journal articles that we've had so far this year.
• 1:13
  SPEAKER_03: My name's Hannah Imlay.
• 1:14
  SPEAKER_03: I'm one of the infectious disease doctors at the University of Utah, and I direct our immunocompromise stewardship program, and I'm also the associate medical director of our overall stewardship program.
• 1:25
  SPEAKER_03: And I'm joined by David Kluck and Jen Solar, and I'm going to let them introduce themselves.
• 1:30
  SPEAKER_03: David, you want to go first?
• 1:32
  SPEAKER_02: Happy to.
• 1:33
  SPEAKER_02: So I'm David Kluck.
• 1:34
  SPEAKER_02: I'm an associate professor of pharmacy at East Tennessee State University, Gap and College of Pharmacy, really involved in both stewardship and infection control, maybe in a sequential fashion, and also in a more traditional sense in that I'm still around in with a consult service.
• 1:49
  SPEAKER_02: I feel like a lot of pharmacists and stewardship roles today are doing things remotely.
• 1:54
  SPEAKER_02: So I get to make real-time interventions.
• 1:56
  SPEAKER_02: And I would say that my role in infection control kind of falls under the same umbrella as stewardship and a large health system.
• 2:03
  SPEAKER_02: Those two things kind of walk hand in hand.
• 2:06
  SPEAKER_02: And so stewardship ideas, I think a lot of times arise and ultimately funnel down to infection control practices sometimes.
• 2:13
  SPEAKER_02: So both of those seem to meet together for my practice.
• 2:18
  SPEAKER_04: Hi, I'm Jen Solar.
• 2:20
  SPEAKER_04: I'm an infectious disease doctor at Vanderbilt University Medical Center.
• 2:24
  SPEAKER_04: Recently finished up my Ivy fellowship there a couple of years ago and was fortunate to join the faculty there.
• 2:29
  SPEAKER_04: So in addition to clinical work, I'm also our hospital epidemiologist for Vanderbilt Regional Hospital Facilities, which is three uh different community hospitals that Vanderbilt acquired a couple years back.
• 2:40
  SPEAKER_04: So it's been really interesting to have access to insights for infection prevention practices that we use at the larger academic main hospital and apply that to our community facilities.
• 2:51
  SPEAKER_03: I don't think I realized that I picked our Tennessee members.
• 2:54
  SPEAKER_03: This wasn't supposed to be a Tennessee themed podcast, as far as I know.
• 2:58
  SPEAKER_03: All right.
• 2:59
  SPEAKER_03: David, do you want to talk about your article?
• 3:03
  SPEAKER_02: Yeah, happy to start.
• 3:04
  SPEAKER_02: So my article was published in JAM and Network Open in March of this year.
• 3:08
  SPEAKER_02: Uh, it is bacteremia from a presumed urinary source in hospitalized adults with asymptomatic bacteria.
• 3:15
  SPEAKER_02: So we'll just kind of walk through each of the pieces of the study and the things that I think are important.
• 3:20
  SPEAKER_02: So just to kind of start the objectives of the study, the authors wanted to look at the prevalence and factors associated with bacteremia from a presumed urinary source and in patients with asymptomatic bacteria with and without or without altered mental status, and then estimate antibiotics avoided if a 2% risk of bacteremia threshold was used to prompt empiric treatment.
• 3:45
  SPEAKER_02: So this was a five-year study, retrospective cohort study that had over 11,000 patients from 68 hospitals in the Michigan Hospital Medicine Safety Consortium.
• 3:56
  SPEAKER_02: And they had a nice sort of mix of urban and rural hospitals included in their study.
• 4:02
  SPEAKER_02: Again, five years, and uh the study ended in 2022, and then data were analyzed after that.
• 4:10
  SPEAKER_02: So, primary outcome, um, I think that's important to define to help understand really what the study was trying to look at.
• 4:18
  SPEAKER_02: It had, in my opinion, kind of three different primary outcomes, uh, but looking at the prevalence of bacteremia from a presumed urinary source, and that means positive blood culture with matching organism within three days of urine culture.
• 4:31
  SPEAKER_02: And then to determine factors associated with bacteremia using a multiple logistic regression model.
• 4:37
  SPEAKER_02: And then the secondary outcomes, which I think are kind of overshadowed by the findings of the primary outcomes, which we'll talk about.
• 4:44
  SPEAKER_02: The secondary outcomes include a duration of hospitalization after urine culture, 30-day events that included C def, readmission rate, mortality, uh, andor an emergency room visit.
• 4:55
  SPEAKER_02: So the punchline of this study, and there's a lot of punchlines, a lot of findings that I think are very, very interesting, and certainly centers across the country will be interested in the findings.
• 5:06
  SPEAKER_02: So, among all patients with asymptomatic bacteria, and again, that included over 11,000.
• 5:13
  SPEAKER_02: I always try to think about patient populations in every study as kind of a silhouette.
• 5:18
  SPEAKER_02: So, if you were to randomly pick a patient, uh, who are you likely to find in a study?
• 5:23
  SPEAKER_02: And so in this study, you had really probably a 78-year-old uh Caucasian female unlikely to have an individual and urinary catheter.
• 5:33
  SPEAKER_02: So about 15% of patients in the study had an endwelling urinary catheter, and notably 72%, and so about 8,300 patients received antibiotics in the study, uh, whereas only 1.4% developed bacteremia from a presumed urinary source.
• 5:50
  SPEAKER_02: And so it's a pretty small number comparatively.
• 5:53
  SPEAKER_02: I think one of the things that we'll we'll talk about in just a second, that's a huge takeaway from this study is the fact that they had some risk stratification.
• 6:01
  SPEAKER_02: So among the 44% or so of patients with asymptomatic bacteria who also had altered mental status, the rates of bacteremia were pretty low, and so around 1.8%.
• 6:14
  SPEAKER_02: Um, and I think that's a that's a key takeaway, in my opinion, from this study.
• 6:18
  SPEAKER_02: I mentioned they they used the multiple logistic regression models to look at risk factors.
• 6:23
  SPEAKER_02: And so some of those risk factors were male sex, hypotension greater than two SERS criteria, urinary retention, leukocytosis, pierea, and they defined that as greater than 25 white blood cells, and we're all associated with bacteremia.
• 6:37
  SPEAKER_02: But I will point out that no single factor identified risk for bacteremia exceeding 2%.
• 6:44
  SPEAKER_02: And again, that was their their threshold to use that cutoff.
• 6:48
  SPEAKER_02: Within the study, the authors pointed out that nearly 80%, uh, right at 80% of antimicrobial therapy courses could have been avoided.
• 6:55
  SPEAKER_02: And that was one of the things that they also wanted to look at was antibiotic avoidance.
• 6:59
  SPEAKER_02: To me, one of my favorite.
• 7:01
  SPEAKER_03: That part was like really important to me.
• 7:02
  SPEAKER_03: That that no single risk factor, I think that was really striking.
• 7:06
  SPEAKER_02: Completely agree.
• 7:07
  SPEAKER_02: I I think the thing that I took away from the study that I appreciated the most, and certainly would would entertain your commentary from either of you on this older age, altered mental status, presence of dementia, changing urine color or odor, none of those were associated with bacteremia.
• 7:25
  SPEAKER_02: Now, the key there is it's bacteremia.
• 7:27
  SPEAKER_02: You're not talking about asymptomatic asymptomatic bacteria.
• 7:30
  SPEAKER_02: But many times I've heard this is a justification for we have to start antibiotics.
• 7:35
  SPEAKER_02: We we need to start empiric antibiotics.
• 7:37
  SPEAKER_02: And sometimes it's the caregiver, sometimes it's the patient.
• 7:40
  SPEAKER_02: But I thought those risk factors to me really jumped out from the paper.
• 7:45
  SPEAKER_02: And then the last thing that's sort of buried within the paper, this is not something that they necessarily looked at, but those who received antibiotics and had bacteria received a meeting of 13 days versus six days.
• 7:56
  SPEAKER_02: And so why is that important?
• 7:57
  SPEAKER_02: I I think that we have plenty of data now to show that treatment of bacteremia from a urinary source doesn't need two weeks, but you can get away with seven days.
• 8:08
  SPEAKER_02: And so I I think if that's that's sort of a sign of of uh how the findings from this study might manifest, and I think it's it's slowly.
• 8:19
  SPEAKER_02: So jumping into some limitations really briefly.
• 8:22
  SPEAKER_02: So again, going back to the patient population you're looking at, this this is non-critically ill patients, they're not immunocompromised.
• 8:29
  SPEAKER_02: There was a slew of other exclusion criteria.
• 8:33
  SPEAKER_02: The authors pointed out that it's an it's a retrospective study.
• 8:36
  SPEAKER_02: And so any retrospective study, you're depending on the presence of positive urine culture and documentation of signs and symptoms.
• 8:42
  SPEAKER_02: And I think the last part there is the part that would maybe give me pause because I'm not sure that's always uh well documented.
• 8:50
  SPEAKER_02: And if it is, it would be difficult to find, perhaps.
• 8:53
  SPEAKER_02: The study only captures bacteremia in patients with blood and urine cultures growing the same organism within a three-day infection window.
• 9:00
  SPEAKER_02: So it's possible that they may miss patients for whom blood or urine cultures were obtained, not obtained, were drawn after antibiotic initiation.
• 9:08
  SPEAKER_02: So things to think about when you think about the findings of the study.
• 9:12
  SPEAKER_02: Uh so kind of wrapping up implications and then sort of my prediction or how this impacts practice.
• 9:18
  SPEAKER_02: I think the biggest implication, the biggest takeaway from this study is the fact that there was some risk gratification.
• 9:24
  SPEAKER_02: This has uh long been sort of a data-free zone where you have patients who have dementia or altered mental status, or both.
• 9:33
  SPEAKER_02: And that alone could be the reason that antibiotics are prescribed.
• 9:37
  SPEAKER_02: And I think what this study looks at is okay, if you don't treat those patients, is there is there sequela?
• 9:42
  SPEAKER_02: Is there consequence?
• 9:44
  SPEAKER_02: I think the short answer to that is no, based on their findings.
• 9:48
  SPEAKER_02: And so the takeaway here to me is this provides some reassurance that those patients are not, they don't have a smoldering bacteremia.
• 9:55
  SPEAKER_02: It's pretty uncommon, especially in those who lack evidence of systemic infection.
• 10:01
  SPEAKER_02: The author has kind of mentioned at the very end of the paper that risk calculators might be on the horizon to help personalize who you should treat and who you should not treat.
• 10:11
  SPEAKER_02: Uh, and I think that is a is a key takeaway.
• 10:13
  SPEAKER_02: Last but not least, my prediction for the impact of the findings.
• 10:18
  SPEAKER_02: Unfortunately, I don't think this is going to have the ripple effect in terms of decreasing treatment of asymptomatic asymptomatic bacteria that we're all looking for.
• 10:27
  SPEAKER_02: But I will say I don't think that was the question that they were really seeking to answer.
• 10:32
  SPEAKER_02: I think they were really looking at what is the consequence, as I mentioned, if you don't treat someone's asymptomatic bacteria, do they have or could they have a bacteremia that you missed?
• 10:41
  SPEAKER_02: And I think the answer to that is no, if they don't have any kind of uh evidence of systemic infection.
• 10:46
  SPEAKER_02: Again, I think it's excellent data to support withholding antimicrobial therapy and not resulting in patient harm in the majority of cases.
• 10:54
  SPEAKER_02: And then last but not least, as I've already mentioned, this fills a gap, a needed data gap in an area that I would call data light, or some might say a data-free zone.
• 11:03
  SPEAKER_02: And that is those patients who have uh dementia and or altered mental status.
• 11:08
  SPEAKER_02: So favorite study, good study.
• 11:10
  SPEAKER_02: I think it's one that certainly across the country institutions should be looking at as a way to justify.
• 11:16
  SPEAKER_02: We really need to try to harness asymptomatic bacteria, which I think is uh the treatment of that is rampant across the country.
• 11:24
  SPEAKER_03: Thank you.
• 11:25
  SPEAKER_03: Yeah, I will say, I mean, as a clinician, I think we all have taken care of people who had bacteremia and we like cannot figure out a source.
• 11:33
  SPEAKER_03: They do not appear to have urinary symptoms, and uh, you know, it grows in their urine.
• 11:39
  SPEAKER_03: We sort of say, I guess this is a urinary pathogen that became bacteremia.
• 11:43
  SPEAKER_03: And so we all have lived that experience, but the reverse of finding, you know, finding bacteriuria, I don't have a good risk calculator until this paper of what is the likelihood that these people are actually sneakily bacteremic.
• 11:56
  SPEAKER_03: So I think for my for my practice, this has been very helpful.
• 12:00
  SPEAKER_03: I've actually since publication not that far, not that long ago, I've talked about this paper with several fellows as well.
• 12:08
  SPEAKER_03: Um, because of this, you know, we've all like had this experience of what if this is what if this is going bad?
• 12:14
  SPEAKER_03: But actually putting some numbers to it is really helpful, including in the altered population.
• 12:20
  SPEAKER_03: Jen, any comments?
• 12:22
  SPEAKER_04: I think you probably summed up everything that I felt, but I know I do.
• 12:26
  SPEAKER_04: I'm I'm glad you were able to review this paper.
• 12:28
  SPEAKER_04: This is a great paper.
• 12:30
  SPEAKER_03: Awesome.
• 12:31
  SPEAKER_03: Thank you.
• 12:32
  SPEAKER_03: Jen, you want to talk about your paper?
• 12:33
  SPEAKER_03: Moving on to more gram negatives, presumably.
• 12:37
  SPEAKER_03: More gram negative.
• 12:38
  SPEAKER_04: Definitely more gram negatives.
• 12:40
  SPEAKER_04: All right.
• 12:40
  SPEAKER_04: So I chose identifying effective durations of antibiotic therapy for the treatment of carbapenum resistant interobacterialis bloodship infections by Soto and colleagues.
• 12:50
  SPEAKER_04: This was a study that was published in CID back in January of this year, and it was part of our kind of February roundup of journal articles.
• 12:58
  SPEAKER_04: So overall, this was a multi-center retrospective propensity score-weighted cohort of patients who had carbapenem resistant and terobacterialis bacteremia or CRE bacteremia, who were admitted essentially between January and December of 2019 among 24 different hospitals in the United States.
• 13:17
  SPEAKER_04: And they looked to compare 30-day mortality or recurrent bacteremia between those who received short courses or about seven to 10 days of antibiotics, of active antibiotics versus longer courses, which they defined it as 14 to 21 days of active antibiotic therapy.
• 13:34
  SPEAKER_04: And so what I liked, they had multiple exclusion criteria factors, such as you know, complicated underlying infection that would usually require prolonged antibiotic duration, regardless, like endocarditis, CNS infections.
• 13:46
  SPEAKER_04: But they did require patients to have survived at least one day after antibiotics, which is continued to try and avoid immortal time bias.
• 13:54
  SPEAKER_04: And they also required folks to have received active antibiotics within 72 hours for at least seven days.
• 13:59
  SPEAKER_04: So I'd like that they included that to kind of capture when we were actively starting active therapy instead of just sorting antibiotics altogether.
• 14:07
  SPEAKER_04: As part of their data analysis, they did apply inverse probability of treatment waiting to help account for selection bias that may have impacted the duration of antibiotic treatment selected for certain folks and to kind of help mitigate confounding by indication, where like more severely ill or more medically complex patients would receive prolonged treatment durations compared to their like healthier counterparts.
• 14:29
  SPEAKER_04: A couple of covariates that I really like that they included when creating their propensity scores, which I thought were great, were like severely immune compromised, ICU emission, a couple different scales that might indicate illness severity, bacteria source, source control, use of carapenum, uh, or uh the novel beta-lactam and such.
• 14:46
  SPEAKER_04: And so I think to the meat of this paper, ultimately they had 183 patients that were included in the study, about 36 in their short course arm, and the median ended up being about nine days of therapy for that.
• 14:58
  SPEAKER_04: And then 64% were in the prolonged course arm, and the median ended up being about 14 days for that.
• 15:04
  SPEAKER_04: And overall, um, the authors found that there was no difference in all-cause mortality or recurrent bacteremia within 30 days between the short course antibiotic and the prolonged course antibiotic group within their way to cohort.
• 15:17
  SPEAKER_04: And so a couple of other additional findings, they noted that about 90% of patients had adequate source control, about 35% of the isolates had a carbapenamase gene, all of which were KPC.
• 15:28
  SPEAKER_04: And the most common regiments that were included in the study were ceptazidine, Abibactum, about 41%, muripenum, vabrobactum, about 11%.
• 15:37
  SPEAKER_04: And then essentially the other half was high dose extended infusion, muripenum with or without immunoglycoside, quinolone, or polymexin.
• 15:44
  SPEAKER_04: And so I think just quickly some limitations.
• 15:46
  SPEAKER_04: I think, I mean, the biggest limitations really again kind of come down to this just being a retrospective nature of the studies, but I do think that they did a good job within creating their um exclusion criteria and their design study to try to mitigate some of the problems that go along with retrospective cohort studies and to try and mitigate some of the selection bias that goes along with a study like this.
• 16:08
  SPEAKER_04: And so what I really liked about this study overall is again, I felt the groups were pretty, you know, well matched, weighted, and especially when it came to things like disease severity, they also included important patient groups like immune compromise folks, so like solid organ transplant, neutropenic folks as well.
• 16:23
  SPEAKER_04: And I think it really had us highlight and kind of confirm a lot of what probably most of us in IDER are doing um with regards to treating CRE infections and blood stream infections, but that prior studies looking at GREM negative bacteria needed treatment duration never really fully included in their original investigations.
• 16:41
  SPEAKER_04: And so, you know, when we look at these organisms that have scarier looking resistance patterns, it I think makes a lot of folks feel nervous about wanting to treat longer and need to be a little bit more aggressive, you know, just in case.
• 16:52
  SPEAKER_04: But this is a nice kind of study to reference support shorter durations, even with our CRE bloodstream infections that I think will further help antibiotic stewardship efforts and then kind of trickle down into um hopefully helping our infection prevention programs alike.
• 17:05
  SPEAKER_03: So yeah, that's great.
• 17:07
  SPEAKER_03: Yeah, I I really liked they they sort of emphasized how many CRE infections were recruited into previous randomized trials.
• 17:15
  SPEAKER_03: And it is, it was what was it like less than five?
• 17:18
  SPEAKER_03: Oh yeah, it was something like that.
• 17:20
  SPEAKER_03: Which I hope we never get to a place where we're recruiting a bunch of CRE infections into our RCTs, but we might.
• 17:26
  SPEAKER_03: So until then we have this paper.
• 17:29
  SPEAKER_03: But I like how you summed it up where you know, I think we do we are scared of specific pathogens that appear more resistant, that does not necessarily have implications for virulence and now, you know, does not necessarily have implications for do we need to do more stuff to treat them longer, other than the regular things that we should always be doing, like source control and stuff like that.
• 17:51
  SPEAKER_04: Exactly.
• 17:52
  SPEAKER_04: And I I think too, I think that when they highlighted kind of the, you know, including similar severities of illness, it's really easy to see someone who's ill and an ICU, maybe immune compromised, and again want to treat for a little bit longer than you might actually need to.
• 18:05
  SPEAKER_04: Um so this I think helps support and give a little bit more reassurance to folks, not even just ID, but I think kind of how staff like that shorter, shorter courses would be just as effective.
• 18:16
  SPEAKER_03: Wonderful.
• 18:17
  SPEAKER_03: David, any thoughts or any um follow-up thoughts, Jen?
• 18:22
  SPEAKER_02: I'll just say that, you know, I think in the in the the last iteration of the guidelines that I remember on the IDSA gram negative resistance guidelines, I think there's a sentence in there somewhere that talks about this kind of being another, again, a data-free zone.
• 18:35
  SPEAKER_02: We we just don't have data to say, you know, if it's an ESBL that it warrants extended durations of therapy.
• 18:42
  SPEAKER_02: So I like the paper.
• 18:44
  SPEAKER_02: I think uh it'll probably find its way into those guidelines uh as supportive evidence for for shorter courses.
• 18:51
  SPEAKER_03: And I think like everything in the data-free zone that we talk about in ID, like there's a reason that we have no data, and and often because that those data are hard to collect or that patient population is hard to recruit.
• 19:02
  SPEAKER_03: So yeah, I think when we can have it, we you know uh cherish it.
• 19:07
  SPEAKER_03: Awesome.
• 19:09
  SPEAKER_03: David and Jen, thank you so much for sharing your insights and highlighting these important two studies.
• 19:14
  SPEAKER_03: I had a good time, uh, as I always do.
• 19:17
  SPEAKER_03: Before we sign off, I want to remind all of our listeners that all of the SHA Journal Club meets monthly.
• 19:23
  SPEAKER_03: We also send our write-ups via the Shea listserv, and all of our write-ups are available on the SHA website on the membership page.
• 19:31
  SPEAKER_03: That concludes this episode of the SHA podcast.
• 19:34
  SPEAKER_03: Thank you for tuning in.
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