Hi everyone.

Welcome to Febrile, a cultured podcast about all things infectious diseases.

We use consult questions to dive into ID clinical reasoning, diagnostics and antimicrobial management.

I'm Sara Dong, your host and a Med-Peds ID doc.

Today we have a team joining us from the University of Southern California and LA General Medical Center.

Guiding us will be Hannah Chute, who is a fourth year medical student at Keck School of Medicine at USC, currently applying to internal medicine.

Hi, I am Hannah.

Thank you so much for having us.

Next we have Dr.

Paloma Reta-Impey, who is a first year ID fellow at USC / LA General Medical Center.

Hi, I'm Paloma.

Thanks for having us on.

And lastly, we are joined by Dr.

Brad Spellberg, who is the Chief Medical Officer at the Los Angeles General Medical Center, one of the largest public hospitals in the US.

He staffs internal medicine wards, infectious disease consults, and the antibiotic stewardship service at LA General.

He also maintains an active NIH funded basic science lab that focuses on novel solutions to combating antibiotic resistant infections.

Hi, I'm Brad.

Thanks for hosting this.

Great.

So we ask as everyone's favorite cultured podcast, if you wouldn't mind sharing a little piece of culture, just something non-medical that brings you happiness.

Uh, maybe Hannah, I'll start with you.

Sure.

I thought a lot about this.

Um, I don't know if it's poor form to recommend another podcast.

Um, That's okay.

But something that I've really been, something I've really been enjoying recently is Home Cooking, um, with Samin Nosrat and Hrishikesh Hirway.

It was originally a lockdown era cooking podcast, but, um, they've kept it going over time and it's now just about like food and celebrating small joys.

Um, and it's pretty much a warm hug and audio form.

Highly recommend it.

Excellent.

Love it.

What about you, Paloma?

Hi.

Um, so something that I really enjoy outside of medicine is being in the outdoors and camping.

And I recently got a fantastic opportunity to go out to Joshua Tree National Park with some friends who were visiting.

Um, and we went during the week and it was lovely and a beautiful experience.

And it was just at the tail end of a, a kind of fading moon.

And so there was a lot of really great nighttime photography as well, um, to participate in.

Overall support your national park systems.

What about you, Brad?

My kids and my dog.

Love it.

Um, alright, well I will hand it over to Hannah who's gonna tell us about some cases today.

Yeah, so our first case today is a 58-year-old female.

She has a history of type two diabetes.

Her most recent A1C about eight months ago was 9.3%.

She also has a history of hypertension, osteoarthritis of the hips and right knee.

She's admitted after presenting to the ED from podiatry clinic for worsening foot ulcer and fevers and chills.

She has had diabetes for about 20 years.

She has inconsistent follow up with her primary care doctor due to social factors.

She works long hours in her family restaurant with longer hours recently as her two siblings who previously worked alongside her are now both on dialysis for diabetes related kidney disease.

She's on her feet all day at work.

She first notices a blister at the base of her great toe about six weeks ago.

She's not sure how long that's been present because her arthritis makes it difficult for her to perform her own foot checks.

She initially presented to podiatry clinic a month ago and received local wound care.

She then presented to clinic a week later with worsening ascending erythema.

X-ray at that time showed soft tissue involvement only.

So she was diagnosed with cellulitis and given a one week course of cephalexin.

She took that full course, uh, but her symptoms continued to worsen and her ulcer began to exude purulent fluid, which prompted her to return to her podiatrist once again.

Uh, this time she was sent from clinic to the ED for further evaluation.

Her exam in the ED was notable for 1+ pedal pulses, decreased sensation to pinprick in a glove and stocking distribution, and a one centimeter ulcer on the plantar surface of the right foot at the base of the great toe with erythema ascending to the ankle, no crepitance or fluctuance.

The ulcer probed to bone with associated purulence and abscess.

X-ray was diagnostic of osteomyelitis of the first metatarsal head.

Her wound cultures grew MSSA susceptible to trimethoprim-sulfamethoxazole, doxycycline, levofloxacin, and rifampin.

Her blood cultures are negative.

She undergoes debridement with ortho, but retains some infected bone.

Okay, perfect.

So, um, I'm just gonna give a summary statement for this patient just because there's a couple of, uh, moving pieces in terms of her care.

And then I'll use this as an opportunity to kind of jump into the current guideline recommendations for diabetic foot infections, and, um, talk a little bit more about some of the pertinent recommendations that are applicable to this patient's case.

So summary statement for her is this is a 58-year-old female with a past medical history significant for diabetes, who presented with a six week history of a non-healing diabetic foot ulcer, found to have MSSA diabetic foot osteomyelitis now status post debridement.

However, she has, um, retention of infected bone and is currently on ceftriaxone.

So in terms of the guideline recommendations that exist currently, so we are going to be going off of the 2023 International Working Group of Diabetic Foot and IDSA guidelines on the diagnosis and treatment of diabetes related foot infections.

And this was, um, most recently updated in October of, uh, 2023.

So it's actually, it's celebrating its second birthday today from update.

So kind of pertinent, uh, recommendations in terms of this specific patient's case.

The guidelines do recommend assessing the severity of this infection of a diabetic foot infection using a proposed classification schema, number one through four, with one being uninfected and four being a severe infection with systemic symptoms to describe both the infection itself, uh, plus or minus the presence of osteomyelitis.

And this is going to help to dictate and guide the initial empiric treatment regimen, but also the duration and course that patients would typically receive, um, when treating a diabetic foot infection.

The other main guideline recommendations in regards to once you are able to kind of classify what type of diabetic foot infection this is.

So going back to their proposed classification schema, this patient would fall under either a number three or number four.

Number three being a moderate infection, she's got a deep infection that tracks down into the bone.

Um, you could also classify her as a severe infection based on the fact that she did have systemic manifestations with both, um, fevers and chills prior to presentation.

So just for the sake of this case, I'm gonna go ahead and classify her as a severe infection.

Now from that standpoint, now that we have a classification for her, using our further guideline recommendations.

Um.

The world is kind of our oyster in terms of what they recommend, um, in terms of an initial antibiotic selection and also our duration of therapy.

So in terms of figuring out what antibiotics empirically, we wanna treat a patient with a diabetic foot ulcer.

The guidelines do recommend that any antibiotic that has been shown in randomized controlled studies to treat both patients with diabetes and, uh, skin and soft tissue infections can be used to treat diabetic foot infections.

In this specific patient's case because we are going to classify her as a severe infection, typically we would want to start off with treating her with an IV antibiotic.

Uh, but there is room within these guidelines.

Um.

And it does explicitly recommend that we can at some point, uh, transition her to oral therapy as she progresses throughout her hospital course.

And for patients who have a mild diabetic foot infection.

So this would be, there is a signs of infection or inflammation, but there is no systemic involvement.

The guidelines actually do recommend that you can even start with initial oral therapy and treat these patients in the outpatient setting and not have to, uh, require admission, but based on the fact that this patient has a severe infection in addition to systemic symptoms, definitely warrants admission and, uh, initial treatment with IV antibiotics.

And so moving on from those guidelines, now that we have a bug that we're treating and we're treating MSSA, um, the team started her on ceftriaxone, which I think is a reasonable initial antibiotic for her.

And we can now, as we start to talk about discharge, think about whether we want to go with a PO option or an IV option on discharge.

Because per our guidelines, these are both valid options for her and in the setting as she's clinically improving during her hospital stay.

And then the other things to kind of think about for this is, um, for patients who have severe infection under the guideline recommendations, they do also recommend in addition to starting antibiotics for an obvious infection, that patients with severe or moderate infections undergo a surgical evaluation, whether it be urgent and severe infections or, a little bit later out, um, during a hospital stay if they have a, uh, a moderate in, are more clinically stable.

So she's now hopefully received some level of surgical source control.

Unfortunately, from her case there is some positive bone margins, but based on that, even within the guidelines, they do have recommendations that include positive bone margins versus complete or full debridement with, uh, surgical source control.

And so in a situation like this patient, it's very reasonable because of the fact that she has concurrent osteomyelitis, even though she did, um, have some form of surgical source control that we can go ahead and treat her for a slightly longer course of antibiotics.

Their recommendations within our DFI guidelines are going to be about three weeks for osteomyelitis with retained infected bone or if she were to have dead bone or did not have the opportunity to undergo any surgical debridement.

In those instances, we might want to recommend a longer treatment course, which could be up to six weeks.

But the nice thing about these guideline recommendations is that does not specify that it has to be iv.

She's somebody that we could reasonably treat with a po option on hospital discharge if that was clinically indicated.

And then based off of that, I'll go ahead ahead and hand it over to you, Dr.

Spellberg and your thoughts.

So one of the things that, um, the listeners should take away from the dementia with psychosis that I'm gonna share with you is that I call them "schmuidelines", not guidelines.

And if you were to take an electron microscope, put an electron microscope inside the Hubble Space Telescope.

You still couldn't see how much I care what the guidelines say.

It's that small.

It's not quite zero, but it's super close to zero how much I care what the guidelines say.

'cause what I care about is what the trials say.

Sadly, the  schmuidelines very commonly make recommendations that are either based on no data or low quality data, or on the level of evidence that I call the "because we said so" level of evidence, and I don't think that's how medicine should be practiced.

So I don't care if you call it severe or mild or moderate.

That stuff's all meaningless to me.

The question is, does the patient have bone infection or not?

And the reason that that matters is because there are trials that show that longer durations of therapy is needed for bone infections than for non bone infections.

The bone is not involved, we have randomized controlled trials showing that five to six days is adequate duration of therapy for a soft tissue infection.

Now, interestingly, if bone is involved, the trial situation is more complex.

The largest two randomized control trials that compared duration of therapy for osteomyelitis compared six versus 12 weeks.

One of those was a diabetic foot infection trial.

The other was a vertebral osteo trial, and both showed six weeks is as effective as 12.

So we know you don't need to go more than six weeks for an osteo without prosthetic joint involvement.

There are three smaller trials in the setting of diabetic foot infections that suggest that three to four weeks may be adequate with debridement.

Those are small, 30 to 40 patient trials.

To me, not quite enough for me to hang my hat on.

I certainly do think it's not crazy to give four weeks, maybe three, but I would like a larger trial before I sort of moved in that direction personally.

Um, and then there's the question of IV or PO.

So I'm gonna try to make this as simple as I can.

The bacteria don't actually know the route of administration you use to administer the antibiotic.

It's not like there's bacteria sitting in this poor lady's bone going, well, normally if there was this much antibiotic around, I'd stop growing and die, but you gave the antibiotics orally.

So I simply refuse to stop growing and die.

Those little bugs are smart, but they're not that smart.

Okay, so the only question is, well, I'll say the only two questions.

Do we think we can deliver antibiotic into bone at concentrations necessary to kill bacteria.

And if so, are there clinical data that validate that it works?

And the answer to both of those questions is yes.

There are dozens and dozens of studies where they took patients who had been given oral antibiotics and an hour or two later got a bone biopsy or an amputation, and they ground up the bone and measured the antibiotic levels.

Multiple types of antibiotics can get into bone at levels well above those needed to kill bacteria when the antibiotics were given orally.

And there is an ungodly amount of clinical data now validating that pharmacological hypothesis, including 10 randomized controlled trials of osteomyelitis in which IV only therapy was compared to oral transitional therapy.

In the most recent of those trials, there was no IV lead-in.

Patients were randomized to oral therapy on day one.

In other trials, there may have been 3, 4, 5 days or up to 10 days of IV lead-in.

So the bottom line is there's nothing magical about IV antibiotics.

If the patient could go home, send them home on orals and, and when do you do that?

When they're hemodynamically stable 'cause you ain't discharging the hemodynamically unstable patient.

It doesn't make sense if you're going to take this person to the OR, they're gonna be NPO.

What sense does it make to put them on oral therapy and then make them NPO?

So wait until their surgery is done.

Their gut is working.

If they're vomiting, if they're malabsorbing, that's not gonna make any sense.

If the pathogen is resistant to all oral options, that's not gonna make sense.

And then sadly in the United States, sometimes we can get people housing if we put them on IV antibiotics 'cause a skilled nursing facility will take them.

For an unhoused person, that might be a big deal.

So you put 'em on oral, when they're stable, they don't need a source control procedure, the gut is working, you have a viable option that will kill the bacteria when given orally, and there's no psychosocial or economic reason to provide IV therapy.

If that's on day zero, do it on day zero.

If it's on day nine, do it on day nine.

Great.

Um, thank you so much Paloma and Dr.

Spellberg.

Our next case actually does involve an unhoused patient.

So some of the issues that Dr.

Spellberg just brought up, uh, will likely be relevant for him.

Um, this is a 37-year-old unhoused male who has a history of polysubstance use and multiple prior hospitalizations for SSTIs (skin-soft tissue infections).

He presented with acute onset joint pain and erythema for about three days without any history of recent trauma.

His joint was tapped in the ED and showed 53,000 white blood cells and GPCs on stain.

Blood cultures grew MRSA in four out of four bottles, susceptible to linezolid, trimethoprim sulfamethoxazole, levofloxacin, and rifampin.

Uh, A TTE showed a 0.8 centimeter vegetation on his native tricuspid valve, which was confirmed on a subsequent TEE.

He had no heart failure symptoms.

Only moderate regurgitation was visualized on his echoes, so there was no indication for cardiac surgery in his case.

He endorses alcohol use about three to four beers daily.

Um, occasional cannabis, smoking about once a week, and IV drug use, most recently, two days before his presentation.

He's not currently employed, but previously worked in construction.

Born and raised near Bakersfield, California.

No recent travel or sick contacts.

He has a pet dog at the encampment where he's living.

No surgical history, no known allergies, and he does not take any medications.

He undergoes washout of the knee with ortho and his blood cultures clear by day five.

Um, he is seen by addiction medicine while he's in the hospital and started on methadone.

He's clinically much improved and now would like to leave the hospital.

Um, so I think that this case is example of kind of where we don't have great guideline recommendations in terms of, you know, consensus of opinion, as Dr.

Spellberg had mentioned, due to a lack of really robust trials and evidence to help guide us, with some of these more complicated, um, endocarditis cases.

So I'm just, there's a lot to unpack with the, um, AHA 2015 infectious endocarditis guidelines.

So I'm gonna touch upon some of what I think are pertinent guideline recommendations for a, a more complicated case like this one.

So with this, just a summary statement for this patient.

So we have a 37-year-old male with a history of IV drug use who's presenting with acute, non-traumatic right knee pain and found to have right-sided MRSA infectious endocarditis with septic knee arthritis.

What I'm gonna talk about is gonna be focusing on the recommendations for MRSA endocarditis, but there is a little bit of nuance even within that, which I'm not gonna get into too much, but I'll at least touch on the, the key points for that.

So for the 2015 AHA Infectious Endocarditis guidelines, they recommend initial treatment for MRSA infectious endocarditis of using either, um, IV vancomycin at 15 mgs per kg divided, over Q 12 hours.

Or we have some data that supports the use of daptomycin, typically at higher doses, usually around eight mgs per kg as a reasonable alternative to, uh, vancomycin.

But the dosing has not been formally parsed out through rigorous studies.

Daptomycin has actually been approved for right-sided endocarditis for both MSSA and MRSA, but it has not been approved for left-sided infectious endocarditis, per the FDA.

That being said, this doesn't really apply to this gentleman because he has a right-sided endocarditis.

The guidelines also do say that for certain patients, you do have to select for them, but for patients who have uncomplicated right-sided infectious endocarditis, that does not include MRSA 'cause mrSA is one of their criteria that they use to define a complicated right-sided infectious endocarditis.

In patients with uncomplicated, there is a decent amount of data that supports shorter durations of antibiotic courses, sometimes even as short as two weeks, but typically recommending between two and four weeks.

And there is some data that has been shown over the years, which is not explicitly commented on in the guideline recommendations themselves, but show that there is some option for a transition to PO antibiotics for uncomplicated right-sided infectious endocarditis.

That being said, this patient does not hit those criteria, so, um, that's not really an option for him.

And IV is going to be kind of our initial starting point for this gentleman.

So in terms of the recommended duration per the AHA guidelines for MRSA infectious endocarditis, it is variable and it's going to hinge on whether we think that this is a complicated or an uncomplicated infectious endocarditis.

And so for this gentleman, due to the fact that there is a presumed metastatic site of infection in that septic arthritis of the knee, that would qualify him for what we would consider a complicated infectious endocarditis.

And that would warrant at a minimum six weeks of antibiotic treatment, if not more, depending on the patient's overall clinical response and stability prior to cessation of antibiotic therapy.

Another thing I think is important to touch on that does get talked about a little bit in the guidelines, is the use of OPAT for patients like this.

They say that patients who are at low risk for complications of IE, specifically septic emboli and heart failure, who have, and they specify it, reliable social and home support, easy access to the hospital should complications arise, the ability to have regular visits from home infusion nurses and regular clinician visits to closely monitor clinical status.

These patients should be considered for enrollment in outpatient antibiotic therapy.

They also don't explicitly comment on this, but patients who do have a history of IV drug use that is not a contraindication to doing outpatient therapy for them.

And the guidelines do recommend that patients who do have a history of IV drug use should be referred to a drug use cessation program, whether it be addiction medicine and considered for medication assisted therapy.

Um, and on that note, I will hand it over to Dr.

Spellberg because I know there's a lot to unpack with with this one, and I'm sure you have a lot of thoughts on it.

Um, so I neglected to say for the last case, there is one set of guidelines that I actually believe in 'cause I helped to found the organization that writes them, and it's called Wiki Guidelines.

And the reason that I like Wiki guidelines is that the charter of the organization says you can only make a recommendation if there is reproducible i.e.

more than one prospective controlled study that demonstrates the thing should be done, uh, one of which has to be a randomized controlled trial.

So you only make a recommendation when data demonstrates that it's known to be the right thing.

In the absence of that level of evidence, what Wiki guidelines do is provide a clinical review, a discussion of options of pros and cons of various approaches and overtly highlights disagreements amongst the authors so that people can see where they fall on the spectrum of, of considerations.

Whereas in most typical guidelines, dissenting opinions are shut down and everyone pretends that they agree with what's written even when they don't.

The osteomyelitis Wiki guidelines overtly states that oral therapy is fine, including upfront, which is a direct contradiction to the societal guidelines.

That turns out to be one of only two questions that could be answered by a clear recommendation because of reproducible randomized controlled trials.

The same thing is true for bacteremia and endocarditis.

Okay?

This idea that you need IV therapy for endocarditis, IV is more powerful.

Woo.

No, that's based on nothing.

Well, it's based on historical case series from the 1940s and 1950s with oral sulfa, not trimethoprim-sulfamethoxazole, just sulfa, erythromycin or tetracycline.

I mean, come on guys, we gotta do better than that, right?

We have three randomized controlled trials of oral therapy for endocarditis and a pre-post quasi experimental study from France.

The pre-post quasi experimental study was 170 patients per arm, and it was all Staph aureus and it was mostly left sided.

So, oh, by the way, the second randomized control trial was the Hopkins trial, which was all Staph endocarditis and admittedly mostly right-sided, but all Staph and oral therapy was given upfront on day zero in the ER.

There was no IV lead in.

So let's stop pretending that these guidelines are based on anything other than the "because we said so" level of evidence.

And actually talk about the trial data of which there is a large amount at this point, including POET.

But POET.

I like to quote Mr.

Spock from Star Trek four, or paraphrase him.

POET is the beginning of wisdom, not the end.

There are two other randomized controlled trials, a quasi experimental study, and about 20 observational studies, all of which show the same thing.

Oral therapy is just fine.

Just use the right agents for the right duration.

As far as the duration, I find it hard to believe that the patient with endocarditis from the septic joint doesn't have some osteo in the knee.

I'm sorry.

I'm treating that patient for six weeks 'cause I think they have an osteo.

I don't care about the freaking endocarditis argument.

2, 4, 6.

There's an osteo, very likely I would treat for six weeks.

If you could convince me that there wasn't an osteo and you could convince me, there was no vegetation on the left side, and that would take a lot of convincing.

Okay, maybe I would do four weeks, and that's, again, that's based on, I don't know, I'm admitting, I don't know.

There's no good trials to show us the duration, so let's not pretend that there are.

So that's kind of my take on this situation.

I would be perfectly fine with oral therapy as soon as the patient was hemodynamically stable, we've cleared the blood cultures, their gut is working.

We know we have oral options that will work.

Now is there a reason to put 'em in a SNF (skilled nursing facility) to get 'em housing?

If they do not, if they're literally gonna go back to the street to a tent and they say, can you get me housing?

Yeah, I might put 'em on IV so I could get 'em into a SNF and buy them some time for a social worker to get 'em some interim housing.

But we also have data that patients who are homeless who take oral, oral options will complete their therapy just as frequently as they will with iv.

Here's the other hilarious misnomer.

When we send people home, quote on IV therapy, a nurse comes to the house every day to hang the antibiotics.

That does not happen.

They get home health twice a week.

The IV bags are left in the fridge.

The nurse hooks it up, the pump infuses it.

That patient is on their own for three days till they see that nurse again.

They're no more likely to complete that therapy than they would be if you gave them pills and they won't have a plastic tube in their central vein.

It turns out hominids did not evolve with large plastic tubing in their central veins for six weeks at a time.

It's dangerous.

Stop doing that to people.

Yeah, so that, those are my thoughts.

All right, our last patient, a little bit of a different case.

Uh, this is a 94-year-old woman with history of hypertension, moderate dementia in the setting of Alzheimer's, chronic kidney disease, osteoporosis, and some chronic back pain that's treated with occasional steroid injections.

Uh, she presented with acute on chronic back pain.

Rikers and chills three days after one of those steroid injections.

She was found on MRI to have vertebral osteomyelitis without any epidural abscess noted at the level of that recent steroid injection.

Her blood cultures grew MSSA in 4 out of 4 bottles on hospital day one.

Uh, it was susceptible to linezolid, vancomycin and clindamycin, but resistant to levofloxacin, rifampin.

Two out of four bottles remained positive on hospital day three.

Subsequent cultures were negative.

An average quality TTE was equivocal with potential thickening of the mitral valve.

She was considered a poor candidate for TEE based on her age.

In terms of her surgical history, she had two C-sections 60 years ago.

She just takes Tylenol PRN for back pain.

She lives with her adult daughter, who's her primary caretaker.

The daughter also works full-time.

The patient has been retired for many years, but used to be an elementary school teacher.

She does not use any tobacco, alcohol, or other recreational drugs.

She was born in Taiwan, but has now not left the US in about 30 years, and she has no sick contacts.

All right, so this case is, um, a little bit less of a polarizing case in terms of guideline recommendations and also the ability to both use PO antibiotics and when we might want to transition from IV to po.

With this we're gonna be discussing the 2015 IDSA practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis that was published in July of 2015.

This one we're gonna give a shout out to one of our home institution physicians, um, Dr.

Holtom, who was a expert panel contributor for these guideline recommendations.

They address a couple of topics that I think are helpful to touch on, um, specifically in regards to osteomyelitis and when we should start or stop empiric antibiotic treatment.

So for one of the questions that gets posed is when to start empiric antibiotics in patients who are presenting with concern for vertebral osteo.

So these guidelines recommend that if the patient is not acutely ill and they're clinically stable, they do not have signs of neurologic dysfunction, it is very reasonable to actually withhold antibiotics pending the ability to obtain reliable culture data, ideally from something like a bone biopsy to be able to guide antibiotic treatment.

However, if a patient is sick, they are hemodynamically unstable, they have evidence of worsening neurologic dysfunction.

In those cases, it's very reasonable to treat upfront with an empiric antibiotic regimen.

And it's also worth noting that for a lot of these, uh, recommendations, the evidence supporting the recommendation, as Dr.

Spellberg has mentioned, has actually been fairly low just due to the lack of good randomized control studies regarding this.

So optimal duration for patients when we're treating them for a, uh, native vertebral, um, osteomyelitis is going to be six weeks of antibiotics.

But they do leave room for either IV antibiotics or a highly bioavailable po um, antibiotics.

And this does have a strong recommendation just with low evidence behind it.

They also did touch on, um, when surgery is indicated, and so surgery would be indicated if there's patients who have a progressive focal neurologic deficit, they have significant spinal deformity or spinal instability despite adequate antibiotic treatment, or they have persistent positive blood cultures without an alternative source.

They also use weakening pain, um, as one of the criteria that you should consider surgery, but they advise against pursuing further surgical interventions if only the imaging is worsening, but the patient is continuing to improve clinically.

Um, and then for this patient, for MSSA specific treatment, um, we would want to talk about what options are available to her, and kind of like our initial case presentation with our diabetic foot infection, the world is kind of our oyster.

So, ideally we would like to use either penicillin or cephalosporin, but then we have a lot of other options as well, including both PO and IV options that can include the linezolid, levofloxacin plus rifampin.

You can do clindamycin, you could do vancomycin, or you could do dapto.

And then in terms of the guidelines, they don't give a specific recommendation as to when you can transition from IV to PO therapy, but one thing that they commented on is that a lot of studies have shown that the kind of average time of transition of IV to PO therapy is going to be, um, around two and a half weeks.

So it's very reasonable, just like with our diabetic foot infections to consider, treating patients with po courses of antibiotics being provided that they're bioavailable to continue, uh, treatment courses for osteomyelitis.

And on that note, I will hand it over to Dr.

Spellberg.

So I thank you for giving a shout out to Dr.

Holtom, who has been one of my longest standing colleagues, friends, I mean, we survived COVID together.

Um, he is also a participant in the Wiki guidelines.

And these issues are all discussed in the Wiki guidelines as well.

Both the endocarditis guideline and the osteo guideline.

Um, so let me start with something that's more controversial before I get to the, to me, very simple question of oral duh, um, which is, do you need to get a bone biopsy?

'cause everybody's always, you need to get a bone biopsy.

Well, the ID docs are always, you need to get a bone biopsy.

The hospitalists are always like, do we really?

And the IR people are like, I'm not doing a bone biopsy.

And the ID people are, no, you have to do a bone biopsy.

And then you go round and round and round and they argue with each other and usually you don't get the bone biopsy.

And so if you actually look at the literature, the yield of a bone biopsy isn't very good.

It's kind of sad.

In best case scenario, you'll get a diagnosis about 50 to 60% of the time.

That's not growth of an organism, that's a histopathological diagnosis.

So you're gonna put somebody through a procedure where they're gonna get some sedation and they're gonna have a needle stuck into their spine and half the time it's gonna yield nothing.

Now how does that change management is really the question.

Am I doing this to make myself feel better, in which case my suggestion is take some inhaled ketamine, do some meditation and relax.

Okay?

'cause you're supposed to treat the patient not yourself.

Or am I doing this because it actually helped this patient get better.

And what I have evolved to over the years is it will help this patient get better if I really have no idea what's causing the infection.

And sometimes you'll get these people that have had weeks to months of symptoms and you're like, oh my God, what if it's TB?

What if it's cocci and I put the patient on empiric antibiotics and I'm completely wrong.

Okay.

If it's the last few days worsening back pain, fevers, and you're thinking, this is bacterial, there's nothing wrong with targ-, starting an empiric therapy and seeing if the patient improves.

If I put the patient on Bactrim, with or without rifampin or levo, with or without rifampin, and the next day, their fever that they've had for five straight days is gone and they're like, geez, my back pain is 50% better overnight.

Okay.

They don't have TB, they don't have cocci, right?

You can use empiric therapy and a response to that therapy if you know what you're treating, if there are baseline signs and symptoms of infection that you can follow.

They clearly respond, then I've spared them a biopsy.

It's not changing my management and I'm just gonna keep 'em on therapy and complete a six week course if they don't get better, alright, do I have the right diagnosis?

And now I really do need to argue for a bone biopsy.

I'm sorry, my IR colleague or my neurosurgeon, this patient is now in danger of progression 'cause I don't know what they have and my empiric therapy isn't working and you have a much stronger argument at that point.

So I don't think there's anything wrong in someone where you're highly suspicious that it's bacterial for picking a reasonable empiric regimen and seeing if it makes the patient signs and symptoms better.

Once you know the organism, it becomes pretty easy.

Let me pick something that's gonna cover this organism.

Now, levo rif.

There are good data for, for Staph.

You do need both.

I would not trust levo alone.

You'd need both to prevent resistance emergence.

It's resistant, so that's not an option.

Bactrim is an option.

There's very good data for Bactrim and osteomyelitis.

Some of that data is with rifampin, but not all of it.

Um.

There are less data, considerably less data for oral cephalosporins, but I have become a convert to cefadroxil.

I was very resistant at first, but there are people out there that just loves them some cefadroxil.

When they start talking to you, they'll Jedi mind trick you, man.

They will make you a believer in the cefadroxil.

You know what I'm saying?

And then you're like, all right, and you wincingly try it and then it works.

And you're like, oh, what was I so scared of?

And so we've accumulated, I would say, probably 20 to 30 patients at this point at LA General.

And we're actually in the process of gathering those data up to publish a case series.

There are limited case series available today, but we are have become more comfortable with cefadroxil for MSSA in bone over the last few years.

I don't think it's a crazy thing to do, and I would suggest that at this point you have a shared decision making discussion with the patient.

I think we can do this with an oral.

There's less experience with it.

We have more experience with an iv, but the IV is less safe, and you walk them through the pros and cons and make a shared decision making decision with them, and that's probably how I would care for this patient.

Okay, so thank you for taking the time to discuss these cases with us.

And the reason why we brought these up, um, is to highlight and touch on the fact that, one, our guideline recommendations don't always have great guidance for when we can use oral versus IV options.

And when we are dealing with, especially complex patient populations, much like what we see at our LA General Medical Center, we frequently have to meet patients where they are and don't always have the ability to provide IV antibiotics when patients have, whether social or medical factors that make it challenging for them.

And in those instances, we do have to get creative and find ways that we can use good evidence-based data to help provide appropriate patient care and get patients the treatment that they need for the very complex infections that they have.

So I would just say Paloma for me, um, when I have to get complex and creative is when I can't use oral because oral is my default.

It is clearly less safe to use IV and from 23 randomized controlled trials of bacteremia, osteomyelitis, and endocarditis.

Oral is not less effective than iv.

So sometimes you can't use oral, and that's when I start thinking, all right, I guess I gotta become creative around IVs.

I wanna flip the script.

Oral should be the baseline because it's safer.

And again, we're not here to treat ourselves.

If we wanna treat ourselves, we should take some inhaled ketamine, do some meditation.

I used to say IM benzo, but that hurts.

So just do the inhaled ketamine instead.

Okay, relax.

We're here to treat this patient.

It's not about our anxiety, it's about what's the safest, most effective option for them.

Thanks to our guests for joining Febrile today.

Don't forget to check out the website Febrile podcast.com, where you can find our Consult Notes, which are written supplements of the episodes of links to references, our library of ID infographics, and a link to our merch store.

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Stay safe and I'll see you next time.