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As antimicrobial therapies become less effective, more people are at risk for infections that can progress to sepsis.

Sepsis and Antimicrobial Resistance Awareness Gain Ground, But Action Must Continue

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 benefits, challenges, and prospects of wastewater data in enhancing public health strategies against AMR.

Transformative Potential of Wastewater Surveillance in Monitoring Antimicrobial Resistance

Valerie Morley, PhD, senior scientist at Ginkgo Bioworks, recently delivered a presentation at the World AMR Congress on the role of wastewater surveillance in monitoring antimicrobial resistance (AMR) across diverse environments, including healthcare settings and agricultural sites. Her talk focused on drawing valuable public health insights from wastewater surveillance for AMR.

She highlighted the benefits of wastewater surveillance for obtaining population-level data, which complements cultured clinical isolates.“Wastewater surveillance is a cost-effective way to get population-level data that can be very targeted. We can look at wastewater coming from a single ward or unit in a hospital, or it can be very broad. We can look at municipal-level wastewater that's coming from an entire community, and importantly, wastewater allows us to get data from the community setting as well as healthcare settings.”

Morley identified technical challenges in associating resistance genes with bacterial organisms and the complexity of interpreting metagenomic data. “One of the big examples that comes to mind for me is that with metagenomic data, we often can't make associations between the resistance genes that we're detecting and the bacterial organisms that they're associated with.”

Morley noted that these challenges stem from limitations in current sequencing approaches but highlighted ongoing efforts to improve accuracy through new methodologies. “That's just kind of a limitation of most types of sequencing approaches, and that's a place where, if we can start to make those associations more accurately, that's really valuable. We're working on that both, there's new approaches coming out that help us to do that. On the wet lab side, they're expensive right now compared to other sequencing methods, and there's also ways to potentially get better at doing that bioinformatically and from a statistical perspective, to make those predictions.”

She underscored the importance of collaborating with end-users to extract meaningful insights and discussed the potential of wastewater surveillance to inform public health strategies. This includes reducing healthcare-associated infections and guiding antimicrobial stewardship through large-scale pilots and data correlation with electronic health records.

“We're really excited about the idea that wastewater surveillance could help hospitals to reduce healthcare-associated infections and to make decisions regarding antimicrobial stewardship. ... This could help to inform when hospitals might want to turn on heightened infection control procedures or more targeted surveillance methods like sequencing or testing swabs, for example.”

In conclusion, Morley highlights wastewater surveillance as a promising tool for monitoring AMR in both healthcare and community settings. While this approach provides valuable population-level data that complements traditional methods, it faces challenges in data interpretation and accuracy. Advances in technology and data integration are expected to enhance its effectiveness, potentially improving infection control and antimicrobial stewardship.

World Anti-Microbial Resistance Congress

Conferences

In a world that has become skeptical of vaccine safety and efficacy, a new modeling study from England demonstrates the continued high efficacy of the MMR vaccine. According to a new study published in 

, the MMR vaccine remains highly protective against measles for life, and sees a very small decrease in protection over time.

According to the investigators, for a person who was born in 1995 who received a full immunization (2 doses) of the MMR vaccine before age of 5 and gained full protection from the vaccine, a waning of about 0.04% each year would mean vaccine effectiveness remains on average:

A Small Uptick in Measles Cases Among Fully Vaccinated

In England in 2011, 20 individuals who were double-vaccinated were infected with measles (1.9% of all cases) compared to 989 unvaccinated people (93% of all cases). In the same country in 2019, 57 individuals vaccinated twice had measles (7.2% of all cases) compared to 666 unvaccinated people (84% of all cases). This shows a slight uptick in cases in the fully vaccinated, but the investigators write that the slight decreases in individual protection over time are only apparent because outbreaks are happening as a result of reductions in vaccine coverage, and highlight that the best way to protect everyone from the disease is to maintain high levels of vaccine coverage in the population

“Although our results suggest that a slight waning of immunity from the MMR vaccine over time explains why we are seeing an increase in the proportion of measles cases in double-vaccinated people in England, it’s important to note that the biggest risk factor for measles outbreaks by far is low vaccination rates,” study investigator Alexis Robert, PhD, The London School of Hygiene & Tropical Medicine, said in a statement. “The MMR vaccine remains highly effective and receiving two doses will protect you and those around you against measles infection. Even if you are one of the small number of people who get an infection after two doses of MMR vaccine, previous studies suggest measles symptoms in people who have been vaccinated are milder than in people who have not had a vaccine.”



More than 95% of individuals gain immunity after a single dose of MMR vaccine. This means that after 2 doses, a small proportion of vaccinated people (less than 1%) may be infected because of a lack of immune response.

Transmissibility and The Seriousness of Missing Childhood Immunizations


Measles is spread by breathing in contaminated air or touching an infected surface then touching the eyes, noses, or mouths. According to the Centers for Disease Control and Prevention (CDC), the measles virus can live up to 2 hours in airspace after an infected person leaves an area and can linger on surfaces for hours. And, if you put a person with measles in a room with 10 people who have not been vaccinated or have not previously contracted measles, 9 of those people will also get the disease.

“Measles is the most contagious and easily transmittable virus we know—far more than COVID or influenza,” said Patricia A. Stinchfield, RN, MS, CPNP, president, National Foundation for Infectious Diseases (NFID) in an interview with 

Considered one of the most successful immunizations, the MMR vaccine has done much for public health for years. However, there has been a continuing downward trend of childhood immunizations here in the United States.

 that over the last 2 school years, the national coverage for childhood state-required vaccines among kindergarten students declined from 95% to approximately 93%. During the 2020-21 school year, vaccinations dropped to 94% and during the 2021-22 school year it dropped again to approximately 93%.

And while this does not sound like a large number, it still represents thousands of young children not getting their vaccinations. It is also a disturbing trend as some families may feel they do not need them or are fearful of vaccines.

“Compared with the 2020–21 school year, vaccination coverage decreased 0.4–0.9 percentage points for all vaccines. Although 2.6% of kindergartners had an exemption for at least 1 vaccine, an additional 3.9% who did not have an exemption were not up to date with MMR,” the investigators wrote in an 

This is the lowest rate of vaccination in over a decade, the CDC states. And the MMWR report said that as many as 250,000 kindergartners are not protected against measles.

The reduction in the number of fully vaccinated children can only lead to more cases. In local communities this can present a real problem explains, NFID's Stinchfield.

“When those rates go below 95%—and this is really about in a specific community, what is the rate in the daycare? What is the rate in a high school? In a city? In a state?” Stinchfield explained. “To just take a big global number and say that's pretty high, we're good, is not okay. When a local community gets below 95%, that gives measles an ability to make an entrance and spread in that community.”

She also makes the point that there are people who are vulnerable to measles including babies who are too young to be immunized, those who are immunocompromised, and people who are on various therapies that might make them more susceptible to the disease.



This should give families who are reluctant to get childhood immunizations something to consider in thinking about others.

1.Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study. Lancet Public Health. September 26, 2024. Accessed September 26, 2024.


https://www.thelancet.com/journals/lanpub/article/PIISS2468-2667(24)00181-6/fulltext


2.Measles. Transmission. CDC. Last reviewed November 5, 2020. Accessed September 26, 2024.


https://www.cdc.gov/measles/transmission.html


3. Parkinson J. Measles Outbreak in Philadelphia Prompts Caution, Calls for MMR Vaccination. 

 January 8, 2024. Accessed September 26, 2024.


https://www.contagionlive.com/view/measles-outbreak-in-philadelphia-prompts-caution-calls-for-mmr-vaccination


4. Parkinson J. A Comprehensive Look at Measles. 

March 13, 2024. Accessed September 26, 2024.
https://www.contagionlive.com/view/a-comprehensive-look-at-measles

An English modeling study suggests level of protection decreases only very slightly over time and reminds parents to have their children up to date on all vaccinations.

Though MMR Vaccine Remains Highly Protective Against Measles, Some Waning Immunity Can Lead to Outlier Cases 

One of the ongoing challenges for clinicians is determining if infections are either bacterial or viral. Their presentation can be similar, and testing to determine if infections are the former or the latter can be time consuming. Clinicians want to make sure their patients are getting some type of intervention, so broad-spectrum antibiotics can often be prescribed in these cases.

A novel assay, the MeMed BV test, can distinguish between bacterial and viral infections in 15 minutes. The test received a FDA 510(k) clearance last year and also has the European CE Mark.

A new study, the JUNO trial, was conducted by the manufacturer and demonstrated a 62% relative reduction in unnecessary antibiotic prescription rates—33% in the control group versus 13% in the MeMed BV (MMBV) group (p=0.003). Importantly, follow-up data indicated no significant increase in the rate of return emergency departments (EDs) and urgent care centers (UCCs) visits within 7 days, with 4.7% in the control group compared to 3.8% in the MeMed BV group. The data was presented at the ongoing ACEP24 Scientific Assembly by Adam Singer, MD, vice chairman for Research and Professor, Department of Emergency Medicine, Renaissance School of Medicine, Stony Brook University, New York.

The JUNO trial is a randomized controlled trial conducted across 11 EDs and UCCs in the US and Israel. It enrolled 260 adult patients with clinical suspicion of lower respiratory tract infection (LRTI). The first small-scale analysis of data from the trial, which focused on a subgroup of 160 patients.

“These preliminary results underscore the potential of MeMed BV to significantly influence antibiotic stewardship, reducing unwarranted antibiotic prescriptions while enhancing patient outcomes. We are now recruiting for a larger randomized controlled trial, which will further solidify the clinical value of the test," Singer said in a statement.

These infections are particularly challenging for clinicians especially as antimicrobial resistance continues to be an ongoing issue. Patients in some treatment environments, such as long-term care settings, may be delayed in getting diagnosed, and often patients can be given broad-spectrum antibiotics that may be limited in efficacy and leads to switching antibiotics and more exposure to these therapies and the possibility of antimicrobial resistance (AMR). One of the more important, emerging concepts is the Time-to-Treat paradigm, which is essential to getting patients antimicrobials with susceptibility to infections in an efficient time span.

Addressing gram-negative antimicrobial resistant infections has been a significant issue, and the Infectious Diseases Society of America (IDSA) decided to update treatment guidance this year. Back in August, the organization 

 for managing antimicrobial resistant infections, including those caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), difficult-to-treat 

 (DTR P. aeruginosa), carbapenem-resistant 

The MeMed BV test's manufacturer, Haifa Israel-based, MeMed, is planning to continue with studies. "The results of this trial build on a decade-long series of studies involving thousands of patients, demonstrating the high performance of the MeMed BV technology,” MeMed's co-founder and CEO Dr. Eran Eden, said in a statement. “This trial marks a significant step forward by generating interventional data and showcasing the test's actual impact on patients. We are committed to further expanding on these findings, with several additional utility and real-world studies underway. We are deeply grateful to Diasorin and BARDA for supporting this trial and for advancing the host-response field."

1.MeMed BV Test Demonstrates Antibiotic Overuse Reduction in First US Interventional Trial. MeMed. September 30, 2024. Accessed September 30, 2024. 

https://www.prnewswire.com/news-releases/memed-bv-test-demonstrates-antibiotic-overuse-reduction-in-first-us-interventional-trial-302260001.html

2. Infectious Diseases Society of America. IDSA 2024 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Published Clinical Infectious Diseases July 12, 2024. Accessed August 7, 2024. 

https://www.idsociety.org/practice-guideline/amr-guidance/

A novel test is looking to ascertain this diagnostic information quickly to aid clinicians in making a determination of infections and more efficiently prescribe antimicrobials.   

Determining If the Patient’s Infection is Bacterial or Viral

Maryann Webb’s harrowing personal experience with C diff, along with her professional work with federal government agencies has prepared her for a life in advocacy with the Peggy Lillis Foundation

Advocating for Better Regulatory Rules and Standard of Care for C difficile

Make no mistake; Maryann Webb is a fighter. She has battled both 

 and breast cancer simultaneously. During her sickest time, she felt her organs shutting down, and she was getting her affairs in order because she thought she was going to die.

“I was just wasting away. I could feel myself dying…I really just didn't know what was going on, but I knew that I was nearing the end of my life, so I carefully, without anyone noticing, I got rid of a lot of my possessions, so that my daughter and my husband wouldn't have to deal with that,” Webb said.

In the midst of her severe infection, she also developed breast cancer and needed a double mastectomy.

 continued on. She was dealing with the infection between 2015 and 2018, and finally, after suffering for 3 years, she got some help from her family. “At the very last minute, my sister-in-law put me in touch with a doctor who did fecal microbiota transplants (FMT)…And when I did receive the FMT, about 8 hours after it, I knew that the infection was gone and from that moment on, I just got better,” Webb said.

After her health transformation, Webb began getting involved in advocacy in 2019 including working with the 

 She is now a member of the PLF's Board of Directors, and will be presented with the Advocate Award at the organization's 15th Annual Changing the Odds Gala this November.

 inspired her to get involved and help others suffering from the infection. “I'm extremely honored. The reason that I do this advocacy work is I know what it's like as a survivor to have suffered through this infection,” Webb said. “I know how isolating and dehumanizing it is, and I know the stigma that's attached to it. I understand the pain and the hopelessness that people feel when they're going through this. So, once I recovered, it just seemed incumbent upon me to be able to reach out to the people who are still in that bed and offer them the hope that I didn't have, and the support that I didn't have, and try to create that kind of community for them.”

It is this last part she feels has not been recognized and people suffering from the infection need support.

“If you know someone who has C diff, please offer them any kind of support and assistance that you can and also encourage them to get some mental health as part of their treatment, because it's a very, very trying, isolating disease,” Webb said.

As part of her advocacy, she would like to see FMTs become more accessible. After years of suffering, she was able to get the procedure.

“I went to see this doctor, and he said, ‘I'll do an FMT for you right away’. Without getting into any of the tedious details of insurance, it was a little bit of a battle,” Webb said. “There is a system put into place for step therapy, which requires you to have failed treatments before you can have access to the FMT under emergency use authorization. So unfortunately, that's something that I would like to see change, because it requires a lot of pain and suffering unnecessarily.”

Another area she and PLF is involved in is trying to get the federal legislation, the Peggy Lillis 

 Inclusion Act, passed. Back in July, congresswoman Yvette Clark (D-NY) introduced this bill into the House of Representatives, which calls for 

 to be recognized as a nationally notifiable infectious disease and condition.

This bill is named in honor of Peggy Lillis, who was a single mother and kindergarten teacher in Brooklyn, New York who lost her life to a 

infection. Her son, Christian, and his brother, Liam, cofounded the foundation in the summer of 2010, following the death of their mother from a community-acquired 

, their mother was a healthy 56-year-old kindergarten teacher. She was only sick for 6 days before succumbing to the infection.

For the general public, Webb would like people to realize the seriousness of the infection. “

 is antibiotic resistant superbug, and we feel that the cornerstone of being able to develop any kind of treatment and awareness around this disease.”



Reference
1.Clarke Introduces Legislation to Prioritize Research on C. Infections. July 25, 2024. Accessed July 30, 2024.


https://clarke.house.gov/clarke-introduces-legislation-to-prioritize-research-on-c-diff-infections

Maryann Webb’s harrowing, personal experience with C diff, along with her professional work with federal agencies has prepared her for a life in advocacy with the Peggy Lillis Foundation. She wants to see the fecal microbiota transplant become more accessible and is working with Congress to make the infection a notifiable infectious disease.

Continuous antibiotic infusions show positive results and may improve outcomes for patients with severe sepsis.

Sepsis Awareness Month: Highlighting the Findings from BLINGIII

In a study that could reshape sepsis management practices worldwide, the B-Lactam Antibiotic Infusion Trial (

) has yielded findings that challenge existing protocols. Led by Jeffrey Lipman, MD, DMed(Res), an intensive care specialist and principal investigator of the trial, the research involved 7,200 patients and compared continuous versus intermittent infusions of b-lactam antibiotics.

While the primary analysis indicated no significant reduction in 90-day mortality between the two infusion methods, Lipman highlighted a key takeaway: “The primary analysis showed a 1.9% reduction, which did cross the unity line. Therefore, the conclusion may have been a bit negative, but if you read the data, the trial showed a significant improvement in outcomes compared to previous studies.”

The trial's findings are underscored by a systemic review of 18 trials encompassing 9,000 patients, which demonstrated that continuous infusions could improve mortality rates, requiring the treatment of 26 patients to save one life. Lipman emphasized the necessity of continuous infusions for patients with severe sepsis, predicting a global shift in sepsis management, “There will be changes throughout the world over time, and it will save thousands of lives.”

This conversation coincides with Sepsis Awareness Month, prompting critical conversations in intensive care units. Lipman posed a crucial question: “Is it only severe sepsis that needs continuous infusion, or should all patients with sepsis and some organ dysfunction have a continuous infusion introduced?” This inquiry could pave the way for broader adoption of continuous infusion practices in treating sepsis.

Lipman noted the slow but inevitable evolution of medical practice, stating, “I think there will be a change. It takes time for medical practice to change, but in previous guidelines, there was weak evidence that continuous infusions were beneficial. Now there is strong evidence.” He believes this evidence will lead to improvements in the lives of countless patients globally.

Additionally, Lipman addressed the complexities surrounding antibiotic administration in sepsis management. He pointed out that the current practice is often risk-averse, leading to unnecessary antibiotic use in patients who may not have a confirmed infection. “There will be changes over time in the diagnosis of sepsis, more definitively in the ICU, so that the appropriate antibiotics can be given only to those patients with sepsis,” he said.

He also challenged traditional beliefs regarding the duration of antibiotic courses, noting, “The long courses of antibiotics... are being challenged, and there will be shorter courses of antibiotics used worldwide.” This shift aims to mitigate antibiotic misuse and the subsequent rise of resistant organisms.

As the medical community explores new markers for sepsis, many of which are currently under investigation, Lipman remains hopeful about the future of sepsis treatment. “A better marker for sepsis is being investigated in many places, with some promising responses, but still, there isn't a good marker for a lot of patients with sepsis in the ICU,” he remarked.

The findings from the BLINGIII trial not only contribute to the ongoing discourse around sepsis management but also signal a potential turning point in how healthcare professionals approach this critical condition. With a focus on continuous infusion and more precise antibiotic use, there is optimism for improved patient outcomes in the face of sepsis.

Konrad Reinhart, MD

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