43. The Eye of the Storm

Contagious Conversations  /  Episode 43. The Eye of the Storm





Claire Stinson: Hello and welcome to Contagious Conversations. I'm Claire Stinson, host of today's conversation. Every episode, we hear from inspiring leaders and innovators who make the world healthier and safer for us all. Contagious Conversations is brought to you by the CDC Foundation, an independent nonprofit that builds partnerships to help the Centers for Disease Control and Prevention save and improve more lives.

Joining me today is Dr. Danielle Rankin, an epidemiologist for the Antimicrobial Resistance Team in the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention. Prior to pursuing her PhD, Dr. Rankin was an epidemiologist for the Florida Department of Health Healthcare Associated Infections Program. Dr. Rankin has published 28 manuscripts and throughout her career has conducted over 70 infection control assessments and investigated more than 60 domestic infectious disease outbreaks. In this episode, we explore the recent multi-state outbreak of a drug-resistant strain of pseudomonas aeruginosa linked to recalled eyedrops and CDC's role in the investigation.

Welcome, Dr. Rankin.

Dr. Rankin: Thank you for having me today.

Claire Stinson: We're really pleased to have you today and talk about this recent outbreak. So, CDC is collaborating with the Food and Drug Administration and state and local health departments to investigate a multi-state outbreak of a drug resistant strain of pseudomonas aeruginosa, as we just mentioned, linked to recalled eyedrops. When did CDC first learn about these infections?

Dr. Rankin: So first, I really think it's important to give a little bit of a background on the organism itself. So, our drug resistant strain of pseudomonas aeruginosa are typically seen in healthcare settings and can be spread from person to person through hand carriage of healthcare personnel or even from environment to patient when there are gaps in infection control practices during patient care activities. And prior to this investigation, we really have only seen one multi-state outbreak of pseudomonas aeruginosa, a drug resistant pseudomonas aeruginosa.

And to get to your question, we really initially learned of these infections between June through August 2022, when health department HAI and AR (healthcare associated infections and anti-microbial resistance) programs in three separate states reported clusters of pseudomonas producing the VIM carbapenemase. And what was interesting is that one of these clusters was a bit more unusual than we had previously seen because it involved eye infections in an ophthalmology clinic. And this was actually the first time carbapenemase producing pseudomonas aeruginosa from eye specimens had ever been reported to CDC. The other two initial clusters occurred at long-term care facilities and did not include patients with eye infections, but these infections were from other specimen sources.

Claire Stinson: So that's interesting. What led to discovering the bacteria being transmitted through eyedrops?

Dr. Rankin: That's a really great question. So here at CDC, we've actually increased funding for what we call whole genome sequencing. And we've helped guide public health laboratories to perform routine screening for uncommon multi-drug resistant organisms like VIM pseudomonas. So, from late September through early October, through the process of evaluating whole genome sequences associated with one of the outbreaks, we determined that the isolates from the three outbreaks as well as from individual patients from two separate states were caused from the same strain, which is VIM-80 GES-9 pseudomonas aeruginosa. And this ultimately led us to focusing on common products across facilities and sporadic cases. And the fact that we were actually seeing this rare strain across the United States in different body sites, that the bacteria was identified in different settings ,this led us to working closely with the HAI/AR programs to better understand the different exposure data that we had for this investigation. And so once we had this information, we were able to really focus on the methods to specifically identify common products, and in this case, the eyedrops, across healthcare facility clusters and sporadic cases.

Claire Stinson: That's really interesting and kind of scary to think about. So, people were getting sick, they were going blind and even dying from these infections. I'm sure there was incredible pressure to get to the bottom of this. What was your first big break in the investigation?

Dr. Rankin: Yeah, Claire, so you're exactly right. There was immense pressure to get to the bottom of this and really took countless hours of searching different product names to see if they had a manufacturer or even an ingredient in common. But if I had to take our first big break, it was really being able to go onsite in collaboration with Connecticut HAI/AR program, where we were able to actually conduct a match case control study in the facility cluster who, at the time, had the highest number of cases and was in a setting with patients on the same unit who didn't have VIM GES pseudomonas. And those patients were able to serve as our controls. And so what we did in this matched case control study, we had found that cases had five times greater odds of exposure to artificial tears than their controls. And this was surprising given that none of the cases at this facility had eye infections, but was also compelling in light of our previously mentioned cluster of the eye infections in a separate state.

And so going into the case control study a bit more, when we typically conduct these studies, we typically see odds ratios close to the null or 1.0. And so the fact that we observed such an elevated odds ratio, which as a reminder was five times, was huge and gave us confidence to really hone in on artificial tears in our investigation. So, in combination with the eye infections, this really helped us also obviously look further into those artificial tears. But really getting down to the bottom of the specific brand that was the source had its own challenges in itself. And to highlight on some of these challenges that we actually experienced, we determined not only individuals, but facilities use many different generic products of artificial tears and that these were not always tracked and documented and were essentially used interchangeably.

Claire Stinson: That's super interesting and sounds really complex and challenging. So, this type of bacterium has been around for years, but as you mentioned, it had not been seen in the United States before 2022. It is resistant to nearly all available treatments. What do we know about this bacterium and where it came from?

<p> Right. So, this outbreak strain is a type of resistant pseudomonas aeruginosa, which we have seen in the United States at a very low incidence and typically associated with healthcare facilities since I had mentioned before. But we've not seen this particular strain, as you just mentioned, prior to 2022. So, our current epidemiology and laboratory evidence really suggest that all of our cases of this strain in the United States likely were acquired from the recalled products. Although some cases may have also gotten this strain from patients who actually acquired this strain from the recalled products. And this is what we call secondary transmission. And so currently, FDA is conducting testing on the recalled artificial tear products to better understand the source of the outbreak. And to date, we have identified bacterial contamination from the artificial tear products, but the bacterial strains are still pending.

Claire Stinson: We'll be right back with Dr. Danielle Rankin.

Whether diseases start at home or abroad, CDC responds to America's most pressing health threats to keep the country safe and healthy. Learn more about CDC's role in disease investigations worldwide at www.cdc.gov.

And now back to our conversation with Dr. Rankin.

So, bacteria like these are constantly finding new ways to resist antibiotic treatments, which is concerning. Talk to us more about the causes of antibiotic resistance and what CDC is doing to address this issue.

Dr. Rankin: Thank you. And we know antibiotics and antifungals save lives, but their use can really contribute to the development of resistant germs. And because these organisms are able to develop defense strategies against antibiotics and antifungals, which is what we call resistant mechanisms. And so in order to combat antimicrobial resistance, CDC has invested in a national infrastructure to detect, respond, contain and prevent resistant infections across healthcare settings, communities, our food supply and even the environment, including the water and soil. And so this type of investment in the United States is through funding the HAI/AR programs in all 50 state health departments, Puerto Rico, Guam and the US Virgin Islands, where these HAI/AR programs perform surveillance and they conduct infection control assessments.

Claire Stinson: And just as a reminder to our listeners, when you say HAI/AR, so healthcare associated infections and then AR is anti-microbial resistance, correct?

Dr. Rankin: That is absolutely correct. Yes.

Claire Stinson: All right. Just as a reminder to our listeners.

Dr. Rankin: In addition, we also support Antimicrobial Resistance Laboratory Network where we provide nationwide laboratory capacity to rapidly detect antimicrobial resistance and inform local responses to prevent spread and protect the public. And really also, from this outbreak, it shows that this is not just a U.S. problem and that we're not only connected through travel, but we're also connected through trade. And antimicrobial resistance is also a global problem. And CDC, we also provide funding on a global scale and provide laboratory resources through the global antimicrobial resistance and laboratory network and also have a global action in healthcare network for antimicrobial resistance, which focuses on preventing the spread of highly resistant organisms in healthcare settings globally.

Claire Stinson: Thank you for explaining that. And I know that CDC says that a health threat anywhere is a health threat everywhere, and that certainly rings true here. So Dr. Rankin, when an outbreak like this occurs, can you detail for us what steps the CDC takes to investigate and head this off?

Dr. Rankin: Sure. So as you can imagine, there's actually quite a few steps that happen simultaneously, and I do want to preface that the order I detail these steps here are not necessarily the exact order or the steps that we use in every single outbreak investigation. So initially, as I reported, we do not always suspect a multi-state outbreak. Right? And as a team, we're assigned to different regions in which we provide assistance and collect basic epidemiology information on investigations from state and local HAI/AR programs that they're working on. And so based on the epidemiologic trends, we are seeing, we as a team will evaluate what we call signals and request additional bioinformatic analysis, or whole genome sequencing to determine if isolates are related.

And so once we identify a multi-state outbreak, we typically will hold a call with a state HAI/AR program or the programs that are involved in a multi-state outbreak. And during this call, we actually discuss the situation and we develop hypothesis generating questionnaires for the health departments to complete on their cases. And then we further analyze the data to determine similarities reported across the jurisdictions involved. And so from there, we're able to narrow in on the source, such as medical procedures performed at a facility or medical products. If we can't see any commonalities, we can also perform additional statistical analysis using case control studies, like in this case, we used a match case control study out in the field, to see if we're able to determine the source. And once this is performed, we then develop case report forms that are more specific. So in this case, we actually developed questions surrounding specific eye product questions, including questions about over-the-counter products like artificial tears.

Claire Stinson: So we mentioned earlier that CDC is working with partners in health departments on this investigation. Talk to us more about that and why are partnerships critical in solving outbreaks?

Dr. Rankin: Really without our partnerships and collaborations with the public health departments at the state and local level, investigating nationwide outbreaks and protecting patients from acquiring these highly resistant pathogens would be extremely challenging. So, what I'm saying is that the health departments really play an instrumental role in our multi-state outbreaks because they're what we call the boots on the ground. While we are working on a national scale to identify exposures in these multi-state outbreaks, health departments, specifically when this strain was identified in healthcare facilities, they were out in the field implementing measures to prevent secondary spread and were critical and were also critical in collecting and reporting exposure data to us.

Claire Stinson: It sounds like they were critically important. So, we know this is an ongoing investigation. As of May, this particular outbreak has involved 81 patients in 18 states and has caused four deaths. Where does the outbreak investigation stand today? And do any threats remain? Dr. Rankin: Yeah. So, the outbreak stands in what we refer to as a surveillance period where we have been identifying patients who either didn't discard the product and are still using it and have since developed infection, or more commonly, we've been identifying patients who are what we call epi-linked to other known VIM GES pseudomonas Orin cases in a healthcare facility, which is what I referred to at the beginning of the podcast as secondary transmission. And as a reminder, to really explain this is that VIM GES pseudomonas aeruginosa can be spread from person to person in healthcare facilities through hand care of healthcare personnel or even from environment to patient when there are gaps in infection controls such as hand hygiene.

And so when I think of any main threats, I really think of two, but they coincide a bit. One of the threats I think of is being that this pathogen can asymptomatically colonize a patient typically in the gut. And because of this, we know clinical cases we are seeing now are what we refer to as just the tip of the iceberg. And so the asymptomatic colonized cases are what are below the water surface of this iceberg. And because we don't systematically screen patients for this organism, it can go undetected until the patient develops an actual clinical infection where they have signs and symptoms. And because of this phenomenon, we will likely continue to see cases from this investigation for years. And so the second being that, again, from asymptomatic colonization is that we can see these resistant organisms, they will often unknowingly spread in healthcare facilities from person to person through shared medical equipment to person and environment to person and even plumbing to person. And so we may really continue to see secondary transmission within healthcare facilities and small clusters.

Claire Stinson: Thank you for explaining that. Such an interesting investigation. This is the first time I've heard of an outbreak spreading through eyedrops. Talk to us about the learnings from this outbreak. Has anything surprised you?

Dr. Rankin: Yeah, so seeing an outbreak spread through eyedrops is quite rare, as you mentioned. And there have been some bacterial contamination outbreaks linked to eye products, but this is the first outbreak in the United States of these highly resistant strains or antimicrobial resistant strains linked to a manufactured drug and really highlights the implications for spread. And then the other would be that the severity of these infections and the array of different types of infections shows that contaminated ophthalmic products can have severe health impacts, despite perceptions that over-the-counter products are lower risk than drugs that are delivered systemically.

And so while it may seem strange that there's a connection between eyedrops and these different types of infections, such as through sputum or the blood, there's actually a pretty simple explanation. And so the eyedrops are administered to the eye and the eye connects to the nasal cavity, and through the tear ducts, bacteria can move from the nasal cavity into the lungs where they can cause respiratory infections like pneumonia or be present for even extended periods without causing any signs or symptoms of illness, which is known as asymptomatic colonization. And bacteria that are present at these body sites can then seed infections at other sites such as blood or lungs. Claire Stinson: Super interesting. Thank you for explaining all of this. This is such an interesting and fascinating and complex investigation. So, we like to end on a positive note with our episodes. We know that antibiotic-resistant bacteria are a real public health threat, but what are the bright spots ahead in terms of how we are preparing to meet this challenge?

Dr. Rankin: Yeah. So, in this outbreak, it really demonstrated how investments in public health laboratories and health departments are addressing the antimicrobial challenges that we face. And through our recent initiatives to increase laboratory testing of HAI pathogens and performing whole genome sequencing, this directly led to the identification of this outbreak. And support for health departments to have dedicated staff for healthcare associated infections and antibiotic resistance has led to case investigations and actions to prevent further spread.

Claire Stinson: Fascinating. This has been a really important and interesting discussion about this ongoing investigation. Thank you for sharing all of your insights with us and thank you for being a part of Contagious Conversations.

Dr. Rankin: And thank you again for having me.

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