Hospital plumbing as a reservoir for resistance – an interview with Amy Mathers

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In line with our October focus on healthcare-associated infections, we spoke to Amy Mathers about her research on the role of hospital plumbing in the evolution and exchange of genes of drug resistance.

Amy discussed her research on sink traps, toilets and wastewater, what solutions hospitals can use and antibiotic resistance in the broader context – including the role of infection prevention and control.

Listen to the podcast, or read the interview in full below.

00:42 – Amy’s presentation at ASM Microbe

02:37 – Implications for hospitals and patients

05:08 – The importance of basic infection control

06:28 – The wastewater plumbing environment and transmission of genes of drug resistance

08:43 – Strategies to tackle antibiotic resistance

10:24 – Stewardship and prevention

12:27 – Where might the field be in 5–10 years time?

Martha: Hi and welcome to Infectious Diseases Hub, I’m Martha, the Editor, and today I’m joined by Amy Mathers an Assistant Professor at the University of Virginia, School of Medicine (VA, USA).

Amy: So I’m Amy Mathers, I’m an infectious Disease Physician, my primary job is antibiotic stewardship – helping physicians prescribe antibiotics in the hospital – and I’m also Associate Director of the Clinical Microbiology Lab. My research is focused on emerging drug resistance, especially in Gram-negative bacteria, and how those organisms are evolving quite quickly through the sharing of DNA.

Martha: Amy spoke to me during ASM Microbe (7–11 June, GA, USA) in June, where she presented some of her research on the wastewater environment and drug resistance; here, she gives us a little bit of an overview of her presentation.

Amy: So, I will be presenting work on understanding how a gene of drug resistance that’s quite consequential has moved between bacterial species in our hospital system and how it’s involved with premise plumbing – not tap water or drinking water but wastewater, sink traps and toilets. And unfortunately, because organisms such as Gram-negatives can do quite well in the water environment, wastewater is a very good place for them to exchange drug resistance and evolve.

What we’ve found in our hospital; we couldn’t understand where patients were getting these drug-resistant bacteria from and ultimately through genomics and recognizing that the wastewater environment might be involved we identified that [this environment]was partially where our patients were getting drug-resistant pathogens – from back-splashing in the hospital and dispersion when you flush the toilet. So we deployed an intervention in our hospital to put lids on the toilet and we cut our acquisition rate for drug-resistant pathogens of this type in half – that’s part of what I’m going to be presenting on.

Martha: Amy went on to tell me a bit more about the topics she’s researching, including the building of a ‘sink lab’ – which, as it sounds is literally a lab full of sinks!

Amy: Some of the work that we’ve done in the lab – we’ve actually established a sink lab to really understand and model how bacteria are evolving in the wastewater environment; what’s important to propagating genes of drug resistance in the wastewater environment and how are they dispersing from the drain into a patient-care environment and really trying to model dispersion size, droplet size verses aerosol.

Martha: With interesting findings in the area of wastewater, Amy told us more about what implications her findings could have for hospitals and patients in the future, and what solutions could be provided to mitigate the transmission of resistance.

Amy: We’ve been trying to come up with really practical solutions to this problem because I think when I started with an understanding that our wastewater might be involved there were only about 35 publications, there’s now over 100 publications and as genes of drug resistance become more consequential I think people are going to be recognizing the premise plumbing as a source of drug resistance more and more.

It can send panic into any hospital administrator to find out that they’ve got lots of genes of drug resistance in their plumbing and they want to get rid of it immediately! But we’ve found through trial and error that just ripping it out doesn’t work; it basically comes back very quickly because the premise plumbing is all connected so that biofilm containing genes of drug resistance is still there and we’ve found that these organisms can move backwards in the plumbing at about an inch a day or quicker. It’s only a temporary fix, so the question is: what type of solutions can we provide to hospitals that will help mitigate or decrease transmission?

We’re also trying to understand how sink usage in the hospital can make the situation worse. For example, In our sink lab one thing that we’ve found is that nutrients are really critical to amplifying these types of bacteria that are of clinical consequence and so we really need to rethink how we’re using drains in the hospital – in the USA I think we’ve all become really accustomed to sinks also being garbage disposals for getting rid of unused beverages, liquid waste. Even IV fluids and some medicines all go down the sink drain and that might amplify the problem. We’ve recently published a study where we’ve done video surveillance of what was going down the drain in a hospital.

So I’m hoping to provide really practical solutions around sink usage to try to minimize this issue because I think our drains are going to be full of drug-resistant bacteria from here on out and I think a hospital is a place where that’s probably going to be amplified, so what can we do to minimize the risk to patients?

Martha: This research might lead people to focus solely on hospital plumbing as the issue, however,  Amy was keen to point out that basic infection control is absolutely still necessary.

Amy: The first thing I would say, and I always say, is that I don’t want my work to mean people shouldn’t wash their hands. Hand hygiene is still very critical in spreading drug-resistant pathogens from patient-to-patient so making sure that you’ve got really good basic infection control measures in your hospital to prevent spread from patient-to-patient is paramount and remains paramount.

I think that this [premise plumbing]is a portion of transmission of drug resistance but it is definitely not the whole and we know there are other risks in the hospital environment that can transmit drug-resistant pathogens or other pathogens that can live on surfaces e.g., if you don’t clean equipment between patients you can transmit organisms like this or things like Clostridium difficile or MRSA. So cleaning of hospital equipment and just  basic infection control remains really critical to this issue and I don’t want my science to overstate the issue of premise plumbing and its role in transmitting drug resistance but I also think we have to pay attention to it because it’s where a lot of evolution is occurring.

Martha: With regards to transmission of drug resistance in the wastewater plumbing environment, Amy explained why this is a key environment and why it presents such a big problem.

Amy: How is this helping genes of drug resistance evolve? That probably isn’t happening as frequently in dry environments as it does in a sink trap. Bacteria can create protein and DNA matrices that somewhat protect them and those build up in drains and it creates a perfect moist environment for bacteria to exchange genes of drug resistance – especially when they’re under different pressures. A lot of the genes that I follow are on mobile pieces of DNA that can be traded back and forth between bacteria and might have other genes on there like heavy metal resistance or other types of genes of drug resistance that may promote transmission because they all travel in a single DNA packet between bacteria. So it is an ideal environment for the evolution of drug resistance unfortunately and I think that is the bigger issue in the long term – how is the hospital wastewater environment amplifying the problem?

The other issue is that patients with these types of bacteria end up in hospitals – it’s the first place that drug-resistant pathogens go – so then the worst-of-the-worst genes end up in the hospital, then end up in the sink and end up in the wastewater. On top of this we add in antibiotics – a lot of antibiotics go out in a patients urine unchanged, for example, if you have a patient on cefepime at 6g a day, that’s basically going out 6g a day into that hospital’s wastewater – giving an advantage to bacteria that have genes of drug resistance. Then you also dispose of nutrients down those drains and all sorts of things and you can just see how it would be a superbug party!

I don’t know what’s going to need to happen for the greater community – there’s been research that’s shown that you can tell when a hospital is on a wastewater system because it tends to have more genes of drug resistance as it goes to wastewater treatment, so I think there are a lot of big issues that need to be tackled.

Martha: More broadly thinking about antibiotic resistance Amy gave us her opinion on the most promising strategies to tackle this global problem, as well as how the disparities between countries with different levels wastewater management could impact the emergence of resistance.

Amy: Antibiotic resistance as a global issue – I think there are a lot of moving parts going on. I think that we’ve been using antibiotics for the last 30–40 years pretty liberally, including in animal husbandry and patient care, and not really thinking too much or feeling too much the downsides of antibiotic usage. But bacteria have been around a lot longer than we have and even the antibiotic compounds most of them have been round a lot longer than we have, so it’s just a matter of organisms sharing those genes of drug resistance in response and so they can evolve a lot more quickly than a multi-celled organism – like us!

It [infection prevention]is probably a smaller role for the global issue but for the patient in the hospital it’s critical; it is central to preventing bad outcomes and preventing transmission to patients that are within the hospital. Does it change the overall rate at which genes of drug resistance are evolving and we’re losing antibiotics? Probably to some degree, but I think they’re kind of two synergistic elements. I think it’s really important for patients and healthcare workers within a hospital.

Martha: In lower resource countries that perhaps don’t have access to antibiotics properly – do you think stewardship and prevention is going to play a bigger role there?

Amy: I think if you don’t have wastewater treatment it is very difficult to have infection control have a huge impact. So what we don’t know everything that’s going on in countries that have genes of drug resistance but let’s take for example some of the antibiotic-resistant organisms that are evolving in South East Asia. What we see is that in countries like the USA (or countries that have wastewater treatment,) something like ESBLs are a minority or the enteric bacteria that carry genes that can hydrolyze some of our most important antibiotics are still quite rare in the community. Whereas if you pivot and you go to some of the data out of South East Asia, being in the hospital is not a risk factor for acquiring one of those organisms like it is in one of these higher income countries, and we’re now starting to see carbepenem resistance really affect patients and it’s really coming from the community because there’s just no barrier if you’re not doing wastewater treatment. All those things I described happening in a hospital plumbing system can happen in water or sewage where there’s intermixing.

I think the issues are going to be harder there – so then how do you do infection control to protect your patients? What I think is the most critical thing for developing countries that are facing this is we need to get them better drugs. Like you had said where they don’t have access to some of the newer agents I think we should put resources towards getting wastewater treatment for prevention but also that [lack of drugs]shouldn’t be the case. We should collectively decide that we’re not going to settle for ineffective drugs just because they’re [countries]not high-income. And that’s where getting those drugs to the patients is critical – they’ve got a tougher climb for infection control in those countries and where to put the resources.

Martha: Finally, I asked Amy what her vision was the future was, and where she hoped to see this field in the next 5 to 10 years’ time.

Amy: I think we need to continue to have discussions around what we’re going to do with hospital wastewater and its contribution to the evolution of antibiotic resistance. And who’s responsible – is it the hospital? Is it the wastewater management e.g. the EPA? Or is it public health? And it doesn’t matter who, we should all work together to work out how we’re going to minimize the impact from some of the inherent problems in hospital.

I also think that continuing to support antibiotic development is just going to be critical. Even if we could fix everything today, organisms are still going to evolve antibiotic resistance and we have lost some of our most important antibiotics and are going to continue to lose them. Things like ampicillin not working on E. coli anymore – that’s a really valuable drug. Organisms carry genes against ampicillin so frequently now; I think the microbiome of the world is forever changed. And so unfortunately I think we need to make sure we also have new agents, so 5–10 years from now we have several new classes of antibiotics.

Another thing that I’m hopeful for is that with advent and application of next-generation sequencing our ability to really understand the way that organisms are evolving and start tackling mobile genetic elements and mitigating rapid evolution and gene exchange in bacteria – small goals!

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