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Panelists hypothesize on theoretical downsides of resistance development for gram-negative infections and reflect on the importance of implementing outpatient parenteral antibiotic therapy.

ABSSSI and OPAT: Key Messages

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

LPOXY Therapeutics, Inc, has announced a $28 million Series A financing agreement with 5 Horizons Ventures to fund the pivotal STOP-Cdiff study. The trial will evaluate Sidiprev, a first-in-class, nonantibiotic therapy designed to prevent 

 infections (CDI), which the Centers for Disease Control and Prevention classifies as an urgent public health threat causing approximately 80 deaths daily in the United States.

The STOP-Cdiff trial will be a randomized, placebo-controlled superiority study enrolling approximately 500 hospitalized patients at elevated risk for CDI due to age and antibiotic exposure. Conducted under the US Food and Drug Administration (FDA)'s Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD), the trial is intended to serve as the registrational study for Sisiprev. LPOXY anticipates trial initiation in the third quarter of 2026, with a regulatory filing projected for 2029.

Sidiprev is formulated as an orally administered, enteric-coated capsule that delivers a controlled release of oxygen into the lower gastrointestinal tract. The oxygen-rich environment is designed to inhibit anaerobic pathogens such as 

. Additional mechanisms may include suppression of toxin production and mucosal anti-inflammatory effects.

 remains a leading cause of health care–associated infections, particularly among hospitalized patients receiving antibiotics. No therapies are currently approved to prevent primary CDI. Preventive approaches that avoid antibiotic use are considered critical to address antimicrobial resistance and health care costs associated with CDI-related complications.


In January 2025, LPOXY announced the acquisition of key assets from Xeno Biosciences to support Sidiprev development. The acquisition included regulatory filings; FDA correspondence; chemistry, manufacturing, and control data; intellectual property; and results from phase 1 and 1b studies demonstrating safety of the active pharmaceutical ingredient.

At that time, Larry D. Sutton, MD, PhD, CEO of LPOXY, explained in an interview that Sidiprev delivers oxygen into the gastrointestinal tract, a mechanism toxic to anaerobic 

. Proposed additional effects include suppression of toxin production, enhancement of immune clearance, and modulation of the gut microbiome to reduce spore germination. Sutton noted that, unlike vaccine-based approaches that did not meet efficacy end points in late-stage trials, Sidiprev is designed for coadministration with antibiotics, the primary risk factor for CDI, to prevent infections before onset.

LPOXY has indicated plans to use LPAD to target high-risk populations, such as older adults hospitalized with community-acquired pneumonia who are treated with broad-spectrum antibiotics. The company has also reported ongoing efforts to establish partnerships to expand hospital access and distribution once the therapy progresses through pivotal trials.

1. LPOXY initiates $28M Series A financing with 5 Horizons Ventures to fund STOP-Cdiff pivotal trial. News release. LPOXY Therapeutics Inc. September 3, 2025. Accessed September 4, 2025. 

https://www.prnewswire.com/news-releases/lpoxy-initiates-28m-series-a-financing-with-5-horizons-ventures-to-fund-stop-cdiff-pivotal-trial-302543122.html

2. LPOXY Therapeutics, Inc. acquires key assets from Xeno Biosciences Inc. to advance C difficile prevention therapy. News release. LPOXY Therapeutics Inc. January 4, 2024. Accessed September 4, 2024. 

https://firstwordpharma.com/story/5925021

The financing supports phase 3 evaluation of Sidiprev, a first-in-class, nonantibiotic therapy designed to prevent C difficile infections, a leading US health care–associated threat.

LPOXY Secures $28 Million to Launch Pivotal STOP-Cdiff Trial for C difficile Prevention

 infection (CDI), one of the most common health care–acquired infections, is associated with significant morbidity, mortality, and risk of recurrence. The Centers for Disease Control and Prevention classified CDI as an urgent threat in the 2019 antibiotic resistance threats report.

The 2022 update indicated a decrease in CDI cases in the years for which data were available, but the 2024 resistance threats report omitted CDI, so the trend in the past 5 years is not well-known.

 Recently, the CDI landscape has benefited from updated guidelines and approvals of 2 live biotherapeutic products, but there is still heterogeneity in the use and availability of various treatments.

CDI management requires knowledge of not only clinical trials and outcomes data but also formulary restrictions, product availability, and cost. As a result, treatment decisions made by excellent clinicians may sometimes be guideline discordant. An observational study published in 2024 compared fidaxomicin use before and after the 2021 focused guideline update from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America, which recommended fidaxomicin over oral vancomycin for initial and recurrent CDI.

 Although its use modestly increased, the authors concluded this agent was still underutilized and use varied by hospital location and size. A recent survey of infectious disease (ID) clinicians published in 

inquired further about CDI treatment preferences and barriers.

The survey was distributed to members of the IDSA Emerging Infections Network (EIN) via 3 separate emails in May 2024. The survey included physicians, pharmacists, and advanced practice providers practicing in adult IDs. The survey collected demographic information about respondents and the number of patients with CDI they had treated in the past year. Subsequent questions asked about usual practice, preferred treatment regardless of formulary or financial concerns, institutional guideline recommendations, and other situations. The results were analyzed using descriptive statistics.

Of the 1618 EIN members, 577 completed the survey, yielding a response rate of 36%. Nearly 90% were ID physicians, with the rest being other health care professionals. The practice settings of respondents varied, with the most common being university hospitals, nonuniversity teaching hospitals, and community hospitals. Those who responded had a significant amount of experience, with over 80% reporting at least 5 years of experience after terminal ID training and approximately 65% reporting treating over 10 patients with CDI in the past year.

Table

 infection; Ext, extended-pulsed fidaxomicin dosing regimen; IDSA, Infectious Diseases Society of America; PO, by mouth; PT, pulsed-tapered vancomycin dosing regimen; SHEA, Society for Healthcare Epidemiology of America; 10D, for 10 days.

describes some key survey findings alongside guideline recommendations. When asked about their institutional guidelines, 72% of respondents selected enteral vancomycin as first line for initial, nonfulminant CDI (but in some cases, local guidelines stratified choice of treatment by risk factors). Another question asked which patient characteristics influence clinicians to select fidaxomicin over other agents for nonfulminant CDI. Answers selected by over 50% of respondents were recurrent CDI, immunocompromised state, and age over 65 years. The most common barrier to prescribing fidaxomicin was outpatient insurance coverage issues (selected by 82%), followed by inpatient formulary or cost restrictions (47%).

The survey also inquired about alternative agents, including bezlotoxumab and fecal microbiota transplantation (FMT). Approximately three-quarters of respondents indicated having access to bezlotoxumab, a number which has likely decreased following the announcement of this drug’s discontinuation in early 2025.

 Just under 50% of respondents reported availability of FMT using donor stool in their practice, whereas 36% and 30% reported access to fecal microbiota, live-jslm (Rebyota) and fecal microbiota spores, live-brpk (Vowst), respectively. The COVID-19 pandemic, the US Food and Drug Administration’s changing policies around FMT, and high costs contribute to limited access to these therapeutics.

This study’s strengths include the large number of participants surveyed, the breadth of topics covered, and the focus on barriers that clinicians face in CDI management. Some limitations should be acknowledged, including sampling bias. Individuals with the most interest in CDI were possibly more likely to respond, and because the EIN subscribers did not include members of other relevant specialties, such as gastroenterology, these perspectives were not captured. This survey’s results reflect the time when it was distributed, prior to events in the past year that have affected access to specific therapeutics. The results highlight the challenges clinicians face while navigating financial approvals, inpatient and outpatient formulary restrictions, and product availability. Future cost-effectiveness studies and additional investigations into clinician perspectives, such as this one, can continue to help unite real-life practice and guidelines.

Antibiotic Resistance Threats in the United States, 2019

. Centers for Disease Control and Prevention. 2019. Updated December 2019. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/2019-ar-threats-report-508.pdf

COVID-19: US Impact on Antimicrobial Resistance, 2022 Special Report

. Centers for Disease Control and Prevention. 2022. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/covid19-impact-report-508.pdf

Antimicrobial Resistance Threats in the United States, 2021-2022

. Centers for Disease Control and Prevention. 2024. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/antimicrobial-resistance-threats-update-2022-508.pdf

4. Boton N, Patel PK, Beekmann SE, et al. Clinician management preferences for 

 infection in adults: a 2024 Emerging Infections Network survey. 

. 2025;12(7):ofaf335. doi:10.1093/ofid/ofaf335

5. Dubberke ER, Li Q, Obi EN, Turzhitsky V, Siddiqui F, Nathanson BH. A retrospective assessment of guideline adherence and treatment outcomes from 

 infection following the IDSA 2021 clinical guideline update: 

. 2024;11(10):ofae524. doi:10.1093/ofid/ofae524

6. Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of 

. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549

7. Kelly CR, Fischer M, Allegretti J, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. 

. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278

8. Drug shortages: bezlotoxumab injection. US Food and Drug Administration. December 23, 2024. Accessed July 19, 2025. https://dps.fda.gov/drugshortages/discontinuations/bezlotoxumab-injection

A recent publication describes the results of a clinician survey conducted in 2024 regarding preferences and actual practices in the management of C difficile infection in adults.

Clinical Corner 

Guideline vs Reality: Survey Results of Clinician Preferences in the Management of Clostridioides difficile Infection in Adults Highlight Barriers to Optimal Care

Aligning treatment with risk factors, patient profiles, and MBL status

When dealing with rising antimicrobial resistance, particularly the emergence of MBLs, a structured and coordinated response is critical. The identification of an MBL-producing organism should immediately trigger collaboration between microbiology, infection prevention, and clinical teams. Initial steps include confirming whether the patient has a true infection vs colonization and implementing strict containment protocols to limit the spread to other patients or hospital units. This level of resistance often means that standard empiric therapies are no longer effective, requiring more specialized interventions.

The type of MBL identified—such as New Delhi metallo-β-lactamases or other variants—can significantly influence treatment decisions. Unlike more common carbapenem-resistant organisms, MBL producers are susceptible to far fewer agents. Therapeutic options are limited and may include specific newer combinations, sometimes in dual-drug regimens, based on the resistance mechanism involved. Due to the complexity of matching drugs to resistance patterns, decision support tools like antimicrobial “stoplight” charts and susceptibility testing become vital. Even newer agents may face emerging resistance, so confirmation of activity through lab testing is essential before committing to a treatment course.

In critically ill or immunocompromised patients, especially those with recent broad-spectrum antibiotic exposure or prolonged hospitalizations, the threshold to escalate empiric therapy may be lower. However, the decision to use a novel agent still hinges primarily on risk factors such as prior culture data, regional resistance patterns, and exposure history rather than illness severity alone. This helps ensure the careful stewardship of last-line antibiotics, balancing the need for immediate effective therapy with the long-term goal of preserving these agents’ usefulness. Even in high-risk populations, empiric use of newer drugs is typically reserved for situations where there is strong evidence or history suggesting standard therapies will fail.

Panelists discuss the critical need for a coordinated, multidisciplinary approach to managing infections caused by metallo-β-lactamase (MBL)–producing organisms, emphasizing early identification, containment, careful selection of limited therapeutic options, and stewardship-guided use of novel agents to preserve their long-term effectiveness.

Guiding empirical therapy through patient risk assessment

In this segment, the discussion turns to practical strategies for selecting empiric antibiotic therapy amid growing multidrug resistance. The panel emphasizes that treatment decisions must balance clinical urgency with responsible antibiotic use. Clinicians are advised to first confirm whether a patient is truly infected or merely colonized, as unnecessary antibiotic use accelerates resistance. Patient history, such as recent hospitalizations, intensive care unit (ICU) stays, or exposure to long-term care facilities, also guides whether broad-spectrum agents are necessary. Local resistance patterns and antibiograms remain central tools for selecting empiric therapy, particularly when targeting organisms like 

The group acknowledges that in high-prevalence areas or in patients with known risk factors, standard empiric regimens like cefepime or meropenem may not provide sufficient coverage. In such cases, newer agents like ceftazidime-avibactam or cefiderocol may be considered empirically, though typically only in critically ill patients with strong indicators for resistant organisms. Rapid diagnostics and historical cultures are key to determining when to escalate empirically. However, there is consensus that these newer agents should not be used broadly for all patients, due to concerns over resistance development, cost, and limited access.

Institutions have taken a cautious approach to integrating these new antibiotics, often restricting their use through stewardship programs. At facilities like Johns Hopkins, advanced resistance screening—including rectal swabs for ICU and immunocompromised patients—helps identify colonized individuals who may benefit from more aggressive empiric therapy. Patients from regions with high resistance prevalence, such as South Asia or the Middle East, are also screened on admission. Ultimately, the panel agrees that the complexity of resistance mechanisms demands oversight from trained stewardship teams to ensure that novel agents are used appropriately and preserved for future effectiveness.

Panelists discuss practical strategies for empiric antibiotic selection in the face of rising multidrug resistance, stressing the importance of infection confirmation, patient risk assessment, local resistance data, and stewardship-guided use of newer agents to ensure appropriate and sustainable treatment decisions.

 released results from a new survey today that showed that 54% of the respondents were unaware and had no knowledge of 

The silver lining was that there was a 6% increase in awareness of the infection from just a few years before. A similar question was part of a survey conducted by Prodege in 2021, and 60% of respondents reported having no knowledge of

To read the survey's report, download the pdf at the bottom of this article, listed as "C Diff Awareness in America: 2025 YOUGOV Poll Results." 

“We’re encouraged by the steady growth in awareness we’re seeing,” said Christian John Lillis, executive director of the Peggy Lillis Foundation, in a statement. “Every percentage-point increase demonstrates the impact of our efforts to educate the American public about 

. Awareness is the first step to prevention, and these results show that our work and efforts are making a measurable difference.”

PLF, the nation’s leading nonprofit organization for 

education and advocacy, is releasing the results of its first nationwide survey to gauge public awareness of 

 infections. The poll was commissioned by PLF and conducted by YouGov, an international online research data and analytics technology group. One thousand respondents from the United States participated.

Of those who reported having knowledge of the infection, 19% of participants mentioned they learned about 

 through media coverage, including national health stories, public service campaigns, and patient advocacy initiatives. With PLF as the nationwide leader in 

 education and advocacy, this underscores PLF’s impact on the media landscape in the 7 years since it launched its "See 

The survey results also highlighted key gaps in public understanding. Despite increased familiarity, misconceptions about how 

 spreads and who is at risk remain widespread. A majority of respondents who were aware o

 still associated it exclusively with hospital settings, when in reality, recent data from the Centers for Disease Control and Prevention indicate that nearly half of

 infections originate in community settings, such as outpatient clinics and even households.



In response to these findings, PLF is using these data to shape new public awareness initiatives and strengthen its policy advocacy on behalf of patients and families affected by infectious diseases. By identifying where misconceptions persist, PLF can better equip communities with accurate and accessible information and push for stronger infection prevention policies and health care accountability nationwide.

"We view this poll not just as a snapshot of current awareness but as a road map for where we need to focus our efforts next," added Lillis. "From community education to legislative advocacy, these numbers will help us target the populations where increased knowledge can have the greatest impact."


Reference
New nationwide poll shows increase in C. difficile awareness through media coverage, highlights need for further outreach efforts. News release. Peggy Lillis Foundation. September 24, 2025. Accessed September 24, 2025. https://businessnewsthisweek.com/health/nationwide-poll-shows-rise-in-c-difficile-awareness-calls-for-more-outreach/

Although the number of people with knowledge about the infection rose, the results demonstrate a continued need for further education and awareness among the public. 

Yoav Golan, MD

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