Episode 52
52: Phage Hunt
Dr. Saima Aslam gives an introduction to bacteriophage therapy!
Episodes | Consult Notes | Subscribe | Twitter | Merch | febrilepodcast@gmail.com
Transcript
Hello, and welcome to Febrile, a cultured podcast about all things infectious disease.
Sara Dong:We use consult questions to dive into ID clinical reasoning, diagnostics and antimicrobial management.
Sara Dong:I am your host, Sara Dong.
Sara Dong:I am a Med Peds ID fellow.
Sara Dong:I am excited to welcome our guest today, Dr.
Sara Dong:Saima Aslam.
Sara Dong:She is a Professor of Medicine at the Division of Infectious Diseases and Global Public Health at the University of California, San Diego, or U C S D.
Sara Dong:She is a Transplant ID physician and is the Medical Director of the Solid Organ Transplant ID service at U C S D.
Sara Dong:She has also been engaged in phage therapy since 2017 and is the clinical lead at the Center for Innovative Phage Applications and Therapeutics or iPATH.
Sara Dong:She currently has funding through the Cystic Fibrosis Foundation for a pilot study to develop a clinical registry of Burkholderia infected patients with CF and develop an associated bacteriophage library.
Sara Dong:She is also co-investigator in a NIH grant to combat multi-drug resistance through innovative applications, including phage therapy, and she has been involved in multiple transplant related clinical trials, as well as an ongoing study investigating the use of phage lysin for Staph aureus bacteremia.
Sara Dong:Welcome to the show.
Saima Aslam:My pleasure.
Saima Aslam:Thank you very much for the invitation to join.
Sara Dong:Yeah.
Sara Dong:Uh, so before we jump into the case, we always ask one question about whether you could share a piece of culture that brings you joy.
Sara Dong:So something maybe non-medical that you have, uh, had fun with recently?
Saima Aslam:Well, uh, a couple of things recently, , but I guess as recent as yesterday, , um, we had, uh, sort of, what's a religious holiday for us called Eid, e-i-d.
Saima Aslam:And I always have a party the night before in which girls get together and we do henna.
Saima Aslam:And we haven't done that for a couple of you know, years.
Saima Aslam:Yeah.
Saima Aslam:And so Sunday night, uh, I had a bunch of girls and their moms and, oh, it was wonderful.
Saima Aslam:We had lots of henna and I know you can't see it on the podcast, but I got some on my hand.
Sara Dong:Oh, that's awesome.
Saima Aslam:so it, it was, it was a lot of fun.
Sara Dong:Yeah.
Sara Dong:Well, it's always nice to hear about people being able to, to gather and see family again.
Saima Aslam:Yes.
Sara Dong:Um, great.
Sara Dong:So, you know, today's consult question.
Sara Dong:Uh, we have a lung transplant recipient with a multi-drug resistant Pseudomonas and, there is already a little bit of a question about, you know, what therapies are available to us.
Sara Dong:And so I'll give a little bit of a snippet of the case.
Sara Dong:So we have a 55 year old female who has a history of cystic fibrosis and had a bilateral lung transplant in, uh, about.
Sara Dong:Let's say two years ago.
Sara Dong:She's had chronic colonization with resistant Pseudomonas aeruginosa, and her post transplant course has been complicated by a couple things, some primary graft dysfunction.
Sara Dong:Um, she had prolonged mechanical ventilation afterwards because of that.
Sara Dong:And then multiple episodes of this Pseudomonas pneumonia that previously has really only been susceptible to colistin on our testing.
Sara Dong:And so these have led to multiple long courses of antibiotics and not too surprisingly nephro toxicity, which then led to renal failure.
Sara Dong:And then after this, the patient has also developed a component of chronic lung allograft dysfunction, in addition to now needing to be on dialysis.
Sara Dong:And so as the listeners may have guessed by the episode title and the questions we have, and our guest today, we are gonna talk about bacteriophage therapy.
Sara Dong:And so I thought we could start first by having you give us an overview about what is this and, and what types of infections do we think we can use this for?
Saima Aslam:Okay.
Saima Aslam:Well, I was gonna actually start saying that the patient you described, unfortunately, is all too familiar in the transplant ID setting, as well as the cystic fibrosis.
Saima Aslam:So it's important for us to come up with alternatives when we, you know, don't have good antibiotic choices.
Saima Aslam:So in terms of bacteriophages also known as phages.
Saima Aslam:Um, these are viruses that specifically bind to their bacterial host and are internalized, you know, within the bacterial cell.
Saima Aslam:So some are lytic, they go into a lytic cycle in which the virus, once it's in the bacteria, you know, it replicates and basically causes cell lysis.
Saima Aslam:Um, You know, and thus the virions are released and they go in infect other bacteria.
Saima Aslam:And usually when we talk about phage therapy, we're talking about lytic viruses.
Saima Aslam:Uh, you can also have lysogenic phages as well, that go in and integrate within the host genome, um, and you know, can pass on from within the bacterial progeny.
Saima Aslam:And that's quite common as well.
Saima Aslam:So phages were initially discovered in the pre antibiotic era, um, within the early 1900.
Saima Aslam:Uh, both within France and England.
Saima Aslam:And at that time, you know, the viral structures were not known, but that antibacterial effect was known, which is where the name comes from, which is to eat bacteria or bacteriophage.
Saima Aslam:At that time, the sort of specificity of phage therapy was, uh, noted.
Saima Aslam:And so there were different sort of phage preparations for GI upset or GI illnesses and different ones for coryza or, you know, respiratory infections.
Saima Aslam:So that distinction, you know, was there.
Saima Aslam:Um, once antibiotics or penicillin, you know, came along was sort of, I think all of us, at least within Western medicine kind of went down that road.
Saima Aslam:Um, and we've, you know, had more and more antibiotics.
Saima Aslam:Uh, and we sort of didn't go back to phage.
Saima Aslam:Phage therapy has existed in some form since then, actually within Eastern Europe in particular, as well as Russia.
Saima Aslam:There's not a lot published about that experience.
Saima Aslam:So I'm not sure how effective or not it.
Saima Aslam:Uh, but in these countries, phage has traditionally been available sort of over the counter, also sort of within a syndrome, specific formulation.
Saima Aslam:But as far as I know, it's never been used intravenously and these are all oral preparations.
Saima Aslam:So in 2016 at U C S D one of our faculty members actually developed a highly drug resistant Acinetobacter baumanii infection.
Saima Aslam:So pancreatic abscess, you know, multiple abdominal abscesses at some point septic shock, et cetera.
Saima Aslam:Uh, and this was an Acinetobacter resistant to everything.
Saima Aslam:So his wife, uh, Dr.
Saima Aslam:Stephanie Strathdee the, um, and one of our I, our previous ID division chair, Dr.
Saima Aslam:Chip Schooley collaborated in, sort of going down this route of phage therapy and they reached out to a variety of different collaborators, including the Navy and certain industry and treated him with intravenous phage as well as phage within the abdominal abscesses.
Saima Aslam:And he, you know, he walked out of that ICU.
Saima Aslam:Um, and I think that really was an eye opener for us.
Saima Aslam:Um, that case, you know, was written up and widely publicized.
Saima Aslam:And Stephanie wrote a book about it as well.
Saima Aslam:From that case, then we sort of moved on now, you know, to having what we call iPATH or Center for Innovative Phage Application and Therapeutics at U C S D.
Saima Aslam:And this was started in 2018.
Saima Aslam:Um, and we've been treating patients with phage therapy both locally within U C S D, but I also have patients that actually fly in or drive in from other cities or states to get phage as well.
Saima Aslam:So you asked, you know, I guess how it kind of adds into our antibiotics or, you know, how are we using it?
Saima Aslam:So at the moment, one, you know, it's important to know it's experimental.
Saima Aslam:Um, and so each case that we treat on a compassionate use basis, we do undergo, you know, a review by the FDA, uh, and receive what's called an E I N D before we proceed, because it's experimental and it's not widely available.
Saima Aslam:There's a lot of delay in, you know, finding a patient, we think that may benefit to actually finding phage to actually manufacturing, to then getting approval and then treating patient.
Saima Aslam:And that can be anywhere from weeks to months.
Saima Aslam:Um, I had one patient that I started the process and treated a year later uh, and part of that delay was actually, you know, then we had a pandemic, right.
Saima Aslam:so that certainly added to that one year, but.
Saima Aslam:When we're talk.
Saima Aslam:When I talk to other physicians, um, as well as patients, you know, we sort of have this discussion, is the patient one, do we think phage will help this patient?
Saima Aslam:And I think at the moment we're still learning.
Saima Aslam:Um, and I think it's important.
Saima Aslam:It's important to sort of have that discussion with the patient two.
Saima Aslam:Um, at times some people that I assess have so many things that are adding into them being critically ill or severely ill, that the MDR organism is sort of the tip of the iceberg.
Saima Aslam:And even if we get rid of it, their underlying lung disease, for example, from severe COVID, you know, is not going to get better because we got rid of the MDR Acinetobacter.
Saima Aslam:So I think that's the cert and sometimes it's tricky, but I think that's an important consideration when we assess patients for experimental therapies so that's sort of step one for, you know, in patients that may benefit, I think definitely are those that have highly multidrug resistant organisms.
Saima Aslam:Um, so sort of, you know, the lung transplant patient in case, uh, you talked about, um, or those that have not tolerated antibiotics.
Saima Aslam:They may be that, you know, it's susceptible to Cipro, but the patient gets anaphylaxis, right?
Saima Aslam:So that's not the best drug for them.
Saima Aslam:Uh, it's also helpful for certain niche sort of issues like biofilm based infections, where we may have an MSSA.
Saima Aslam:You know, prosthetic joint infection, but it's persistent despite current standard of care, which is, you know, two step I&D um, you know, replacing the joint, et cetera.
Saima Aslam:Um, so some of these cases as well, I, I think are indications for phage therapy as a rescue.
Saima Aslam:So at this point, because we're still learning, um, , you know, I don't think it should be the first thing we think of when we see a patient.
Saima Aslam:Right.
Saima Aslam:it needs to be, they've already gone through a lot and now we're considering experimental therapy.
Saima Aslam:The other thing I think is important is there's been a lot of, you know, P press, um, or a lot of, um, discussion about all these wonderful cases, including the first case at U C S D.
Saima Aslam:You know, responded very well.
Saima Aslam:Unfortunately, there are also cases that have not responded to phage therapy.
Saima Aslam:And so I think it's important to sort of publish those.
Saima Aslam:So people have more of a nuanced idea of how phage, you know, works or does not.
Saima Aslam:Um, so that patients also have a realistic understanding of, you know, what they're undertaking.
Sara Dong:Yeah.
Sara Dong:And I love how you went through that timeline and a little bit of the history, cuz that's not something, I didn't know until recently that, uh, there was as much history, I knew that phage had been around for a while, but the way that it had been used in Europe, I don't think I really had any sense of that.
Sara Dong:Um, and we'll definitely put a link to, uh, Stephanie's book The Perfect Predator, which I think is good reading for anyone an ID.
Saima Aslam:Yeah.
Saima Aslam:Yeah.
Saima Aslam:We also have actually several patient interviews on our iPATH website that they talk about their experience, including one of my patients who speaks Spanish.
Sara Dong:Oh, awesome.
Sara Dong:Okay.
Sara Dong:So we'll put a link to that too.
Sara Dong:All right.
Sara Dong:And so.
Sara Dong:We call up a friend like you, cuz let's say we're getting to sort of a salvage point for our patients and you've hinted a little bit at this, but what are as a fellow, what do we have to be thinking about as far as the steps and data that we need to collect to help identify whether or not this therapy could be, could be, even be considered for the patient that you're
Sara Dong:seeing.
Saima Aslam:So I think whenever as a clinician, we're seeing a patient and we think, Hmm, maybe we could consider phage therapy in this.
Saima Aslam:Step one is really saving the patient's isolate.
Saima Aslam:So calling your microlab and saying, please, can you hold on to this.
Saima Aslam:If there are other isolates from that same patient as we go along, or maybe there's some previous, we need to hold onto all of those, cuz we need the actual bacteria so that we can do susceptibility testing in vitro, uh, looking for phage that may act against that organism.
Saima Aslam:And sometimes we get calls and people talk about their patients, but you know, it's like a week later and the isolates were thrown out.
Saima Aslam:So then that adds into some more delay because then we wait for further positive culture.
Sara Dong:Yeah.
Sara Dong:And then I know that there is sort of two ways to determine if a phage would be susceptible.
Sara Dong:And I think also that raises the question of how do we think about resistance in phage therapy?
Sara Dong:Are there things that we need to consider to sort of counteract the risk of resistance?
Sara Dong:Can you tell us a little bit about that?
Saima Aslam:Yes.
Saima Aslam:So in terms of susceptibility testing, as you said, there's sort of two main ways.
Saima Aslam:One is sort of regular agar plates.
Saima Aslam:And we look for basically, uh, plaques, um, you know, clearings within that bacterial carpet in which phage has, you know, exerted lytic activity.
Saima Aslam:There's also something similar to a time kill curve that can be done.
Saima Aslam:And that also gives you an idea of susceptibility.
Saima Aslam:But what I wanna point out is currently there's no information truly linking what we see in vitro in terms of susceptibility to clinical outcome.
Saima Aslam:So even though we sort of think of them like phages, or like by antibiotics or, you know, within that framework, we don't know if that's actually the right framework to think about it.
Saima Aslam:Um, and then also.
Saima Aslam:We have phages and we have a patient's bacteria and we do both the agar plate and what's called the biolog.
Saima Aslam:Um, or that, you know, time kill type test.
Saima Aslam:Sometimes they're actually not even, I mean, there's incongruity between them.
Saima Aslam:And so it's susceptible in one and not on the other.
Saima Aslam:So we don't know actually, which is the better test.
Saima Aslam:Um, and there is ongoing investigation to sort of figure that out so that we have more of a uniform way of saying, okay, well, you know, this phage is going to kill a certain patient's, you know, bacterial isolate.
Saima Aslam:So I, I think that's important to know upfront.
Saima Aslam:It's not as clear cut or well defined as it is for antibiotic.
Saima Aslam:And because it's only recently that we've started using these for patients.
Saima Aslam:There's a lot of ongoing investigation to actually understand that.
Saima Aslam:And I think some of our failures may be related to the fact that it looks susceptible, you know, on a plaque assay, but perhaps that doesn't translate well to clinical medicine.
Saima Aslam:So, so that's something that is being investigated.
Saima Aslam:Um, but say we do start off with a phage that is susceptible and we start using it to treat a patient generally so far, especially for gram negative infections.
Saima Aslam:Um, most, most, uh, people would use a combination of phages, not just one.
Saima Aslam:Usually you want a combination of a few phages that have different receptors for attaching to a certain organism so that if the bacteria does develop, um, resistance and there's sort of a variety of mechanisms that, that it can do that, uh, there's still other phages that can sort of, you know, still kill the bacteria.
Saima Aslam:So we don't always see phage resistance or development of resistance.
Saima Aslam:In my case, I've treated about 19 patients now with a variety of different organisms and I've noticed the issue more so in the setting of pseudomonas.
Saima Aslam:And I haven't really seen that in Staph aureus.
Saima Aslam:So I think as we're learning more, we'll sort of learn more in terms of,
Saima Aslam:is it a particular phage and bacterial interaction that is more susceptible to development of resistance?
Saima Aslam:Or is it if we target a specific, you know, um, receptor or mechanism that that's more susceptible to resistance.
Saima Aslam:So that's not really well known at this time, you know, in terms of patient care.
Saima Aslam:I think there's a lot that's known in vitro, but we're not sure right now how that translates into how we treat a patient.
Saima Aslam:so for Staph aureus infections, I've used a single phage successfully and there was no resistance.
Saima Aslam:And, you know, at times we don't see that with the Acinetobacter or Pseudomonas, for example.
Sara Dong:Yeah.
Sara Dong:Well, I'll take us back to our example case and say, you know, this patient ultimately, who I have structured off of one of the published cases, um, received three week course of both IV and nebulized phage cocktail, um, but also had ongoing systemic antibiotics with piperacillin-tazobactam and colistin and around the two week mark, she starts to have some decreased inflammation with, uh, decrease in secretions, um, noted on bronchoscopy.
Sara Dong:And so the concomitant antibiotics were stopped about three weeks after the phage therapy was started.
Sara Dong:And around that time on day 21, the BAL culture start to show some non Pseudomonas bacterial species suggesting that maybe there's a reestablishment of a, of a different respiratory flora.
Sara Dong:This therapy is, is so cool and interesting, but I, I think you've started to allude to this, but I wanna make sure that we give pause for what are the challenges.
Sara Dong:And there's a lot of unanswered questions that you've already mentioned, but what are some of these challenges in how we use phages that we should think about as research questions moving forward.
Sara Dong:And, you know, I think, any, any other sort of limitations that you think would be good for us to keep in mind?
Saima Aslam:Right.
Saima Aslam:I have to say this case sounds very familiar or it sounds like a,
Sara Dong:I don't have a good example.
Sara Dong:yeah.
Sara Dong:I merged details together.
Saima Aslam:Yes, no worries.
Saima Aslam:Um, So, yes, several points.
Saima Aslam:One, especially when we first started a few years ago, because it was so new and because we were treating active infections, the FDA would only allow us to use phage in addition to standard of care, which would be antibiotics.
Saima Aslam:And so it is, it's difficult to piece out, especially when you sort of look back at recent published cases, that did the patient get better because we added phage or maybe they would've gone better already if we continued or is it the combination?
Saima Aslam:So, um, in terms of combinations, there is now a lot of interest in when we do phage susceptibility testing to actually look for synergy testing with specific antibiotics as well.
Saima Aslam:Um, and see if there is actually a synergistic combination and then we would want to use that combination.
Saima Aslam:Um, and you know, and that would lead to greater cell lysis or bacterial lysis than either alone.
Saima Aslam:That doesn't always happen.
Saima Aslam:Uh, occasionally they can actually be antagonism as well.
Saima Aslam:So it's nice to do the in vitro work first, before we go ahead and start treating your patient.
Saima Aslam:um, what I've started doing now, so sort of to try to figure out, is it really the phage that is helping a patient versus the combination or versus, you know, a tincture of time?
Saima Aslam:Um, I've started treating a few patients with phage alone.
Saima Aslam:Um, but these are patients that are not acutely infected, meaning maybe they have a positive culture, but it's not an indication to treat them with antibiotic.
Saima Aslam:So, for example, in the setting of kidney transplant, you know, unfortunately patients tend to have recurrent urinary tract infections.
Saima Aslam:And usually in my practice, I've seen that it's the same bug for each patient that comes back again.
Saima Aslam:And again, whether it's an ESBL E coli or Klebsiella, so I've now treated a couple of patients, um, with phage alone when they're not sick, you know, from that infection, but they may have asymptomatic bacteriuria or they have,
Saima Aslam:you know, it's within their GI tract cuz that's where the organism is coming from and see if we can actually get rid of that colonization.
Saima Aslam:So I have seen some success in that and we do have hopefully a paper coming out, uh, that sort of goes through the details, but I, I think there are different ways.
Saima Aslam:of looking at how we can use phage depending on what clinical situation we're sort of trying to alter.
Saima Aslam:And so I think for sure, in the setting of an acute infection, we probably would always treat with phage and antibiotic, unless, you know, there's clinical trial evidence showing it's safe and fine to just give phage alone, but it's always hard to take away standard of care, but, you know, we can add something on to that.
Sara Dong:And is, can I ask one question?
Sara Dong:We've mentioned a couple that I know that there are phage.
Sara Dong:You can do different routes of administration, whether it's IV or inhaled and back, it sounds like had oral previously, how do you, how do you think about that and use that?
Sara Dong:Is it just, it's hard cuz I know we're not really relying on a ton of prior experience, but is there anything that can help you decide on, on which formulation might be.
Sara Dong:Best.
Saima Aslam:So the issue with oral formulations is that phage are actually inactivated by a gastric pH.
Saima Aslam:And so there are now ongoing studies looking at oral phage, but actually specially formulated so actually gets down to the lower intestine I see.
Saima Aslam:Or, um, sort of, you know, an enema uh, way of delivering it.
Saima Aslam:So in terms of how I would use in terms of administration, as you know, step one is what are we treating?
Saima Aslam:Is this a pneumonia?
Saima Aslam:Is this, you know, prosthetic joint infection, et cetera.
Saima Aslam:There's been experience using phage intravenously, for sure.
Saima Aslam:And in some of the patients, especially the early ones I treated with the pneumonia pace patient, you mentioned, we actually would treat it with IV alone, got BAL samples to see if the IV phage actually made it to the lung and it did.
Saima Aslam:And then we also later on treated with, you know, nebulized alone and it still got there in good concentration.
Saima Aslam:So I think so that's one part and.
Saima Aslam:and so, so different administration ways that have been, uh, published, include the intravenous route, nebulization, uh, topical.
Saima Aslam:So maybe for burn wounds, for example, or a driveline, an L V A D driveline infection.
Saima Aslam:That's, you know, superficial as well as rectal instillation uh, oral, we talked about and sort of issues with that.
Saima Aslam:And then also when I have patients with an LVAD infection, for example, or peach prosthetic joint infection, intraop installation of phage directly at that site of infection.
Saima Aslam:So all these different ways have been tried.
Saima Aslam:I don't think we know what is better, um, or.
Saima Aslam:You know, me are all of them equivalent or not.
Saima Aslam:I don't know.
Saima Aslam:Uh, most of my patients, I have treated intravenously.
Saima Aslam:One of the issues with nebulized phage is that the nebulization process may actually, um, actually disrupt the phage and it sort of just kills them.
Saima Aslam:And I had that for one of my patients that I wanted to do nebulize, but actually did in vitro testing before.
Saima Aslam:And realized that the nebulization process basically killed off the phage.
Saima Aslam:So that patient, even though it was a pneumonia, I was treating, we just treated intravenously and the patient has responded to treatment.
Saima Aslam:Yeah.
Saima Aslam:So, yeah, I, I think one of the issues with phage, again, most of us, we think within our antibiotic framework, but all these phages are different.
Saima Aslam:So they're like 11, you know, more than 11 different phage families.
Saima Aslam:Um, and they're not actually all interchangeable.
Saima Aslam:And I think some of the things we're learning is that specific interactions may actually be very specific to phage and, and
Saima Aslam:bacteria.
Sara Dong:And then I think one thing that we can also end on that we haven't necessarily focused on is how safe these are.
Sara Dong:And do we need to think about impact on, uh, things that we don't expect other than the infection that we're treat?
Saima Aslam:Yeah, no, I think that's a really important consideration.
Saima Aslam:Um, especially within the regulatory framework, the FDA.
Saima Aslam:Um, at least for E I N Ds has really prioritized safety of each patient, given that this is experimental.
Saima Aslam:So, you know, I started off saying it's been around for a hundred years, but all, all, most of that experience is oral.
Saima Aslam:So we don't actually have that much published experience in terms of intravenous or nebulized, et C.
Saima Aslam:But in general, I think it's quite safe, phages, you know, they're not infecting human cells, so they're basically going to the bacteria and lysing the bacteria.
Saima Aslam:So we're not really worried about, you know, uh, tubular interstitial nephritis, for example.
Saima Aslam:Um, so in general, it's safe, uh, things that we look at.
Saima Aslam:When we develop phage to treat a patient, it's grown within a bacterial host.
Saima Aslam:So when they develop their filtrates, um, there can actually be endotoxins.
Saima Aslam:It's very important to sort of get rid of the endotoxin and have, you know, and make sure it's, it's sterile, especially when we're going to use it intravenous.
Saima Aslam:So that's one safety aspect and in general, that has not been an issue at all.
Saima Aslam:Cuz we have great ways of getting rid of endotoxin within a phage preparation and we have great ways of ensuring stability.
Saima Aslam:So that really hasn't been an issue, but it's something you always that's sort of step one in terms of safety.
Saima Aslam:For patients that I treat, I always get baselines for a CBC, you know, CMP and inflammatory markers.
Saima Aslam:And I do them weekly.
Saima Aslam:In general, we'll see, inflammatory markers go down.
Saima Aslam:There've been other studies that sh you know, show that actually increase, and maybe that's related to rapid bacterial lysis.
Saima Aslam:So one thing to always to think about is the bacterial burden in a patient.
Saima Aslam:And if we're giving very active phage, uh, especially for example, in a biofilm infection, can that lead to bacteremia or if we have a CF patient, that's got all kinds of pseudomonas and other organisms within their lungs, and we're targeting a very specific pseudomonas, will it allow, you know, maybe more pathogenic organisms to take its place.
Saima Aslam:So I think these are real considerations.
Saima Aslam:And I think, you know, as we learn more we'll know more, uh, but these are things I always talk about to my patients, as well as to other consulting physicians and actually for a couple of my L V a D patients I've seen that what they were not bacteremic at baseline, but once I started treating them with phage within five to seven days, uh, two of them actually developed pseudomonas bacteremia.
Saima Aslam:It was still susceptible to phage in vitro, but these, uh, organisms had different antibiotic susceptibility profiles than what we started off with.
Saima Aslam:So, you know, just within a week and you change the antibiotic, you keep the phage going.
Saima Aslam:Um, and that was okay, but just to think about cuz these were both actually outpatients, one person had no symptoms and we were like, wow, his bacteremic we admitted him, but one of them actually developed septic shock.
Saima Aslam:So, so it's not, so I think it's not so much the phage itself.
Saima Aslam:It's sort of how we're using it and in what sort of host milieu we're using it, uh, that we need to be careful about.
Sara Dong:Yeah.
Sara Dong:And for just thinking about patient access, or I guess you could say patient and clinician access to phage, do most patients have to travel to a center that has this, or are they working collaboratively and getting it phage therapy shipped to them and sample shipped back and forth.
Sara Dong:And I think in that latter scenario, how are there challenges with storing and shipping materials?
Sara Dong:I suspect the answer is yes.
Saima Aslam:Yeah.
Saima Aslam:So I think part of it is if we are talking about a center that's sort of academic, they have, you know, an IRB, they have a research laboratory that can make dilution of phage.
Saima Aslam:So in those places we've certainly help, you know, help teams in developing protocols, their IRB consent form, et cetera, so that patient can get phage where they normally get treatment.
Saima Aslam:Um, I've also had some patients that are in either a rural area or in a private practice setting where it's difficult really to have, you know, the background needed in terms of oversight and research experience, um, to be able to do testing.
Saima Aslam:So some of those we've then.
Saima Aslam:Either.
Saima Aslam:I mean, I've had a couple that came down to San Diego, but again, you know, they were able to do that.
Saima Aslam:Obviously that's expensive for somebody to fly out, you know, fly in here and stay here for a few weeks.
Saima Aslam:Um, but also there are now many places actually.
Saima Aslam:And again, these usually within the academic setting, uh, that are able to provide phage locally to their patient.
Saima Aslam:So at iPath we worked with many centers, uh, and many physicians to sort of make that happen.
Saima Aslam:. Sara Dong: Yeah, well, I always leave it open one last time at the end, for anything else that you think fellow or an ID clinician who's not as familiar with phage therapy should know as closing thoughts.
Saima Aslam:I think the key is, is to really think about phage.
Saima Aslam:So, and to think about it early and not when they're critically ill in the ICU, when two.
Saima Aslam:Because in that setting, we're not gonna be able to get phage in time for that patient.
Saima Aslam:So the time to think about phage is when you see drug-resistant organism or, you know, there's a biofilm based infection, whether it's aortic graft or an L V a D we start saving isolates, start that conversation with the patient, with iPath, you know, or other phage therapy centers.
Saima Aslam:Um, so.
Saima Aslam:You have that lead time to find phage and try to get it to the patient.
Saima Aslam:But many times we worked, you know, Physicians and patients, and it's too late to really help the patient or by the time we find the phage, you know, unfortunately the patient has already passed.
Saima Aslam:So time is of the essence at the moment.
Sara Dong:Yeah.
Sara Dong:Um, well thank you again so much for coming on the show and teaching us about this.
Sara Dong:And I think everyone is looking forward to, to seeing more about the cases.
Saima Aslam:Okay.
Saima Aslam:Awesome.
Saima Aslam:Thank you.
Sara Dong:Thanks for listening everyone.
Sara Dong:This is just scratching the surface on a pretty big topic.
Sara Dong:So we'll have tons of references available on the Consult Notes, which are written complements of the show with links to references available on our website febrilepodcast.com.
Sara Dong:You will also find the library of ID infographics and a link to our merch store on the website.
Sara Dong:Please reach out if you have any suggestions for future shows or wanna be more involved with Febrile.
Sara Dong:Thanks for listening.
