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Nav: Hello and welcome back to Communicable, the podcast brought to you by CMI communications estimates, open access journal, covering infectious diseases and clinical microbiology. My name is Navaneeth Narayanan. I'm a clinical associate professor and ID pharmacist at Rutgers University in New Jersey in the United States, and an associate editor at CMI Comms.

I'm joined by my co-host Thomas Tangden, a fellow editor at CMI Comms. Thomas is a professor and senior consultant of infectious diseases at Uppsala university in Sweden, and is part of an expert group authoring ESCMID's treatment guidelines for MDR gram-negative infections.

Thomas: It's a pleasure to be here,

Nav: Today the topic is antimicrobial resistance and conflict in crisis zones, which unfortunately has become. More common in our world as, geopolitical tensions and conflicts reach a boiling point. We're really grateful to have three expert guests with us today.  Our first is Dr. Aula Abbara She's a consultant in infectious diseases and acute medicine at Imperial NHS Healthcare Trust and an honorary senior clinical lecture and infectious diseases. She's also an infectious diseases and malaria advisor to MSF Amsterdam. She's currently undertaking an NIHR MCR funded CARP fellowship on antimicrobial resistance and displacement.

She is a co-founder of the Syria Public Health Network and has been studying AMR and conflict zones, particularly Syria over the last few years. Aula, welcome to
Communicable.

Aula: Thank you very much, and great to be here.

Thomas: Our second guest is Guido Granata. Who is an infectious disease consultant and researcher at the National Institute for Infectious Disease, Lazzaro Spallanzani (IRCCS). His focus is on prospective observational and interventional studies on AMR and c diff infections.

He has published articles regarding the relationship of war and AMR. Welcome, [00:02:00] Guido.

Guido: It's a great pleasure to be here, to this talk. the topic is really near to my heart.

Nav: And lastly, we're joined by Tuomas Aro, an internal medicine physician and resident in infectious diseases at Helsinki University Hospital in Finland, and a current PhD candidate studying multi-drug resistant bacteria among refugees and migrants.

He also serves on the steering committee of the Trainee Association of ESCMID. Welcome, Tuomas.

Tuomas: Hi, everyone, and greetings from Cold and Dark Finland, and thank you so much for having me. I'm a huge fan of this podcast, so it's a real honor to be here.

Nav: It's real honor to have all three of you here.

I mean, the expertise that you bring, is, quite astounding, and on that note, we always like to get started with the Get to Know You question. What inspired you to do the work that you do in this space.

I think it's, extremely important, and it also has a bit of a niche, and it would be really lovely to hear about your experience and understand why you do the work that you do. So, Aula, why don't you start

Aula: thank you very much, nav. my family [00:03:00] heritage is Syrian and since the onset of the revolution and then escalation into wholescale conflict from 2011, 2012 onwards, I came more and more involved in the humanitarian response in Syria, particularly to the northern areas.

And I was trying to respond, as a clinician at that time, an infectious diseases, trainee in London. And I became more involved in things around antimicrobial stewardship, antibiotic protocols, supporting the facilities on the Turkey side of the Syria Turkey border in terms of infection, prevention and control.

and I continued that work over years. , I was fortunate enough to meet some remarkable colleagues who were trying, and I think this was 2016 or 2017. Starting to have conversations around how do we take the conversation of AMR in conflict settings, in their complexity forward.

And that's when I met Ghassan Abu-Sittah a foremost trauma surgeon,, who's worked around the world, but particularly, and most recently in Gaza, Omar Dewachi and anthropologist, currently at Rutgers University [00:04:00] Vin-Kim Nguyen, who split,. between Canada and Switzerland. And they invited me to start working with their group because they were starting research on AMR and conflict settings.

And so since then I've continued the work on Syria, which is obviously escalated in terms of the conflict intensity until the fall of the regime in December of last year. But of course, what we've seen in this particular early recovery period, and I won't call it a post-conflict period, because there is still areas of conflict at the moment.

The issues that we face around antimicrobial resistance remain quite profound. so that's the story of how I was fortunate enough to meet some remarkable people and be able to engage in this space.

Thank you, Aula. We're quite lucky to have your experience and I'm very much looking forward to hearing that.

Nav: Guido, would you like to go next?

Guido: Thank you. Nav my primary source of inspiration was my desire to better understand the interactions between bacteria, bacterial infections, and their hosts human beings. I have always been fascinated by this topic since [00:05:00] I graduated from medical school, and this led me to become a clinical, consultant in infection diseases.

alongside this, shortly after beginning my specialization and working on the hospital ward, I realized that antibiotic resistance and infection control are crucial, in modern medicine.

Guido: And, this phenomena are constantly evolving. And the idea of studying antibiotic resistant in armed conflict emerged from discussions with colleagues, particularly. some Swedish colleagues And when we talked about the conflict in Ukraine and the patient we had treated the would be transferred from conflict zones, we found that there, were.

Multi-drug resistance, bacterial infections, and also pan resistant bacterial infections in all the cases we shared. And this sparked the initial idea that led me to explore this area of research in more depth in order to gain a better understanding of the situation.

Nav: Thank you, Guido. Thank you for sharing.

and Tuomas, this is your PhD now, right? This type of work.

Tuomas: [00:06:00] when I had decided that I wanted to specialize in infectious diseases and started looking for a research topic, I thought like probably everyone at that stage that I wanted to save the world.

And so I asked my future supervisor, Professor Anu Kantele, an if she was doing any research on, , malaria. And she said No, but, she was studying antimicrobial resistance in travelers. around that time, a lot of refugees were arriving from Afghanistan, Syria, and Iraq. and there was also political forces blaming migration for everything, like nowadays still unfortunately.

So the question became can we study this responsibly without adding to stigma, I guess that combination, AMR one of the biggest global health threats and then the clinical side to it. the migrant health, global health one health and the ethical questions around it all.

I'm [00:07:00] definitely not saving the world, but hopefully adding a, a small piece to this AMR puzzle

Nav: Thank you all for sharing and now we'll get to the topic of the day, which is antimicrobial resistance or AMR in conflict in crisis zones.

I think it's quite hard for any of us here and any of us listening to really ignore the numerous recent ongoing humanitarian crises and conflicts around the world. there's the Russian invasion and war in Ukraine with millions of Ukrainians displaced and the ongoing destruction warfare. This is the largest human displacement crisis in Europe since World War ii, the October 7th attack by Hamas resulting in the mass killing of Israeli civilians and hostages, and what followed, which is the genocide against Palestinians and Gaza by the Israeli government and the famine and the destruction of their healthcare system.

and what I feel like has been getting sort of the least attention, but it's probably the largest humanitarian crisis, is a civil war and genocide and famine in Sudan. I'd like to ask you all in this backdrop of war and genocide and famine and mass [00:08:00] displacement and just utter human devastation that's happening around the world, where does antimicrobial resistance fit in?

How do you tell our listeners? How do you tell, the global citizen why this is important to understand and why this is important to address?

Aula: thank you Nav. I think the first and most important thing is actually AMR is directly relevant to patients, and clinical responses in many of these settings. we have really had to work very hard in certain instances, and I'll give the example of Syria to make sure humanitarian organizations, both local and international, know the importance of AMR and that we must invest, in prevention foremost, but also in our ability to diagnose resistant bacteria.

to be able to respond effectively and also to make sure that we are putting in all the different aspects around infection prevention and control and antimicrobial stewardship with a very strong message. You can perform the most extensive, most advanced trauma surgery, or other [00:09:00] intervention.

But once wounds, are colonized or, infected with multi-drug resistant bacteria, your patients are going to have a very poor outcome . I'll draw on here a piece of work that Ahmet Aldbis did. So he's a remarkable man. . He's a pharmacist from Syria,

and he's worked in Ukraine, and in other, high intensity conflict settings. He did a piece on, conflict and antimicrobial resistance. This is one of the few qualitative pieces of research where we interviewed patients in Syria, and this is in the northwest.

So very challenging setting, who were affected by drug resistant bacteria. and of course they were also affected by, disabilities, different wounds, chronic wounds, injuries, But hearing from the voices of patients what it feels like to be living in a tented settlement and not being able to keep your wounds clean or re currently going in to have antibiotics, the expensive antibiotics, not being able to have your wounds healed, and therefore, having longer term disability, having an impact on your family, feeling [00:10:00] neglected as a result of all of this from a patient's perspective becomes very, very important.

I think. Secondly, in a conflict setting, we need to understand that it's an amplifier of all the different facts that can lead to AMR That would probably happen naturally. But in conflict, it happens in a very concentrated way. So the direct impacts that we see, are wounds not healing. in severe malnutrition, we see increased susceptibility to infection and therefore wounds not healing in addition.

So there are multiple factors in this setting where we need to give our patients the best chance to have a meaningful recovery. alongside this, what interests me in terms of AMR. Is seeing it through the lens of quality. So antimicrobial stewardship and infection prevention and control in particular are important .

Quality indicators in a programmatic and humanitarian response and remembering, yes, you can have very acute conflicts. And in some of the situations we've seen in Syria where we've had to have cave hospitals to underground hospitals because our [00:11:00] hospitals were being targeted by the former Syrian regime and by Russia, we had to drive hospitals underground.

Sadly, they were still targeted. In a setting like this the space for adequate cleaning and surgery of wounds, making sure that you've got the right prophylaxis in a setting where. you don't have the same ability to organize as you would in a proper healthcare facility becomes even more important.

Aula: And then lastly, AMR is fundamentally important in terms of the impact of conflict on the behaviors of both patients and the healthcare workers how they take antibiotics, how antibiotics are prescribed. So for me, this goes very much hand in hand. And of course, in an immediate conflict setting, you are thinking about the immediate conflict, but also, and hopefully , all conflicts will end.

what you will have after that, if you're not careful in the acute phases of the conflict, the most intense parts of the conflict, is the lasting legacy

Aula: of antimicrobial resistance.

I would love to hear from others as to how you think about this. Tomas, how do you [00:12:00] think about, the importance of AMR in such a challenging setting of just the humanitarian crisis at baseline that you deal with?

Tuomas: Yeah, I think Aula raised, very important points and I also. Believe strongly that we cannot think of AMR in isolation or as something separate. it goes through all healthcare and all, health. So, it's just like Aula said that if we close our eyes from this, then end result won't be, good.

and I also think that there are two layers here. First what happens locally, in the conflict area and, in the hospitals there. then secondly how that connects, globally and how, Armed conflicts, destroy hospitals and disrupt antimicrobial stewardship and infection prevention and control.

conflicts, force people into overcrowded camps with poor sanitation. And, we've studied refugees and asylum seekers that have traveled a long way, the living conditions on that transit, it also increases the risk for, [00:13:00] the MDR bacteria carriage. And, it works as an amplifier like Aula said.

Guido: yes. This is a key question I know in recent years, there has been an increase in armed conflicts around the world, including in Palestine, in Africa, with Sudan, the terrible crisis in Sudan and even in Europe.

And, honestly, I never expected this. of course it causes me sorrow, I often ask myself how I can respond to the threats and, what role I can play to avoid turning a blind eye to the problem. Honestly, initially I thought, I will simply continue with my, daily work, my routine work at the hospital, but then the discovery of multi-resistant bacteria in patients from refugee camps or war zones alarmed me.

Guido: later on I conducted a systematic review on wars and antibiotic resistance over the last 24, 25 years. I found out that scientific steward established on all armed conflicts documented, and not only high rates of [00:14:00] antimicrobial resistance, but also the presence of bacteria resistant to all the available antibiotics at the time.

And this was an eye opening discovery for me. I realize that global disorders and wars are probably among the main causes of antibiotic resistance, and that past conflicts still influence the lives of millions of people today. I believe that our work at the value of reminding us that All armed conflicts, whether far or near at some times a huge and difficult to predict repercussion that, uh, persists for a long time.

And the fact not only those directly involved, but also all of us globally, we all should remember this and act in our way to safeguard the effectiveness of antibiotics, to ensure a better quality of life for ourself, but also for future generations.

Nav: The way that you've explained this, I think is extremely helpful.

That it's an amplifier of locally what's already happening, the devastation is amplified even more. [00:15:00] And things you think you could repair potentially with surgery and trauma surgery, go the wrong direction when you have antimicrobial resistance that you're dealing with. then it also acts as an epicenter for global spread, right?

And so the bad breeds there in terms of antimicrobial resistance has the ability to spread globally as well. Thank you all for, sharing.

Tuomas: just to add I think it's crucial to remember that, AMR makes even common infections harder to treat and increases mortality and morbidity and, pushes already fragile health systems into collapse.

So, it's a global, thing, even though we are looking at specific conflicts.

Thomas: Thanks everyone. What would you say is generally the baseline AMR epidemiology or burden of disease in the crisis affected areas? In your experience, do you find that it's generally a high community prevalence of MDR bacteria before the crisis?

Or is this something that's emerging during this situation? Like you have a low prevalence, but it can [00:16:00] increase to a high resistance setting? What do you think?

Aula: I think this is a really important question.

We don't have great data. We've done a recent systematic review, where we've only identified around 29 studies of very variable quality over the last 10 years. The suggestion is there was probably already a lot of drug resistance, but it's increased as a result of the conflict. One thing, and it's not scientific, but I would say from around 20 16, 20 17 is really when people started to talk about AMR in the context of Syria. and that became more amplified from the local healthcare workers in particular highlighting it. What's interesting about Yemen is when the conflict was ongoing there, it was quite relatively early in their conflict that the healthcare workers started to say, well, actually, we're seeing an awful lot of what we presume are drug resistant bacteria.

let's go to Gaza. So from the work of my colleagues in Medicines sans Frontier, they published data that suggested that high rates of [00:17:00] gram-negative resistance in particular, were evident even before this latest conflict from October, 2023. we have some data since then. Again, a variable quality, which shows very alarming rates of drug resistance.

So stepping back in my area of expertise is more probably the EMRO region, the WHO Eastern Mediterranean Regional Office. and I would say in this particular region, we know that rates of, MDROs so multi-drug resistant organisms are high in this particular region. And for those countries affected by conflict, they're probably even higher.

Aula: and probably like we said, amplified and probably exaggerated by the impact of the conflict with all the associated stresses on the health system. some of the other countries under huge stresses of conflict, we've mentioned Sudan, but also we have to remember South Sudan, the DRC, CAR, Chad, Northern Nigerian, and sadly many other countries. .

We may not necessarily have robust data that will allow us to answer some of these questions .

in most, conflict [00:18:00] areas, the AMR prevalence is already high before the fighting starts. And then the conflict just is like throwing gasoline Into fire. And because they're like in many low and middle income countries, you already have poverty and weak healthcare systems and poor water sanitation and hygiene and maybe unregulated antibiotic use and limited diagnostics or stewardship programs already.

but not, all conflicts are the same, of course, from our research also, in Ukraine, the biggest burden of AMR seems to be in the hospitals. But, over time it will spill over to the community and globally as well.

Guido: I agree with Aula, and Tuomas. And, I also believe that, every armed conflict is unique in some way. Different conflicts involve different areas of the world, people with different cultures and customs, different geographical regions and climates and different levels of economic and natural resources.

And they also involve different weapons [00:19:00] used by the enemy factions, and also different levels of support and assistance from other nations based on the availability and the attention given in public debate. so it's difficult to generalize. and also many armed conflicts last for several years, and often are, preceded by other conflicts within relatively short period of time.

So this introduces, bias and makes it difficult to determine whether an armed conflict. Simply catalyze antibiotic resistance or is the direct cause of AMR antibiotic resistance? we know that, numerous published studies tested an high rate of AMR even before the current conflicts in Ukraine or in Gaza.

However, based on the available literature, it's clear that the current conflicts have significantly increased the prevalence of multi-drug resistance material and also they contributed to their global [00:20:00] spread. And in the case of Ukraine, even new resistance mechanisms have been, described. So for this reason, I believe, we can conclude that war is the main cause of the phenomenon and not merely the catalyst of, Antibiotic resistance.

Tuomas: Yeah. We just published, our article war on Antimicrobial Resistance, high carriage rates of multi drug resistant bacteria among War injured Ukrainian refugees in CMI. After Russia's full scale invasion. thousands of patients have been transferred from Ukraine to other European countries, we looked at 166 Ukrainian refugees treated in Helsinki University Hospital, and we grouped them whether they had been hospitalized abroad within 12 months, and especially whether it was due to war injuries.

And nearly half of those hospitalized for other reasons carried MDR bacteria and almost 80% of the war injury patients carried MDR bacteria and also the war injury [00:21:00] patients carried the most resistant, difficult to treat strains such as Carbapenemase producing Klebsiella, Acinetobacter baumannii, pseudomonas, unfortunately, nearly half of the war injured

MDR carriers also developed clinical MDR infections mainly complicated wound infections of osteomyelitis and foreign body infections. And naturally we recommend targeted MDR screening and strict conduct precautions for these patients. Of the non hospitalized refugees, only 18% carried MDR bacteria and mostly ESBL and just a few MRSAs.

No CPE or, resistant acinetobacter, pseudomonas were found. So in our research, it seems that the problem relates specifically to hospital setting and, the prevalence of antimicrobial resistance among the ordinary refugees from Ukraine is, no more common than, for example, [00:22:00] Finns who travel to Asia.

Nav: And I wanna stay on that point just a bit. is it about these spaces, these conflict zones, these crisis zones that allows antimicrobial resistance to thrive? what is it that's driving the emergence and the spread of resistance in these settings and even beyond these settings?

And you mentioned a little bit, but I wanted to stay on that as well as hear from, all of you

in this, it's a complex, phenomenon from the hospital setting, I think it's the destruction of hospitals and the disruption of infection prevention and control and antimicrobial stewardship. And I guess the chaos in general leads to unregulated inappropriate antimicrobial use, as well as lapses in, antimicrobial stewardship and diagnostics. outside the hospital, the overcrowding, in refugee camps. And, then the whole infrastructure, like poor access to water and sanitation and hygiene, increase the risk, and also, of course, the barriers [00:23:00] to, reach healthcare.

Guido: Yeah. Yeah. Tuomas agree with you. I think, from an evidence-based point of view, we don't have such a strong evidence of the exact causes of antimicrobial resistance during war. We know that, wars, caused the development of antimicrobial resistance, but we don't know the exact causes.

There are several hypothesis. first of all, the damage to laboratory facilities in war zones. , Including antimicrobial susceptability testing. So this kind of testing is crucial for ensuring the appropriate use of antibiotics. Second, I think the incidence of traumatic injuries, like, Aula was, saying earlier.

injured people and refugees often, needs damage controlled surgery. this procedures are often performed in, uh, facilities lacking adequate infection controlled measures. So the risk of tissue contamination, can lead to an increase incidence of, [00:24:00] Complications, and. promoting the development of antimicrobial resistance. I also think paradoxically, healthcare workers in order to address these issues frequently employ broad spectrum antibiotics, which can contribute to the emergence of, resistant strains. from the studies, performed in Iraq, we know the high incidence of, MDR Acinetobacter baumannii, can be linked to the presence of integrons, integrons that can carry antimicrobial resistant genes.

so in the, military hospital, the overcrowding of, patients and soldiers and, carriers of, multi-drug resistance bacteria facilitates the genetic transmissions of these, resistant genes. in addition for sure, the inadequate disinfection procedures and content transmissions are, playing a significant role in the spread of, uh, multi-drug resistance material.

finally, from my experience, surveillance studies [00:25:00] adopting molecular and genetic characterization, provide data supporting the nosocomial transmission of multi-drug resistance bacteria. So probably transmission within military hospitals and healthcare facilities plays, a key role.

Aula: and just to add to that,

I don't think we can say one thing leads to drug resistance, it's multiple, if we zoom out and think about many of these conflict settings.

Aula: Increasingly, we are seeing the overlap with climate change and all the impacts that climate change will have in terms of, drought or even flooding. And we know that is also associated with antimicrobial resistance, but also the damage to environment and therefore the contamination of local water sources, which, if you don't have adequate water and water infrastructure or like in the case of Syria, Gaza and elsewhere, water is deliberately damaged alongside healthcare.

as part of the, activities of the conflict, you'll find that you might get more contamination. Then the other bit that's very interesting for me, and actually what my [00:26:00] research will be more about is some of the more social science aspects, the qualitative aspects, these sort of softer or behavioral aspects , whether it's patients, whether it's healthcare workers, whether it's the communities, how they interact in this particular ecosystem.

and here I'm gonna quote Omar Dewachi because, listening to him is always insightful. So he's a surgeon by background from Iraq, did a lot of excellent work on Acinetobacter in Iraq and he said something to me about, well, what do antibiotics mean to patients in conflict settings?

What do they mean to refugees? What is the agency of, of an antibiotic for a patient? And so for all of us, if we. found ourself in a situation where we are desperate. If we had antibiotics, we may try and take them, if we think that we need them, , even if it's minor, even if it's without, healthcare guidance, which is often the case in these systems.

And then of course, remember when you see vulnerable refugees without agency traveling, and let's say traveling from parts of the Africa [00:27:00] region or the EMRO region, across Turkey, into Greece, into Northern Europe. We know for a whole variety of reasons, these health systems are not refugee or migrant sensitive.

And what that means is affected refugees who may have infections, probably don't want to access these health systems for a variety of reasons. And if they do, there may be barriers that prevent them from adequately, being able to understand and receive the care they need. So in that instance, and WHO Euro has done some really important work around this.

They may hold antibiotics and keep them and then take them even without guidance or share them out, with family members, let's say if they're injured during their journey. So I think some of these sorts of behaviors are also really important to understand, because they put in some specific selective pressures that we probably don't see, in some of the other settings, affected by, antimicrobial resistance.

Tuomas: I really liked that you brought up climate change, which I see as a similar kind of very complex, problem as [00:28:00] AMR luckily many of the things that we would do trying to stop climate change are the same as that we would do to try to, tackle the AMR problems.

So I think in a way that's good, but of course we have to do, those actions.

Thomas: So you mentioned some of this already, but, I wanted to ask you about the role of antimicrobial stewardship in conflict zones and also diagnostic stewardship. Is there even an ability to think about these things in this situation?

Like if you have limited resources or limited access to drugs, how can you work with this in the outpatient setting or settings where you don't have access to prescribers or diagnostics? How can you work with this in hospitals which is a very different situation?

Guido: I wanna say diagnostic and, antimicrobial stewardship, go together and, are essential because they prevent patients from receiving indiscriminate long term antibiotic treatment with broad spectrum antibiotics. And, uh, so [00:29:00] enabling the rational use of antibiotic therapies and targeted treatments is fundamental to limiting the onset of antimicrobial resistance.

I think, antimicrobial stewardship is feasible even in, conflict zones and during wars, my approach is to consider antimicrobial stewardship as the, rational use of antimicrobials. Of course, we need, uh. Data. And I think we need the networking with the colleagues and the healthcare workers, spending, practicing every day in that zones to understand, what they, the store, which kind of antibiotics they use and, are available at the time, which kind of diagnostic and, which kind of tests they can apply, but we can, target and design the best, antimicrobial stewardship, programs for them.

And I think it's one of the key approach

to reduce the problem.

Yeah, I also

Tuomas: understand that it's, very hard to talk about stewardship [00:30:00] when people are treating patients under fire. but I, think it should be, supported by the global medical community with education and international collaboration. And like I said, it's hard to tell somebody in, those zones what to do. from Finland

But I still believe that stewardship is not like a luxury thing that we can do, uh, when we have everything else sorted out. And even in these settings, I, think it's the thing that keeps our antibiotics still working.

Aula: I just want to add to that, remember when we're talking about conflict zones, it's not a monolith. You can have an acute conflict.

chronic conflict. You can have a country where one part of it's in conflict. So remember

Aula: what's happening in Gaza is horrific, but not all parts of the country are in the same levels of conflict across,

all times. In Syria.

at the moment, arguably we probably have conflict in southern areas. in the last few months we've had conflict in, coastal areas, but over the years of the conflict it was mostly outside of areas under former regime [00:31:00] control. So predominantly the northwest where we saw the biggest attacks, the biggest impacts on the healthcare systems.

So there's lots of different types of conflict and also different stages. I think what you are getting at is in that very acute immediate injury where there is chaos and a flood, of traumatic injuries. And in that chaos, what is the role of antimicrobial stewardship? I can say we can do our best to advise, but perhaps there's very little that we can do.

So we know from our patients that we interviewed with Ahmet Aldbis's work. They probably didn't know antibiotics they were given, they were probably given whatever was to hand, because of course, in these situations, there's a breakdown of supply. You get what you're given. Remember, we as, I presume predominantly ID physicians, must also work very closely with our surgical colleagues because they are probably among the most important of the immediate time of an injury in terms of what they do and the decisions they make, the debridement, the washout, and then that sort of treat and transfer approach.

So when you've transferred a patient to somewhere that we hope [00:32:00] is relatively less acute in terms of conflict and when you start getting these chronic wounds, chronic infections. That really is the time where careful antimicrobial stewardship, and careful tailoring if you're lucky enough to have microbiology in that setting to what you're finding in these particular wounds, but also making the right decisions.

Just because you've identified a bacteria that's very resistant. Let's give an example of acinetobacter. Does that mean that's the causative organism for the infection at that particular time? It may well be, but we all know that acinetobacter is also quite indolent, so it may not be the causative, organism at that time.

Aula: secondly, there are other decisions that can be made, . So when we talk about stewardship, we also need to make the right decisions around the durations of antibiotics. So you treating a superficial infection and therefore only giving a relatively short course, or do you think it's a deeper infection and therefore needs a longer course and related to stewardship?

in terms of [00:33:00] access to diagnostics, in most instances it would be good if you were treating osteomyelitis. If you were able to get samples of bone to be able to send them, because otherwise we are committing patients to a lot of antibiotics, a lot of complications, and maybe increasing risks of resistance.

And sadly, I know that to be the case, in the very acute settings, in Northwest Syria. And actually the cohort that Ahmet had interviewed, some of them were antibiotics for months. So we owe that to our patients, in that particular situation. And then lastly, something that's important that we globally in the infection community are discussing is IV to oral switches and the bioavailability of certain antibiotics.

Aula: and we know that we may be perhaps giving longer intravenously than we should be, and we're seeing a shift change, but that becomes imperative in an area of conflict. The last few years have shown us hospitals and healthcare facilities are not safe for patients.

So you cannot have patient. In hospital needing intravenous antibiotics. the patients in [00:34:00] Syria repeatedly said to us they want to go home. they prefer to be offsite because they know they're at greater risk in the hospital. And then if we step back, what is it that we as a global infection community need to do?

We need to advocate, we need to support better perhaps point of care diagnostics or simpler diagnostics in some of these incredibly austere settings. We need to advocate and support, protocols in terms of what antibiotics can be used in different situations. And then we also need to link in better with our local colleagues.

There may well be microbiologists, but for microbiologists they may really struggle if they don't have access to laboratories in Gaza most of the laboratories have been destroyed, with major attacks on most of the healthcare facilities. We also have major shortages of infection specialists So in Syria. The numbers are probably around 20 for the whole country, and they're centered in Damascus and Latakia. So having people that you can pick up the phone to and say, this is the [00:35:00] situation, this is what's happened, what is the right approach in terms of the infection side of the management, therefore becomes really important.

Aula: And I think that's where we as a global infection community can support our colleagues in these really austere environments.

Nav: I wanna stay with you here because that brings me to the next point about infection prevention, especially across the heterogeneity that you see in a country with conflict in certain regions and how that might differ across the settings, whether it's hospitals, outpatient settings.

What have you seen as the capacity to implement routine infection prevention practices, across the healthcare infrastructure?

Aula: So in terms of infection prevention, it can be incredibly difficult. We just need to look at what's happened in Gaza I've said that many of the hospitals have been, sadly attacked, and many of them out of function. But remember what we're also seeing, is people in the community seeking shelter. In hospitals or health facilities thinking they may be safer. and of course that's very tragic because we know that not to be the case in many of these [00:36:00] settings, but also from a microbiology perspective, this becomes interesting for the most part, we sometimes think of slightly more community patterns of drug resistant bacteria compared to hospital associated or, hospital acquired infections. And we're seeing blurring of the lines, in some of these conflict settings. We've seen the same in Syria, in Ukraine, in Sudan as well, with people trying to seek shelter in these health facilities.

and sadly with Ill effect, with IPC, the simple measures or contextual measures are probably the most important here. So we know, for example, handwashing best as we can in these settings, making sure you've got antiseptics. And again, that becomes really important because we are seeing vast interruptions of humanitarian aid.

And that also includes antiseptics as we have seen in Gaza. There is another challenge that we have seen in Syria, and I'm sure it's evident elsewhere. So in areas that were outside of regime control, we started seeing lots of so-called field hospitals.

And I've mentioned the cave hospitals as well. So field hospitals can be a number of [00:37:00] things. It can be an old restaurant or a hotel, or an old building and it's converted into some sort of health facility. So you can imagine how inadequate this is in terms of the delivery of healthcare, but also in the delivery of infection prevention and control.

And the other thing that we haven't discussed quite yet, about conflict and infection control is the additional challenges of whether it's a natural disaster in Syria. We saw the impacts of the earthquakes, which also affected Southeastern Turkey, but also the impacts of pandemics.

So in Syria, as in other countries we were affected by COVID-19. Then it becomes very complicated because I was being asked about isolation procedures for COVID 19 in some of these so-called field hospitals where they didn't have side rooms, they didn't have appropriate areas for donning and doffing.

There wasn't appropriate waste management. and it was very difficult to come up with any sort of appropriate protocol that can be implemented in these settings. We've got some brilliant IPC specialists, in Syria, and also some of my colleagues in MSF who specialize in this.

and they come up with creative [00:38:00] ideas that are appropriate to a particular local context. and I think, we need to follow their lead and their advice, knowing the challenges that we face, and also in close collaboration, with the local healthcare workers, to understand what is or isn't practicable in a particular situation.

Guido: I totally agree with, Aula. I think, supporting colleagues and, doctors and healthcare personnel in those hospitals. Hospitals in the conflict zones is crucial. But I think, it's also really important that we as a international scientific community and, international society should step in and, think about this issue.

And highlight these critical issues even in guidelines. For example, I can remember I recently revised, around seven international guidelines on the, treatment of, deep seeded infections and soft tissues, infections, and, only two out seven guidelines had specific paragraphs [00:39:00] on, the treatment of contaminated wounds and complex wound due to, crushing fractures or, wounds.

no guidelines had specific paragraph on the treatment of disinfection in the setting of crisis zones or refugees, or even war zones. So, I think also, this should be, highlighted and, that's important because, we also have some evidence, not so many studies, but the few available studies show that, potent in practice, antimicrobial stewardship and infection control procedures is effective even in military hospitals.

Guido: a group of colleagues working at the, Brook Army Medical Centers from the US during the Iraqi conflicts. They demonstrated that infection control procedures over three years, time, were effective in reducing the rate of, multi-drug resistant Acinetobacter baumannii.

Of course, this study was conducted in a hospital with [00:40:00] adequate resources, but, I think one possibility, will be to establish a network of doctors healthcare personnel, and then through surveys and questionnaires, assess, understand, their specific capabilities, how they are controlling infection, and offer proper support.

Thomas: And speaking about that, What challenges are there when it comes to surveillance and monitoring of these events and, in the evaluation of interventions

that we discussed before? And how would you begin to assess the scale of AMR in conflict zones or humanitarian tearing crisis?

in, these situations the whole scale destruction of many of the laboratory infrastructure, is that we just don't have sufficient information. And where we do it's often, if not the right quality. So, that can become highly problematic and also quite misleading.

Aula: of course, conflict affects, the practices of healthcare workers and when they do or don't send, samples, even if there is a local laboratory for a number of reasons. The patients [00:41:00] may not be able to afford it, even if the patient can afford it, or if the, microbiology laboratory is, free at the point of access, they may have very little faith in the results.

So we often get told, well, we keep sending, samples, they always come back as negative. Or, they come up with unusual results and therefore it doesn't help the clinician, or they take too long I'll draw on the work of Reem Abu-Shomar. She's a remarkable microbiologist, from Gaza . So part of this work was to take samples from, different water facilities in different health facilities in Gaza to understand the degree of contamination there, because of course, if you find you've got high rates of drug resistant organisms, it might lead to.

Contamination whether through, staff members spreading or whether through the practices around water and sanitation. And therefore hospital acquired infections, for patients who are already vulnerable in hospital. And what she showed from that particular piece of work, and she's building on this, is very high rates of multi-drug resistance, pseudomonas And we know how much of a [00:42:00] problem that is in healthcare facilities and in nosocomial infections. the one message I do have here is it's imperative for us to have some sort of surveillance system, in place, even if it's basic. I'll draw on the work of Antoine Abou Fayad, who's at the American University of Beirut. He's done remarkable work building links even in the most complicated crises. Yemen, Syria, Lebanon, and even Gaza and elsewhere. And almost keeping a biobank of these samples because even if they're not being, processed in real time Knowing what bacteria are there, what bacteria are developing. And there's been some good work over years, particularly with Acinetobacter, to understand the resistance mechanisms, and how they have evolved over time. going back to what we said before, when we think of conflict, we think of the most acute crisis.

But actually there are many, low level conflicts or protracted conflicts where there may be operating space, , with the right, collaboration, the right ability to access and the [00:43:00] right intention to support our patients and local healthcare workers, in these situations.

Nav: we've painted a pretty strong picture of many of the challenges in the variety of conflict zones and crisis zones throughout the world, . But what are some of the successes that you all can share in trying to combat antico resistance in these humanitarian crises?

are there any innovative approaches? To improve the management in these crises, whether it's structural from how systems work, as well as at the patient level, .

Guido: Yes. I think from my side, the, most relevant, the greatest, achievement that, we obtained was to draw the attention of the scientific community and hopefully also public opinion today. Show of antibiotic resistance in armed conflicts. I hope, I'm quite confident that this will help to contain the problem in the near future and, the involvement of large scientific society also.

For example, the [00:44:00] European Union of Medical Specialties. In establishing a network of colleagues and a network to support doctors and care workers in the frontline to control, antimicrobial resistance, infection was a, a huge, a huge achievement, regarding the, future approaches. I think, the adoption of whole genome sequencing will be, of help identifying the exact mechanisms of antibiotic resistance and to clarify what's

going on.

Aula: just to add to that, there have been some remarkable innovations in this particular field and sort of conflict in humanitarian crises. I would argue that Medicine Sans Frontier has been at the forefront, with a number of interventions, one of which is the AI app antibiogo, which is there to support sort of laboratory, colleagues.

And they've successfully implemented it, particularly in Yemen. One of the forgotten conflicts and crises that we, don't speak about. And they have significant, issues relating to infection prevention and control stewardship, and also drug resistant bacteria. [00:45:00] and you may have heard of the mini lab project, which MSF has launched after many years of hard work bringing together different experts.

The idea behind the mini lab project is, in a few large containers. They can deploy this in an austere environment. And within 24, 48 hours they can assemble it. It's got a, cabinet. it's got blood cultures. you can train local staff, even if they're not microbiologists, to develop the skills that they need to be able to do a basic set, of microbiology tests.

and it's self-contained in terms of all the other important things around waste management and, things like that as well. the other important innovation I've drawn in terms of laboratory diagnostics as what some of my remarkable Syrian colleagues have done.

So a few years ago, Nabil Karah

what he

did was have quite a basic microscope, a basic camera, so like an iPhone or something like that, a porter cabin. And then he trained up the microbiology laboratory technicians, to be [00:46:00] able to process the samples in close collaboration, share their findings on a secure system, and get feedback either from him or other microbiology colleagues in terms of interpreting for AST what the right recommendations are in terms of sort of antibiotics.

So these are some of the broader innovations that can be done. For me. I don't think we need to look for the big innovations. I really think simple is best, low cost is best, and therefore, what we must do as an international community is probably two things. One, we have a duty to link in and support our local colleagues, whether it's through education, mentorship, real-time support.

one of the things my Syrian colleagues, did, recently, is we have different sorts of WhatsApp groups, and ways for them to communicate in real time about patients that they're concerned with. the other thing, that has been useful , I've learned a tremendous amount from my colleagues who are not infection specialists.

Aula: So. a trauma surgeon, what is your approach to wound management and [00:47:00] immediate surgery and how you think about, prosthetic materials you're introducing and debridement? we must be very broad and inclusive in our discussions on AMR. And I think we are mostly infection specialists here. I've learned a tremendous amount also from anthropologists and behavioral science specialists in terms of understanding how to define and tackle the contextual issues in a particular environment, but also policy makers, also economists.

I've had to speak to international organizations like the WHO, the un, to highlight this issue because actually two things, they often hold funding and they can offer influence if they feel strongly about a particular topic.

Aula: And some of them have felt very strongly about AMR because of all the implications that it has. And so I think for us to be imaginative and inclusive more broadly, but also to speak very clearly. Thomas and Nav, you've asked about. What innovations have happened and what are the solutions?

But I really want us to step back [00:48:00] because I don't think we should have a conversation around conflict in AMR without stating very clearly. conflicts must stop and the harming of healthcare and of civilians must stop because otherwise we're only ever dealing with the aftermath, of conflict and the impact on civilians, often long term.

So if you think about Gaza, more than 30,000 children have been killed and thousands more have been injured, and that's going to take a very long time to heal. With the additional challenge, of being a child that's growing.

and we know even with the best circumstances with physiotherapy, occupational therapy, those that can support with prosthesis, this is going to be a long and difficult journey for these children.

So I think we as an infection community, need to one, be able to speak to the wider community, but also try and use our influence to be able to say, actually conflict must not happen and children must not be affected and civilians must not be affected given the huge toll, on these populations.

Nav: I couldn't agree with you more. I [00:49:00] think making sure to

recognize, the geopolitical influence of how these conflicts, Evolve and what the impact is in terms of some of the points that you made, even of not being able to receive supplies, but also antiseptics and other things that keep healthcare systems going and how that impact trickles down and to further long-term sort of devastation in these settings.

I think, you can't overemphasize how important those connections are from on the ground bedside decisions that are being made all the way to the scale of policy and global policy and international law or violation of international law in these instances. Thank you Aula, for those comments. .

Thomas: So, we've discussed a lot today.

ranging from contaminations or possible role of environment and all the way to policy level. but if you would have to choose what do you think is the most urgent priority to best prevent unlimited spread and consequences of AMR in crisis would you go for infection control, antimicrobial [00:50:00] stewardship?

would you go for the field hospitals or later stages, hospitals or ICUs? Where do you think we can make the most impact?

Guido: I believe that, in order to contain the phenomenon of, uh, antimicrobial resistance in war zones, the priority should be to provide a great, training and support for the staff and, uh, doctors working in, uh, military hospitals and, in healthcare, uh, structure closest to the conflict.

we should help them to, extract, provide data and information on the current state of the resources, the microbiological tests available to them, the antibiotics they have at their disposal in order to design and, and then to implement infection control and stewardship protocols. Tailored to them, to their specific needs.

in that particular context, I think this should be the priority, besides of course raise, the international, awareness and attention

[00:51:00] to this issue.

Aula: I'm sometimes asked, what would you prefer this or this? But for me, I tend to think of things being multimodal parallel and trying to move forward with a little bit of each of these at any given time. And I don't think it would surprise you for me to say actually.

We need political will. We need funding. We need engaged policy makers. We need high level influential people to really take this on and really understand. The words of of the local healthcare workers around how important AMR is to their clinical practice in conflict settings.

In some settings, we still have to make a case that there is an association between AMR and conflict that's different from let's say AMR and other low resource settings where health systems, are affected a number of different ways. And I think partly the reason for that is, there are some similarities, but of course there are also clear differences.

And very importantly, perhaps we as an [00:52:00] infection community or we involved in this space are maybe not reaching all the levels we need to, or maybe given the complexity and range of this topic not being clear enough in our messaging around this particular issue and the drivers of AMR in conflict settings.

So I really do think we need more research, really defining the problem in real practical ways. We need operational and implementation research that goes beyond the theoretical to really understand how we make an impact in all these very different contexts. 'cause what works in Gaza won't work in Ukraine.

What works in Ukraine will be different than what's needed in Yemen, in Sudan, because these are all very, very different contexts. and then I think the last thing, and it echoes a little bit to what Guido said, for a long time we've wanted training courses that are multidisciplinary, that are aimed at healthcare workers that come from the different disciplines that come from, Those of us involved in the infection and [00:53:00] microbiology space, surgeons, pharmacists and how to approach antimicrobial stewardship in these particular settings. Because ultimately in many of these conflict affected settings, they need support and they're often not specialists, they're usually. generalists, often more junior, because we know that conflict has a major impact on education and training. and we know that healthcare workers are also being killed.

And I think that's something also important for us to recognize, in this sort of space. So they're losing some of their senior mentors, in this particular situation. So these are some of the things that we can try and advocate for, because what we need to do is the theoretical, the technical, but also the very direct and the very practical, as we try and, tackle this very important and very real problem.

Thomas: Obviously I didn't want to choose one thing, but it's a very complex challenge and we need to work on all parts of the problem, possible solution.

I think it's worth hearing though, especially when you talk about global challenges, everybody thinks about, oh, what should you prioritize, right? If you had [00:54:00] to pick within silos, Supplies? Is it personnel?

Nav: Is it systems? Is it, infection prevention practices? I think it's certainly worth hearing, and Aula you articulated very well that you need integrated approaches because, there's, many layers to the complexity of, antimicrobial resistance, many challenges both internally within the conflict and how it spreads even wider.

And so it's worth. Hopefully for many of our listeners to understand that these , multidisciplinary approaches, extremely important from the technical of the surgical aspects, all the way to the anthropology and behavioral aspects. and then at the top is the political will to actually, work on the underlying problem, which is the conflict and crisis to begin with.

So thank you very much, all of you. it's really been a fascinating discussion. I'm really grateful for the opportunity to, meet and discuss this with you. before we wrap up, we've talked about a lot of messages, but I just wanted to give one last opportunity to each of you if you have any final words for our listeners,

Guido: [00:55:00] I think, the biggest challenge when dealing with patient and, casualties from war zones is the profound emotional impact that this entails. And, the orders of war are painful for our sensibilities, for our souls. But I think we should not, we must not allow ourself to be overwhelmed by brutality, by injustice.

I believe each of us can make a difference, and even simply doing our daily duty, but without turning a blind eye to wars and injustice, by joining force, we can achieve great results. I believe in scientific research and evidence-based medicine. they are powerful tools that, will allow us to understand what's happening in the world, to defend ourself against, warfare, for example.

and also to control the side effects of war including antimicrobial resistance. as infectious disease physicians. I believe, that's really, [00:56:00] truly worth fighting this battle in order to. ensure effective antibiotics for, ourself and our future generations all around the world.

Tuomas: Yeah.

Reflecting on my own research among these vulnerable populations, we need equal access to care, including refugees, asylum seekers, and undocumented migrants. It's the ethical thing to do, but it's also just smart policy delayed treatment always costs more and makes infections and all diseases harder to treat.

modern medicine stands on the shoulders of antibiotics that work and fighting AMR is already hard enough without war and conflict. And I have huge respect for all the healthcare workers who risk their lives trying to save lives and make difference in those conditions.

Nav: thank you so much again to our guests. Aula Abarra in London, England, Guido Granata in Rome, Italy, and Tuomas Aro in Helsinki, [00:57:00] Finland.

Thank you for listening to communicable the CMI Comms podcast. This episode was hosted by me Navaneeth Narayanan in New Jersey in the United States, and Thomas Tangden in Uppsala Sweden, editors at CMI Comms ESCMID's Open Access Journal. It was edited and produced by Dr. Katie Hostetler-Oi and peer reviewed by Dr.

Ariana Zerja of the Mother Teresa University Hospital Center. Tirana Albania theme music was composed and conducted by Joseph McDade. This episode will be citable with the written summary referenced by A DOI in the next eight weeks. And any literature we've discussed today can be found in the show notes. You can subscribe to Communicable wherever you get your podcasts, or you can find it on ESCMID's website for CMI Comms Thank you for listening and helping CMI, comms and ESCMID move the conversation in ID and clinical microbiology further along.

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