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Amesh A. Adalja, MD, FIDSA outlined the importance of recognizing antibiotic resistance in healthcare settings, educating patients on responsible antibiotic use, and the need for new treatments and diagnostic tools.

More Bugs, No Drugs: The Growing Threat of Antibiotic Resistance

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

Jacinda Abdul-Mutakabbir, PharmD, MPH, AAHIVP, discusses her work on the Equity in Antimicrobial Stewardship Efforts (EASE) framework

A Framework for Reducing Antimicrobial Stewardship Disparities

Jacinda Abdul-Mutakabbir, PharmD, MPH, AAHIVP, assistant professor of Clinical Pharmacy, University of California San Diego, was working with her research partner, Karen Tan, PhamD, BCIDP, assistant professor, Pharmacy Practice School of Pharmacy, Loma Linda University, and they discovered disparities in how antimicrobials were being prescribed across different racial and ethnic groups. Their study of disparities and social determinants expanded and developed into a framework around these findings.

“For us, it really became clear that there were not only racial and ethnic disparities, but disparities in terms of social vulnerability, disparities in terms of sexuality, and gender. And it really pushed us to think about how can we address these things?” recalled Abdul-Mutakabbir. “And we really developed our own set of steps for walking through how it is that we wanted to engage in the research. And we developed the [Equity in Antimicrobial Stewardship Efforts] (EASE) framework."

The framework is aimed at shining a light on inequities as it equates to antimicrobial prescribing practices and strategies to reduce them. She was part of a team that published a paper earlier this year that detailed the framework comprehensively in 

Antimicrobial Stewardship & Healthcare Epidemiology

Jasmine Marcelin, MD, FACP, FIDSA, associate professor, Department of Internal Medicine, associate medical director, Antimicrobial Stewardship Program, joined the project early on and stressed the importance of collecting data as a starting point.

“She always says you have to start with the data. You have to start with the numbers, because that is how we really investigate where the inequities exist,” Abdul-Mutakabbir said. "So I think for us, we had to start with our own data. Then we started to think, well, how do we grab the institution specific data? Then we thought we have to disaggregate the data based on areas of vulnerability. So, we started with race and ethnicity, and then we progressed to social vulnerability.”

For other institutions that are considering implementing the EASE framework, Abdul-Mutakabbir says to start small with a singular project.

“When you take on multiple areas, it can be hard to think about how to address each of these things adequately,” she said. "So, if in your hospital, you've noted potential disparities in racial and ethnic minoritized status start there. If you think about another area of a social determinant of health, maybe education, maybe language, start there. If you think about Medicaid use and sharing status, start there. So think about your population and what you see, then how it is that you should address those things moving forward.”

Jacinda Abdul-Mutakabbir, PharmD, MPH, AAHIVP, discusses her work on the Equity in Antimicrobial Stewardship Efforts (EASE) framework, including progress for it, and how other institutions or providers can implement it. 

Daniel B. Chastain, PharmD, BCIDP, AAHIVP, FIDSA, reviews the data of this class of therapies and how it may be clinically beneficial.  

Considering a Beta Lactam as Adjunctive Therapy for Staphylococcus aureus Early in Treatment 

It has been documented that the incidence rates for 

 bacteremia (SAB) ranges from 20 to 50 cases/100,000 population per year, and the mortality rates are between 10% and 30%.

According to one study, this accounts for a greater number of deaths than for several other infectious diseases including AIDS, tuberculosis, and viral hepatitis combined.

This infection can be particularly challenging on seniors as age is the largest factor for mortality with older patients more than twice as likely to expire from SAB.

“One of the things that I've always heard and always been taught is respect 

 bacteremia, in that it's always challenging, and it's certainly a difficult process [treating it], said Daniel B. Chastain, PharmD, BCIDP, AAHIVP, FIDSA clinical associate professor University of Georgia College of Pharmacy.

 can also be heterogenous in presentation and lead to patient management issues. 

Chastain reviewed the literature looking at the use of beta-lactams as adjunctive therapy for 

, and presented his findings at IDWeek last month.

One of the novel approaches is to consider prescribing combination therapy earlier in the treatment cycle.

“Given the presentation, given the severity of the illness, why not add combination therapy up front? Once you have a blood culture that has staphylococcus species before you know that it's MSSA or MRSA, there are certainly some older data that supports a beta-lactams from start to finish, having improved outcomes compared to deescalating from vancomycin to a beta-lactam,” Chastain said. “So if we could start with vancomycin, adaptomycin, in addition to either a cefazolin or an antistaphylococci penicillin, perhaps we're able to better impact that patient's care up front and maybe decrease the risk of complicated 

He sees another potential benefit in risk stratification looking at patient presentation, which may help identify who would be a better candidate for combination therapy. Chastain notes there does not appear to be a reduction in mortality in the literature. “Most of them don't result in mortality benefit, which is really interesting, despite improvements in time to blood culture sterilization or decreased risk of recurrence or persistent 

“I think the lack of mortality benefit is largely from the fact that most of our clinical trials that we have now include a wide variety of patients with diverse sources. So some may have catheter-related infections; whereas others may have bone or joint involvement. Some may have endovascular [infections], so if we're able to better risk stratify, perhaps upfront, through biomarkers or certain sub phenotypes, then perhaps, maybe we can better affect their care overall, and actually figure out who could benefit from that combination therapy.”

He does believe in exercising caution when considering adjunctive therapy.

“I think that of the data that we have, early combination therapy for patients that are at high risk for poor outcomes, so high risk for complicated 

bacteremia or high risk for mortality, will hopefully certainly improve patient outcomes,” Chastain said. “And then the only thing I would add is that there are some door framework and radar analysis that have been done to suggest that perhaps patients don't always have the greatest experience with combination therapy. So, I think it's important that we balance being a little bit more aggressive with treatment as well as what the patient experiences, and taking that whole entire process into account as we try to treat these patients.”

1.van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. 

. 2012;25(2):362-386. doi:10.1128/CMR.05022-11
2. Chastain D. Beta-Lactam Adjunctive Therapy for Difficult 

 Infections. Presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

This bacteremia can present heterogeneously and be difficult to contain, especially in an older patient population. Daniel B. Chastain, PharmD, BCIDP, AAHIVP, FIDSA, reviews the data of this class of therapies and how it may be clinically beneficial in combination with other antimicrobials.

Clinical Corner 

At the ongoing The Liver Meeting in San Diego, Atea Pharmaceuticals has presented posters about the company’s investigational antiviral combination of bemnifosbuvir and ruzasvir, which is being studied for potential 

 treatment. In one of the posters, the combination therapy achieved a 97% sustained virologic response at 12 weeks post-treatment (SVR12) in a phase 2 lead-in cohort. According to the investigators, the analysis supports a short 8-week treatment with bemnifosbuvir and ruzasvir for chronic HCV.

A multiscale HCV viral kinetic model was utilized to estimate the clinical effectiveness of the combination of bemnifosbuvir and ruzasvir in blocking HCV replication and viral assembly/secretion against HCV. This model evaluated the combination of bemnifosbuvir and ruzasvir in the lead-in cohort (n=60) of a Phase 2 single-arm study. This cohort was comprised of treatment-naïve, non-cirrhotic patients with chronic HCV receiving 550 mg bemnifosbuvir once daily (QD) and 180 mg ruzasvir QD for 8 weeks. The multiscale model was fit to the plasma viral load (VL) and the alanine aminotransferase (ALT) data from all 60 subjects simultaneously through mixed-effects population fitting.

“A multiscale model of HCV infection and treatment was designed to estimate the 

effectiveness of agents including various combinations of direct-acting antivirals to block HCV replication and viral assembly,” Alan Perelson, PhD, senior fellow at Los Alamos National Laboratory, said in a statement. “The data presented today modeling the combination of bemnifosbuvir and ruzasvir for the treatment of HCV align with the reported clinical results from the lead-in cohort of the Phase 2 study. These data are highly encouraging.”

The modeling results provided insight on the mechanism of action and demonstrated that the combination of bemnifosbuvir and ruzasvir was highly effective in blocking both viral replication and viral assembly/secretion in HCV-infected patients, independent of genotype, age, sex, or fibrosis score.

According to the company, bemnifosbuvir has been shown in 

 studies to be approximately 10-fold more active than sofosbuvir (SOF), against a panel of laboratory strains and clinical isolates of HCV GT 1–5. 

 studies have also demonstrated bemnifosbuvir remained fully active against SOF resistance-associated substitutions (S282T), with up to 58-fold more potency than SOF.

The pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV. Bemnifosbuvir has been shown to have a low risk for drug-drug interactions. Bemnifosbuvir has been administered to over 2,200 subjects and has been well-tolerated at doses up to 550 mg for durations up to 12 weeks in healthy subjects and patients.

The other half of the combination, ruzasvir, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. Ruzasvir has been administered to over 1,500 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The PK profile of ruzasvir supports once-daily dosing.

Atea is a Boston-based, clinical-stage biopharmaceutical company engaged in the development of oral antiviral therapeutics for viral diseases. They also have an investigational COVID-19 therapy in clinical trials.

1.Ribeiro R. Multiscale Modeling of Lead-in Results from a Phase 2 Study of an 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection. Poster #1467 presented at The Liver Meeting. November 15-19, 2024. San Diego, CA.
2. Atea Pharmaceuticals Presents Multiple New Datasets Supporting the Combination of Bemnifosbuvir and Ruzasvir for the Treatment of Hepatitis C Virus at AASLD’s The Liver Meeting 2024. Atea Pharmaceuticals press release. November 15, 2024. Accessed November 19, 2024.
https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-presents-multiple-new-datasets-supporting

Atea Pharmaceuticals has been reporting data on its combination of bemnifosbuvir and ruzasvir as a potential treatment for the virus.

Investigational Combination Hepatitis C Therapy Demonstrates a 97% Sustained Virologic Response

With melting ice and the release of ancient pathogens, there are concerns around the emergence of potentially unknown infectious diseases

Will the Melting Permafrost Uncover Vector Borne and Zoonotic Pathogens and Release Ancient Infectious Diseases? 

For years, increased temperatures have been leading to climate change and concerns around rising ocean temperatures and glaciers melting and creating sea rise. Another less discussed climate concern has been the melting permafrost on land and the potential release of zoonotic and vector borne pathogens into the environment.

There are unique discoveries of extinct animals and other organisms from thousands of years ago being made today in the Arctic. In 2020, for example, investigators in Siberia stumbled upon a saber tooth cub, which they estimated to be 32,000 years old, was uncovered and it remained intact.

Additionally, in Siberia, researchers uncovered what has been referred to as “zombie viruses.” 

“We report the preliminary characterizations of 13 new viruses isolated from 7 different ancient Siberian permafrost samples, 1 from the Lena river and 1 from Kamchatka cryosol. As expected from the host specificity imposed by our protocol, these viruses belong to 5 different clades infecting 

. but not previously revived from permafrost: Pandoravirus, Cedratvirus, Megavirus, and Pacmanvirus, in addition to a new Pithovirus strain, which are characterized as viruses that have inactive for thousands of years,” investigators reported.

“There's certainly been a lot of interest in recent times, and a lot of publicity around things like zombie viruses. So there's no easy answer to that. I think to start with, there are people giving this quite a lot of attention right now, certainly in the scientific world, also in the risk assessment world, and that includes things like national security,” said Emily Jenkins PhD, DVM, BScHon, professor and graduate chair, Department of Veterinary Microbiology, and head of the Zoonotic Parasite Research Unit at the Western College of Veterinary Medicine at the University of Saskatchewan, Saskatoon, Canada. “What we can say is that there's not a whole lot of evidence of spontaneous reemergence from the tundra right now.”

She does say the potential jump of these ancient viruses into humans and animals is still a very difficult transmission, especially as these pathogens may not survive.

“There was a nematode resuscitated from permafrost and was alive, a 40,000 year old roundworm. One thing to think about is that free living organisms are designed to survive more in the environment than pathogens,” Jenkins said. “Like the roundworms, are those so called zombie viruses. They're actually not pathogens of people or even animals.They're either free living or the viruses in particular, were actually viruses of amoeba. So it is quite a big stretch to jump from those things surviving to pathogens. The risk is not zero, but it's low probability.”

Polar Bears: The Proverbial Canary in the Coal Mine?

Jenkins has been studying organisms and animals in the melting permafrost and says there is evidence that can be gleaned from work with polar bears.

“We had this treasure trove of archived polar bear serum that stretched from the 80s, 90s, to the 2010s," Jenkins said. “We were able to take that set of sera and test it for exposure to a whole range of pathogens, including toxoplasma. We showed that over those decades, the amount of polar bears getting exposed was higher and higher—probably as a result of them losing sea ice, spending more time on land, and being more exposed to terrestrial pathogens.”

However, although nothing of concern has arisen from this in terms of older pathogens, she points to climate change issues affecting the Arctic, and the emergence of the modern-day vector borne viruses that could be a greater concern. 

“One of the groups of pathogens we know are going to change with climate change is vectors and vector borne diseases. Some of the work that we did on those polar bear blood samples showed that they were increasingly exposed to these vector borne or mosquito borne diseases as they spent more time on land,” Jenkins said. “And interestingly, the female polar bears, when they're pregnant, they spend 8 months on land, vs the males, who only spend 3 months on land. So the females were way more exposed to these vector borne viruses. And when we started looking across the North American Arctic, from Alaska to Greenland, sure enough, these particular vector borne viruses, which people don't think of the Arctic as this hotbed of vector borne disease, but they were present in mosquitoes all the way from Alaska to Greenland. So that's another significant potential outcome of climate change: increased numbers of vectors that develop and more rapid development of both the vectors and the viruses.”

Jenkins spoke at the recent IDWeek on this topic and says the environment is the biggest driver of changes and influences humans, animals, and pathogens.

"So recognizing that the drivers are much bigger than us and our animals and wildlife is, I think, the message of One Health—which is that we're all in this together. Environment is driving massive changes, and we have some tools in our toolkit that we didn't used to have, in terms of surveillance and interventions. So I'm hopeful that One Health offers not the magic solution, but a solution to some of these really increasingly pressing challenges, especially as we see the climate change crisis and human health and socioeconomic crises all coming together globally.

1.Black R. The world’s first saber-toothed cat mummy has been found in Siberia. 

 November 19, 2024. Accessed November 28, 2024.
https://www.nationalgeographic.com/science/article/sabertooth-cat-mummy-first-cub.
2.Alempic JM, et al. An update on eukaryotic viruses revived from ancient permafrost. Biorxiv. February 2, 2023. Accessed November 28, 2024.
https://www.biorxiv.org/content/10.1101/2022.11.10.515937v2
3.Jenkins E.A One Health understanding of shifting zoonoses in the Arctic. Presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

With melting ice and the release of ancient viruses, there are concerns around the emergence of potentially unknown infectious diseases. Emily Jenkins PhD, DVM, BScHon, offers insights on “zombie viruses” and says polar bears might hold the key to understanding what lies ahead, and how a One Health approach may help in surveillance and prevention.

Bruce Jones, PharmD, FIDSA, BCPS offered clinical considerations for the concerns around infective endocarditis and when choosing empiric therapy.

Treatment Considerations for Empiric Therapy

 bacteremia remains a serious infection that can lead to infective endocarditis, and a higher mortality rate. With this in mind, what do you want to consider in treatment options?

, I think of a pathogen with metastatic tendencies; it often spreads to distant sites and tends to form abscesses. For us, we used to assume MRSA until proven otherwise if 

 was in our differential. Around 2015, things changed with the introduction of multiplex PCR—specifically Biofire at our institution—which was a game-changer for managing bacteremia. This tool allows us to quickly identify MRSA versus MSSA, and even detect 

 itself very early on, which helps guide treatment decisions upfront.

Another key point I emphasize is beginning with the end in mind, particularly regarding OPAT. Many of these patients will need 4 to 6 weeks of treatment, so from a discharge and OPAT perspective, it's crucial to make these decisions early, ideally well before discharge. Often, we tend to wait until the last moment, but it’s better to evaluate these factors early in the admission.

What are your clinical considerations when choosing an empiric therapy for these patients?

 Clinical stability is our top priority. For a very sick patient in the ICU on multiple pressors, we approach aggressively upfront, as 

 infections carry a high mortality rate. Our goal is to get the infection under control as quickly as possible.

We also consider the suspected source of the infection. For example, when MRSA is suspected, if it's a respiratory source, we might avoid using daptomycin. Comorbidities play a big role as well; renal function is one of the first things we assess, especially when considering vancomycin in patients with acute kidney injury or chronic kidney disease.

Once we know whether it's MSSA or MRSA—thanks to rapid diagnostics—we tailor treatment accordingly. For MSSA, cefazolin or an antistaphylococcal penicillin is our go-to. For MRSA, we often consider vancomycin or daptomycin, though we've used less vancomycin in the past year or two and more daptomycin instead. While our use of linezolid has been slower to increase, it's still an option. We're also starting to see some off-label use of ceftaroline, and with the release of septiviprol, we’ll soon have another tool in our toolkit.

The conversation was edited for grammar and clarity.

Amesh A. Adalja, MD, FIDSA

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