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The globalization of antibiotic stewardship programs is necessary in the fight against antibiotic resis&shy;tance.

Globalization of Antibiotic Stewardship Programs: The World Is Waiting

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

Monica V. Mahoney PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, provides insights on the outpatient side of therapy and how the ever-changing approach to treating outpatients for gram-negative infections. 

Gram-Negative Infections and the Evolving Paradigm for OPAT

This is part of a short series looking at gram-negative infections, including diagnostics, treatment coordination, and newer agent uptake.

Outpatient parenteral antibiotic therapy (OPAT) refers to patients receiving intravenous (IV) antibiotic treatment outside of the hospital setting and can include patients’ homes, clinics, nursing facilities, or rehabilitation facilities. Typically, patients receiving OPAT are not being treated for severe gram-negative infections and are well enough to be discharged from the hospital. However, Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, clinical specialist at Beth Israel Deaconess Medical Center, who works in this space, is seeing a paradigm shift with more patients who do not have critical illness dealing with these infections. And with the introduction of new gram-negative agents, IV antibiotic infusion schedules can be highly irregular and questions around treatment stability become a front-and-center concern.

“There are logistical challenges with the infusion times of these newer medications in order to take advantage of their pharmacokinetic or pharmacodynamic properties. They're given over 2 hours or over 3 hours, so you're asking the patients to give that dose for that long amount of time. 'Oh, by the way, repeat it, and then 3 or 4 hours for your next dose,'” Mahoney said. “There are stability concerns. The drugs, once they're reconstituted in the form that's going to be infused in the patient, they are maybe good at room temperature for 4 hours in the refrigerator and for maybe up to 24 hours, if we're lucky. That doesn't work when the patient's at home…. The home infusion company will deliver the medications, ideally once per week. So we want longer stability data that you know you can keep this compounded medication in your refrigerator for the entire week.”

When considering OPAT with newer agents and thinking about stewardship, Mahoney says there are a number of factors to consider: “Is this going to be easy for the patient to take? Can we give a regimen that's simple enough for the patient or their family member to administer? If they won't take the medication because it's too complicated, they won't treat their infection. If they don't treat their infection, they're going to end up back in the hospital with the same cycle, possibly with a more resistant organism."

“While we still have the same core principles of stewardship in the outpatient setting, there are different priorities that we will place,” she said.

In terms of adoption of newer agents for gram-negative infections, Mahoney keeps the option open but acknowledges there are a few considerations, including the therapy’s availability, logistics, and coordination. 

“If the patient is well enough to go home, and if they have an organism that needs to be treated, we will investigate whatever we can to try to make it happen,” Mahoney said. “But it's a less contained environment. It is not our pharmacy. It is not our nurses; they are not within our institution. We need to coordinate with a lot of different people. We need to make sure that the home infusion company has it on their formulary. Sometimes they lag behind on adding these. If the patient's going to rehabilitation, we have to make sure that they will accept this patient with the level of complexity as well and that the appropriate follow-up and monitoring are in place to make sure that the patient is getting better.” 

“As a clinician, obviously I want to give the drug the patient needs, but sometimes the answer we come back to is, 'Unfortunately, we can't discharge you because you need to be on this medication, and the best place for you to be is in the hospital to finish out your course of therapy,'” she said.



Check out our next episode in the series when Ryan Shields, PharmD, MS, discusses new agents for gram-negative infections.

Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, provides insights on the outpatient side of therapy, including treating outpatients for gram-negative infections. 

Rodney E. Rohde, PhD, SV/SM/MB(ASCP)CM, FACSc, offers some insights on the latest diagnostics, susceptibility testing for newer antimicrobials, and how infectious disease clinicians and laboratory professionals can collaborate in case management to help challenging cases.

Adoption of Rapid Diagnostic Tools, Susceptibility Testing for Gram-Negative Infections

When thinking of diagnosing and treating gram-negative infections, there are some inherent challenges, including quick development of antimicrobial resistance, the time-consuming nature of traditional tests, and the limitations of rapid diagnostics in this area. And the unique cellular structure of gram-negative bacteria, which includes an additional outer membrane, can make antibiotic treatment more difficult.

One of the emerging areas within infectious disease is the development of diagnostic tools and how they are applicable to gram-negative infections. Some of these innovations include rapid diagnostics, next-generation sequencing, clustered regularly interspaced short palindromic repeats–based methods, utilizing artificial intelligence for data analysis and prediction, and the expansion of point-of-care testing, enabling faster, more accurate diagnoses.

Rodney E. Rohde, PhD, SV/SM/MB(ASCP)CM, FACSc, University Distinguished and Regents’ Professor and Chair for the Clinical Laboratory Science Program in the College of Health Professions at Texas State University, mentions a few of the rapid tests for identifying gram-negative bacteria, including the Biofire FilmArray for blood culture identification and the Cepheid GeneXpert, a platform to rapidly detect carbapenemase resistance genes. The Verigene Blood Culture Gram-Negative test is a rapid, microarray-based nucleic acid test that identifies common gram-negative bacteria and detects specific antibiotic resistance genes directly from positive blood culture results within hours. The BD MAX Enteric Bacterial Panel is a real-time polymerase chain reaction diagnostic test that identifies common enteric bacterial pathogens, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a rapid method for identifying microorganisms and other biomolecules by analyzing their unique protein "fingerprints." He notes the last one’s growth in hospitals and testing facilities.

“The MALDI-TOF, in general, as many of our audience will know, is becoming more and more implemented, especially in larger health care systems across the country, including Texas; it gives you a faster turnaround,” Rohde said. 

In terms of susceptibility testing for newer antimicrobials, Rohde says there are a lot of variables involved, including location, access to these tools, and the patient’s underlying comorbidities.

“There's a variety available to different microbiology laboratories, in which clinicians are ordering those tests…. You still might need to know as a clinician to interact with that microbiology laboratory team, the pharmacist, and others involved to pick the right susceptibility profile test.”

With the underlying challenges of identifying gram-negative infections and finding the right antimicrobials, Rohde stresses the importance of an all-hands-on-deck approach of building a team that includes providers, laboratory professionals, pharmacists, and everyone who touches patient care.

He believes everyone on these care teams should be pulling together, using their education and clinical experience for “collaborative communication.”

He stresses this to people in the field now, but he wants to see this approach taught in educational institutions, where they are training future professionals.

“That should be a part of the bread and butter of the education process now—no silos,” Rohde said. “We can’t operate like that anymore in the global world we live in.”



From Pathogen to Infectious Disease Diagnosis

.

Watch the next episode in the series when Monica Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, provides insights on the outpatient side of therapy.

References
1. Giacobbe D, Giani T, Bassetti M, Marchese A, Viscoli C, Rossolini G. Rapid microbiological tests for bloodstream infections due to multidrug resistant gram-negative bacteria: therapeutic implications. 


2. Anton-Vazquez V, Planche T. Gram-negative blood stream infections: prospects and challenges of rapid antimicrobial susceptibility testing. 


3. Why are gram negative bacteria harder to kill due to antibiotic resistance? Crestone. Accessed September 15, 2025. https://crestonepharma.com/why-are-gram-negative-bacteria-harder-to-kill-with-antibiotics
4. Ducret YV. Gram-negative bacteria: unveiling the complexity and resilience of a diverse group

. 2023;7(3):147.
5. Ciotti B, Nicolai E, Pieri M. Development and optimization of diagnostic assays for infectious diseases. 

. 2024;1(2):100032. doi:10.1016/j.lmd.2024.100032

Rodney E. Rohde, PhD, SV/SM/MB(ASCP)CM, FACSc, offers some insights on the latest diagnostics, susceptibility testing for newer antimicrobials, and how infectious disease clinicians and laboratory professionals can collaborate on challenging cases.

Adoption of Rapid Diagnostic Tools, Susceptibility Testing for Gram-Negative Infections 

Ryan Shields, PharmD, MS, discusses the challenges of incorporating new antibiotics for Gram-negative infections, how he is using broad-spectrum antimicrobial agents for these infections, and what are the factors he looks for in using new agents.  

Clinical Considerations on When to Use Newer Antibiotics for Gram-Negative Infections 

For the uninitiated, when new antibiotics are approved, it might be theorized that these therapies will become widely available and that providers will be able to add them to their armamentariums immediately. However, it is important to point out there is a lot more complexity to adopting new agents and there are careful considerations that need to be weighed before prescribing them, especially in the cases of challenging gram-negative infections.

Ryan Shields, PharmD, MS, associate professor of medicine and codirector of the Antibiotic Management Program at the University of Pittsburgh, says there are 3 main challenges around these prescribing scenarios and using newer agents for these types of infections.

“The first one is education. We've really made resistance and treating resistant gram-negative infections in particular quite challenging, and so it's really hard to keep up to date with the most recent evidence, particularly if you're not seeing these infections every day in your clinical practice. They're relatively infrequent, and so oftentimes you feel like you need to catch up. Now this is particularly true even across broad ranges of infectious diseases, but even outside of infectious diseases, keeping up with the latest mechanisms of resistance and new antibiotics that target those mechanisms of resistance, the education is a big lift that we all have to share in our clinical practice,” Shields said. “The second challenge we have is clinical evidence. Oftentimes, these new antibiotics get studied in patient populations that we don't ever really intend to use them in. A good example is maybe a regulatory trial that does a urinary tract infection study among generally healthy patients for a new antibiotic that we tend to use in critically ill patients with resistant bloodstream infections or respiratory tract infections. So there's a disconnect there that ultimately has to be filled with clinical experience and real-world data generation, and so until we have some of those additional data, it really is a challenge to know exactly how to use a new antibiotic. The third challenge that I think we all face in this current climate of health care is the added emphasis that's on cost. In particular, around cost containment, the new antibiotics are severalfold more expensive than some of the traditional agents we've been using, and so as stewardship teams and infectious diseases clinicians, we have to justify the added cost of the new antibiotic in terms of what we think it can benefit for patients.”

These challenges inform how Shields prescribes. In terms of data, he wants to see positive results from studies that examine the intended pathogens in the intended patient populations.

“A recent example of this that speaks to those notes is sulbactam durlobactam. There was a clinical study among patients with the intended pathogen—in this case, carbapenem-resistant 

, and in the intended patient population, those with pneumonia and bloodstream infections,” Shields said. “So even though it was a smaller study, it gave us as clinicians some confidence to say this is a new antibiotic that worked well for the pathogen of interest in the patient population of interest. Now there's more nuance for that. Each of these pathogens has its own challenges and diverse resistance mechanisms, but probably the other way in which we start to favor antibiotics is when we have comparative data, particularly comparative effectiveness data.”


This concludes this series. Look for the other interviews within the sidebar above. 

Ryan Shields, PharmD, MS, discusses the challenges of incorporating newer antibiotics for gram-negative infections, how he is using broad-spectrum antimicrobial agents for these infections, and the factors he looks for in considering new agents.  

Clinical Considerations for Using Newer Antibiotics for Gram-Negative Infections 

MeMed CEO Eran Eden, PhD, discusses the MeMed BV test and how it can help make the distinction between the types of infections, 

From Pathogen to Infectious Disease Diagnosis: 

One of the ongoing treatment challenges for providers is the ability to determine whether infections are bacterial or viral. Their presentation can be similar, and traditional testing can be time-consuming. Of course, clinicians want to be sure patients are receiving some type of intervention, so broad-spectrum antibiotics can often be prescribed in these cases.

“It [the MeMed BV test] tries to solve the following seemingly simple problem: A patient, a kid or adult, comes to urgent care or to an ED [emergency department] with a suspected acute infection. Broadly, we're trying to discern the etiologies of a bacterial or viral infection. Do we treat or not treat with antibiotics?” said MeMed's cofounder and CEO, Eran Eden, PhD.

Eden’s company developed a novel assay, the MeMed BV test, that can distinguish between bacterial and viral infections in 15 minutes. The test received a US Food and Drug Administration 510(k) clearance in 2023 and also has the European CE mark.



Eden says the test itself is a blood test that measures 3 proteins and integrates them into a score. “They are measured and then computationally integrated into a score between 0 and 100; the higher the score, the higher the likelihood of a bacterial infection.” 

MeMed shared results of 3 studies of the MeMed BV test, which demonstrated the following:

63% reduction in unnecessary antibiotic prescriptions (real-world study of 3920 patients)

70% of previously missed bacterial infections correctly identified, leading to significantly fewer hospitalizations (7.8% vs 30.3%)

Outperformance of standard biomarkers such as procalcitonin in distinguishing bacterial vs viral infections

Lower health care costs, especially in managing community-acquired pneumonia


Eden mentions the multiple challenges of pathogen testing. “The first is that even if you use a multiplex PCR [polymerase chain reaction], you're only going to put your hands on a microorganism in 30 to 40% of the cases; [in] 60% of the cases, there is no microorganism, and you still have to treat, so that's one gap we're trying to solve,” Eden said. “The second thing is inaccessible infections. So you can apply, say, a SARS-CoV-2 or strep [

test in cases of pharyngitis. But what about otitis, bronchitis, and pneumonia? The immune system circulates throughout the entire body, so it allows you to identify these infections or the source of infection in these inaccessible infection sites. Third is the issue of colonization. So let's say you identify a virus or bacteria. Some of them have very high prevalence, especially in kids, so mere detection does not apply causality, which is confusing, leading to overuse and underuse of antibiotics. Another element here is the element of superinfections. So you identify an influenza. There's about 10% to 20% probability of bacterial superinfection on top of that. So all these elements and obviously time—you want to get results fast—it's taking this simple problem and making it really hard to discern in real time.” 

He says these factors lead to uncertainty about the nature of the infection and that they are trying to reduce that with the use of this newer generation of screening tools. He says screening can greatly aid in antibiotic stewardship and address the global issue of antimicrobial resistance.

“When you talk about reduction of overuse, I would like to maybe broaden the discussion to say it's both…depending on the overprescribed or nonbacterial infection for which it does not provide any benefit,” Eden said. “But there's also an element of underuse where you should prescribe and you're not prescribing…. The BV test has started to show utility in reducing this uncertainty, reducing overuse of antibiotics but at the same time doing it in a safe manner [and] also reducing cases where there are missed bacterial infections.”



References
1. MeMed BV test demonstrates antibiotic overuse reduction in first US interventional trial. News release. 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. MeMed BV proven to optimize antibiotic use, outperform standard care, and cut costs in new studies. News release. MeMed. February 27, 2025. Accessed April 11, 2025.
https://www.me-med.com/press_release/memed-bv-proven-to-optimize-antibiotic-use-outperform-standard-care-and-cut-costs-in-new-studies/



MeMed CEO Eran Eden, PhD, discusses the MeMed BV test and how it can help make the distinction between the types of infections, aid in patient management, and reduce antimicrobial resistance.

From Pathogen to Infectious Disease Diagnosis: Test Determines Between Bacterial and Viral Infections in 15 Minutes

In our latest From Pathogen to Infectious Disease Diagnosis podcast, bioMérieux Chief Medical Officer Chuck Cooper, MD, discusses the burden of resistance, and insights on the company’s novel Vitek Compact Pro ID/AST system.

Can Diagnostics Aid in Alleviating Antimicrobial Resistance and Sepsis? 

Antimicrobial resistance (AMR) continues to be an increasingly significant public health issue, leading to higher mortality rates. Findings from one study estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths.

Untreated or undertreated bacterial infections are a major cause of sepsis, a serious complication that places a significant burden on hospitalized patients. The Centers for Disease Control and Prevention estimates that 1.7 million adults in the US develop sepsis each year. In terms of mortality, the agency reports that at least 350,000 adults who develop sepsis die during hospitalization or are discharged to hospice. Additionally, 1 in 3 people who die in the hospital had sepsis.

Chuck Cooper, MD, chief medical officer at bioMérieux, highlights the urgency of timely diagnosis and treatment.

“Every hour of delay in getting patients on effective therapy dramatically increases their mortality,” Cooper said.

“The challenge with antimicrobial resistance is that it compromises our ability to treat sepsis effectively, because it limits the options from an antimicrobial therapeutic perspective and it makes it more difficult to get patients on the right therapy as quickly as possible,” Cooper said. “So it's critically important for clinicians to receive accurate, rapid information about the antimicrobials that will work for an infection so that they can treat patients with the effective therapy as soon as possible.”

To address resistance—and by extension, sepsis—bioMérieux has developed a diagnostic platform designed to efficiently and quickly identify infectious diseases. Earlier this year, the US Food and Drug Administration cleared bioMérieux’s Vitek Compact Pro ID/AST system for microorganism identification (ID) and antibiotic susceptibility testing (AST). This system is intended to support clinical laboratories in identifying infectious diseases and combating AMR and for use in industrial laboratories to identify contaminants and ensure consumer safety.

“The Vitek Compact Pro provides both microorganism identification and antibiotic susceptibility testing results. This is essential for helping laboratories diagnose infectious diseases and combat resistance,” Cooper said.

The Vitek Compact Pro ID/AST system combines new diagnostic technology with features from its predecessor, the Vitek 2 Compact. With an ergonomically advanced design and simplified workflow, it enhances the user experience and boosts efficiency, reducing the time laboratory technicians need to spend on sample loading and processing.

“It has a very intuitive user interface with guided workflow steps. This leads to a faster, more streamlined hands-on process before loading cassettes into the instrument, significantly reducing hands-on time,” Cooper added.

For industrial applications, the system will be used for the routine identification of pathogens to help ensure the quality and safety of food, pharmaceutical, and cosmetic products.

The commercial launch of the Vitek Compact Pro is planned in select countries, with a global rollout beginning this quarter.

1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. 

. 2022;399(10325):629-655.
2. About sepsis. Centers for Disease Control and Prevention. March 8, 2024. Accessed May 16, 2025. https://www.cdc.gov/sepsis/about/index.html
3. bioMérieux receives FDA 510(k) clearance for its Vitek Compact Pro, a new ID/AST system to fight against antimicrobial resistance. Press release. bioMérieux. March 18, 2025. Accessed May 16, 2025. 

https://www.biomerieux.com/corp/en/journalists/press-releases/vitek-compact-pro-fda-clearance-antimicrobial-resistance.html

In our latest From Pathogen to Infectious Disease Diagnosis podcast, bioMérieux Chief Medical Officer Chuck Cooper, MD, discusses the burden of resistance and insights on the company’s novel Vitek Compact Pro ID/AST system, which looks to identify infectious disease in a timely manner and aid clinicians in diagnosing patients, streamlining antimicrobial treatment, and avoiding severe complications such as sepsis. 

ANGELIKI MESSINA, MSPHARM, BSPHARM

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