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CEO of Lopoxy Therapeutics and Clinical Scientist.

CEO Larry Sutton, MD, PhD, discusses SIDIPREV, a novel oxygen-based therapy aimed at preventing C difficile infections.

Fighting C difficile Before It Starts: Lopoxy Therapeutics Approach

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

The National Institutes of Health (NIH) updated its risk assessment for highly pathogenic H5N1 avian influenza A virus (HPAI H5N1) saying the risk to the general public remains low.

The NIH’s National Institute of Allergy and Infectious Diseases (NIAID) leadership including NIAID Director Jeanne M. Marrazzo, MD, MPH, and Michael G. Ison, MD, MS, chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases said in a new commentary published in the 

, that people should find a balance between enhanced vigilance and “business as usual” with respect to avian influenza.

In the commentary, they discuss 4 strategies in how we can respond to the threat including:

1. “Collaboration among investigators in human and veterinary medicine, public health leadership, health care providers, and occupational authorities;

2. the urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission;

3. pursue development and testing of medical countermeasures; and

4. precautions to prevent infection are critical, including the use and optimization of PPE in occupational settings and education about the risk of contact with sick birds and animals.” 

(See below for some infection prevention strategies from Marrazzo.)

Thus far, the overwhelming majority of cases have been in farm workers who are working with cattle and poultry. All cases in the United States, except 1 have been classified as mild. The single case of severe avian influenza has been reported in a 65-year old person who had a different genotype of the virus, D11.

commentary, Marrazzo and Ison point out a case in Canada of a young girl who also had the D11 genotype and was hospitalized with a very severe case including having to be put on venovenous extracorporeal membrane oxygenation (ECMO). She had existing mild asthma and obesity and presented with conjunctivitis and fever and had progression to respiratory failure. After ECMO and treatment with antivirals, she recovered.

As of today, January 3, 2025, there have been 66 cases of avian influenza in the US according to the CDC’s website. And the agency points out there have only been zoonotic transmissions in humans and no human to human transmission. 

 recently who offered infection control prevention strategies for both farm workers and the general public.

“The CDC recommends avoiding direct contact with wild birds or other wild animals, especially if they appear to be sick or dead. Wild birds can also be infected with H5N1 and not appear sick, so it is better to observe them from a distance. People who live and work alongside domesticated animals which may be potentially infected, such as poultry or dairy cattle, can take extra precautions to avoid contact with infected animals and their contaminated environments. For example, wearing personal protective equipment can help dairy farm workers reduce exposure to infectious milk,” Marrazzo said.

“While there are no documented cases of humans directly catching H5N1 influenza from drinking raw unpasteurized milk, raw milk produced by cattle infected with H5N1 contains high levels of the virus. Fortunately, pasteurization appears to kill the flu virus. Because of the risk of exposure to the H5N1 flu virus, as well as other harmful diseases, people should not consume raw milk or products, such as fresh cheese, that are made with raw milk.”

In their commentary, Marrazo and Ison succinctly offer their assessment of where we are today at the beginning of 2025 as it regards to this strain of influenza.

“The CDC still designates the risk of HPAI A(H5N1) to most Americans as low. We do have candidate vaccines and antivirals available to try to mitigate severe influenza in the case of wider spread… The past weeks have seen more cases detected in more states as well as more persons with respiratory illness acquired through exposure to poultry or from an unknown source. Without a clearer understanding of the extent of exposure, infection, viral evolution, and transmission, we will be unable to properly protect our communities from a pathogen that has proven to be a formidable challenge to human and animal health,” they write.

1.Ison MG, Marrazzo J. The Emerging Threat of H5N1 to Human Health. 

. Published online December 31, 2024. doi:10.1056/NEJMe2416323
2. Parkinson J. CDC: Genetic Mutations of Avian Influenza Emerge in First Severe US Case Contagion. December 28, 2024. Accessed January 3, 2025. 


https://www.contagionlive.com/view/nih-mutation-in-avian-influenza-protein-could-enable-easier-human-infection-but-risk-of-infection-remains-low


3. H5 Bird Flu: Current Situation. CDC. January 3, 2025. Accessed January 3, 2025.
https://www.cdc.gov/bird-flu/situation-summary/index.html

The federal health agency stresses the importance of finding the balance between vigilance and enjoying normal activities. 

NIH Offers Updated Risk Assessment on Avian Influenza

In the United States, there are approximately 2 million outpatient visits related to community-acquired pneumonia (CAP) in the pediatric population as well as approximately 124,000 hospitalizations for children, annually.

 And CAP continues to be one of the most common reasons for hospitalizations in this patient group.

With concerns around CAP hospitalizations, investigators from the Children's Hospital of Philadelphia (CHOP) studied an intervention utilizing clinician feedback reports to evaluate the appropriate usage for antibiotics for CAP inpatients.

Typically, in the outpatient pediatric setting, these feedback reports have been used as a stewardship tool looking at individual performance says, study first author Kathleen Chiotos, MD, MSCE, assistant professor of Anesthesiology, Critical Care, and Pediatrics at the University of Pennsylvania Perelman School of Medicine and an attending physician in Critical Care Medicine and Infectious Diseases at CHOP. She explained using these reports in the inpatient setting and including group-level performances were novel concepts.

Chiotos said audit and feedback reports were generated monthly using a previously validated algorithm to both identify patients with CAP and discuss the antibiotic use.

“We delivered the reports both by email as well as during a monthly quality improvement meeting with our hospital medicine clinicians, which allowed for discussion around the report and recommendations for optimal management of CAP,” Chiotos said in an interview with 

The intervention showed increased improvement in clinician adherence to antibiotic recommendations. “Preintervention, 213 of 413 (52%) encounters received the appropriate antibiotic choice and duration, which increased to 308 of 387 (80%) postintervention,” the investigators wrote.

The investigators’ analysis demonstrated an 18% increase in adherence without any significant changes over time. Although there were no differences in the length of stay or hospital revisits, Chiotos points out the importance of the overall study.

"We showed that there was no difference in the rate of revisits or readmissions and that there was a slightly shorter length of stay during the post-intervention period, when antibiotic durations were shorter,” Chiotos said. “While not better outcomes per se, the fact that kids do just as well with a shorter duration and are at less risk of side effects is an important finding and a win for our patients.”

The investigators conducted a “quasi-experimental study” between December 2021 and November 2023 within CHOP. They used an “interrupted time series analysis (ITSA) to estimate the immediate change and change over time in the proportion of CAP encounters adherent to validated metrics of antibiotic choice and duration, then used Poisson regression to estimate intervention effect as a rate ratio (RR).” 

The investigators determined the specific antibiotic and duration using only data from the electronic health record (EHR). "Appropriate antibiotic choice was defined as administration of amoxicillin or ampicillin within the first 48 hours. If the patient was admitted to the PICU or had a concurrent diagnosis code for empyema or lung abscess, ceftriaxone was also considered appropriate. If the patient had a history of methicillin-resistant 

 (MRSA) infection or colonization within the preceding one year, any anti-MRSA antibiotic was also considered appropriate. For patients with reported beta-lactam allergy or beta-lactam antibiotic use within the preceding 28 days, any antibiotic was considered appropriate," the investigators wrote.

In addition to determining the right antibiotic and duration, Chiotos believes this novel application could be utilized further. “Because we were able to derive definitions for CAP as well as for appropriate antibiotic use using only data from the electronic health record—as opposed to manually reviewing charts—utilizing feedback reports such as these may be more feasible for stewardship programs.”

References
1. Katz SE, Williams DJ. Pediatric Community-Acquired Pneumonia in the United States: Changing Epidemiology, Diagnostic and Therapeutic Challenges, and Areas for Future Research. 

. 2018;32(1):47-63. doi:10.1016/j.idc.2017.11.002
2. Chiotos K, Dutcher L, Grundmeier RW, et al. Impact of clinician feedback reports on antibiotic use in children hospitalized with community-acquired pneumonia. 

. Published online December 3, 2024. doi:10.1093/cid/ciae593



Data detailing antibiotic choice and duration derived from electronic health records improved appropriate therapy use for community-acquired pneumonia. 

Clinician Feedback Reports on Antibiotics Shape Usage in Pediatric Inpatients With Pneumonia 

Exploring the challenges and strategies for combating MDR Pseudomonas aeruginosa infections, as discussed with Jason Pogue, PharmD, BCPS, BCIDP

Emerging Resistance in Pseudomonas Treatment: Key Insights from the CACTUS Study

, compared the effectiveness of ceftolozane-tazobactam (CT) and ceftazidime-avibactam (CZA) in treating multidrug-resistant (

 infections. The study found that both treatments had similar clinical outcomes. Of the 234 patients treated with CT, 

, compared to 55% for those treated with CZA. The 30-day mortality rates were also similar: 20% for CT and 19% for CZA.

In the final part of our interview with Jason M Pogue, PharmD, BCPS, BCIDP, clinical professor at the University of Michigan and investigator of the study, we discussed the high rates of emergent resistance observed in Pseudomonas treatments. Resistance developed in 1 in 5 patients, regardless of the treatment arm. Pogue noted that 

 resistance is driven by upregulated chromosomal mechanisms, rather than by transferable beta-lactamases. This type of resistance is more common in clinical settings where traditional agents like cefepime, meropenem, and piperacillin-tazobactam (piptazo) are not used, as these drugs often contribute to elevated resistance levels.

When asked about the high rates of resistance observed, Pogue emphasized the nature of 

 as a particularly challenging pathogen. He explained that the resistance seen with newer agents like CT and CZA is not unexpected, given the bacteria's ability to upregulate chromosomal resistance mechanisms.

“When we sat and looked at these results, when we first got them, we started thinking through them. This is what jumped out to us first: Regardless of what treatment arm you were in, you're giving this novel, or I guess at least novel-ish, since they're like, 10 years old now, novel agents for resistant 

, and one out of every five times in both arms, you're seeing resistance development.”

 is a jerk. I don't know how else to say this—it's kind of the nature of 

He further explained the biological mechanisms behind this resistance, "What's unique about 

 is a lot of the beta-lactam resistance that we see is driven by upregulation of chromosomal mechanisms of resistance. So, rather than passing beta-lactamases from one to another, the resistance is in the chromosome of the organism. And in the presence of certain things, notably antibiotics, you can see upregulation of these resistance mechanisms.”

Building on this, he clarified why resistance development should be viewed in the context of treatment settings, "It’s not shocking that this happens because, when you're using these drugs, you're already in a situation where resistance is present in the background. You’re just kind of taking it to the next level with these agents. And I think it’s important for us to think about the fact that this happens 1 out of 5 times. That’s kind of the nature of Pseudomonas.”

Pogue’s insight reveals why resistance remains a challenge even with newer agents like CT and CZA: 

’s ability to adapt and upregulate its resistance mechanisms makes it difficult to achieve long-term success with many treatments.

 resistance is not new, nor is it specific to the newer beta-lactam agents. Historically, carbapenems have been associated with resistance development in about 20% of patients, and there is limited data on the resistance patterns seen with piptazo and cefepime.


“If you look historically at the carbapenems, they cause resistance in 20% of patients. Not a lot of good data out there on piptazo and cefepime, but just as a clinician, those of you watching know that it’s not shocking when you treat a patient for 

 and they develop resistance. That’s kind of the nature of the beast,” This emphasizes that 

resistance is a longstanding issue in clinical practice, and resistance development remains common even with first-line antibiotics.

Despite the high rates of resistance observed in the study, Pogue emphasized that strategies exist to help mitigate its emergence. He discussed potential avenues for improving treatment outcomes, including dose optimization, combination therapy, and exploring adjunctive therapies.
"One of the things we’ll want to do moving forward, and as a community, we need to do, is ask: “Are there strategies that can limit the emergence of resistance?” Whether that’s dose optimization, whether that’s robustly comparing combination therapy to monotherapy, or some sort of adjunctive therapy, I think those are next steps. And it just shows you the need for continued drug development in this space as well.”

Pogue’s focus on exploring these strategies highlights the importance of finding new ways to manage and reduce resistance. He also stressed that continued innovation in antibiotic development is essential for staying ahead of evolving bacterial threats like 

The findings of the CACTUS Study offer valuable insights into the challenges of treating MDR 

 infections, highlighting the ongoing issue of resistance. While the clinical success rates for CT and CZA were similar, the development of resistance in 1 in 5 patients remains a key concern. Pogue’s recommendations to optimize dosing, explore combination therapies, and continue drug development will be crucial for addressing these issues moving forward.

Part 1 of our interview introducing The CACTUS study: 

CACTUS Study Compares Ceftolozane-Tazobactam vs. Ceftazidime-Avibactam for MDR Pseudomonas

Part 2 of our interview discussing ceftolozane tazobactam’s effectiveness over ceftazidime avibactam: 

Ceftolozane Tazobactam Linked to Increased Clinical Success in Pneumonia

Shields RK, Abbo LM, Ackley R, et al. 1109. A multicenter, observational study to compare the effectiveness of Ceftazidime-Avibactam versus Ceftolozane-Tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the United States (CACTUS). Open Forum Infect Dis. 2023;10(Suppl 2):ofad500.082. Published 2023 Nov 27. doi:10.1093/ofid/ofad500.082

In 2024, there were many news updates in the world of respiratory infections, ranging from updates in vaccinations to new data on the long-term effects of some of these illnesses on patients. The 

 team followed it all, and spent our time speaking with experts from major institutions, pharmaceutical companies, and the federal agencies who are working together to push medical science forward.

Here, we'll be providing a list of stories that resonated with our audience in 2024 in the area of respiratory infections. As expected, a number of COVID-related updates made their way into this list, among other news items that were of interest to readers. 

Click the headlines to read more from these stories.

During the Pandemic, 75% of Hospitalized COVID-19 Patients Received Antibiotics, Despite Only a Minority Needing Them

In the early days of the pandemic when hospital ICUs were filling up with severe COVID-19 patients, clinicians had no therapeutic agents, and no one had any form of immunity to fight the virus, thus health care turned to a familiar form of treatment: antibiotics.

New data from the WHO offers further information on the scope of this treatment challenge that happened in the first years of the pandemic.

Although only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, 75% of patients were treated with antibiotics ‘just in case’ they helped, according to the WHO research. The highest rate of antibiotic use was seen among patients with severe or critical COVID-19...

COVID-19 Vaccination Associated with Reduced Risks of Thromboembolic, Cardiovascular Complications

One of the ongoing concerns of COVID-19 vaccines has been reports around thromboembolic and cardiovascular events. There have been reports of blood clots following adenovirus-based COVID-19 vaccines, with an association that was further assessed in observational studies. Later on, mRNA-based vaccines were found to be associated with the risk of rare myocarditis events. Contrary to these past associations, a new study published in the journal, 

, reported there was a major reduction of risk (45–81%) for post-acute COVID-19 venous thromboembolism (VTE), arterial thrombosis/thromboembolism (ATE) and heart failure (HF) in patients who had been vaccinated...

Healthcare Workers Who Received Additional Vaccine Dose Had Lower Odds of Symptoms at 6 Weeks

The early days of the Omicron predominant period continued to see high incidence rates of COVID-19 that included severe infections, hospitalizations, and mortality. For their part, healthcare workers (HCWs) were always in close proximity to patients with severe infection, and consequently in harm’s way. As such, HCWs saw a large incidence rate of active infection as a population.

According to 1 study done in the early period of the pandemic beginning from the time no vaccines were authorized, and extending through until nearly a year after the vaccines had been initially rolled out (December 2020), HCWs took up a large percentage of confirmed cases...

The US Will Transition to Trivalent Vaccines for Next Year's Influenza Season

The FDA’s Vaccines and Related Biological Products Advisory Committee recommended that all US flu vaccines transition from quadrivalent to trivalent vaccines for the 2024-2025 flu season. The trivalent vaccines’ formula will still contain the influenza A(H1N1), A(H3N2), and B/Victoria-lineage vaccine virus, but omit the influenza B/Yamagata virus because it is no longer actively circulating.

“FDA has been engaging and interacting with manufacturers of FDA-approved seasonal flu vaccines and providing scientific and regulatory advice to them to facilitate the timely availability of approved safe and effective trivalent seasonal flu vaccines for the 2024-2025 US flu season,” said the FDA in a news release...

COVID-19 Vaccination During Early Pandemic Years Shown to Reduce Risk for Heart Attacks, Strokes

The incidence rates for both heart attacks and strokes (arterial thromboses) were lower after COVID-19 vaccination than before or without vaccination during the earlier years of the pandemic, according to a new study from England.

Heart attacks and strokes were up to 10% lower in the 13 to 24 weeks after the first dose of a COVID-19 vaccine. And post-second dose, the incidence was up to 27% lower after receiving the AstraZeneca vaccine and up to 20% lower after the Pfizer/Biotech vaccine...

Japan Approves Updated Self-Amplifying mRNA COVID-19 Vaccine

Japan has approved the CSL and Arcturus Therapeutics' Updated self-amplifying (SA) mRNA COVID-19 Vaccine, ARCT-154 (Kostaive). The updated vaccine is targeted to protect against the JN1 lineage of omicron subvariants for adults 18 years of age and older. "We are pleased to receive the updated approval from Japan's Ministry of Health, Labor and Welfare, and remain on track to distribute Kostaive in time for the October COVID-19 vaccination campaign," Emmanuelle Lecomte-Brisset, senior vice president and head of Global Regulatory Affairs, CSL, said in a statement...

In a retrospective cohort study published in 

As 2024 winds to a close, take a look back on some of the biggest stories Contagion was following around respiratory infections.

Larry Sutton, MD, PhD

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