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Farm to Table: How Antibiotic Use in Agriculture Affects Human Health

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

A recent study comparing ceftolozane/tazobactam and ceftazidime/avibactam for difficult-to-treat Pseudomonas aeruginosa infections found no statistically significant difference in resistance emergence—but a surprising numerical trend favoring ceftazidime/avibactam. Pranita Tamma, MD, MHS, continues her conversation around this topic.

Statistical Weighting Method Helps Reduce Bias in Observational Study

In this short series with Pranita Tamma, MD, MHS, associate professor of pediatrics in the Division of Pediatric Infectious Diseases at The Johns Hopkins University School of Medicine, she has a discussion about ceftolozane-tazobactam vs ceftazidime-avibactam for gram-negative resistant 

 infections and the latest data supporting these decisions.

In one retrospective observational study, which compared ceftolozane-tazobactam and ceftazidime-avibactam and was funded by the National Institutes of Health, the findings showed similar 30-day mortality rates but higher resistance emergence in the ceftolozane-tazobactam group (38% vs 25%). Tamma was the senior investigator in this trial.

Below is a response from a conversation with her about this trial.



How did the use of inverse probability weighting and propensity scores strengthen the validity of the study’s findings?

Because the study we conducted is observational, there will always be some bias we can’t control. In an ideal world, we’d run a randomized clinical trial, where patients have an equal likelihood of receiving ceftolozane-tazobactam or ceftazidime-avibactam. With observational studies, we do our best: We collect data on severity of illness, age, comorbidities, source of infection, and other factors, and we try to balance these variables as much as possible.

In the end, we’re left with 2 groups of patients who are similar in all measurable characteristics that could affect clinical outcomes, except for the drug they received. There are several ways to achieve this balance in observational studies, though none is as rigorous as a clinical trial.

One approach is traditional logistic regression. Another is matching patients on key variables, though you can never match on everything, which is a limitation. A third is propensity score analysis, which adjusts for variables that might influence the choice of one drug over another.

In our study, we used a specific method called inverse probability of weighting with a propensity score. The propensity score represents the probability—based on variables like age, severity of illness, or transplant status—that a patient would receive one drug vs the other.

Here’s an example: imagine a study of gram-negative bloodstream infections comparing 7-day vs 14-day antibiotic courses. In an observational setting, patients receiving the longer course are often sicker—perhaps with a complex infection source or immunocompromise—while the shorter-course group tends to be healthier. That’s bias.

Propensity score weighting helps adjust for this. For instance, if I were 75 years old, had a liver transplant, was in the ICU [intensive care unit] on vasopressors, and received only 7 days of therapy, I’d be overrepresented in the short-course group. The software would weight me more heavily—maybe counting me as 2.5 patients—because my profile is rare in that group. Conversely, in the prolonged-course group, where many patients look like me, I might count as only half a patient.

By using inverse probability weighting with propensity scores, we aim to make the 2 groups more comparable so the main difference between them is the treatment they received. Of course, residual confounding and limitations always remain, no matter the method, but we felt this was the best approach to reduce bias in drug selection.


The conversation was edited for grammar and clarity.

Pranita Tamma, MD, MHS, continues her conversation about a study she was involved in that compared ceftolozane-tazobactam and ceftazidime-avibactam. She discusses the usage of inverse probability weighting with propensity scores to balance patient groups and limit bias. 

Statistical Weighting Helps Reduce Bias in Observational Studies

Determining Resistance Patterns in Difficult-to-Treat Resistant Pseudomonas Infections

Below are responses from a conversation with her about this trial as well as other data on this topic.



: Resistance emergence was higher in the ceftolozane-tazobactam group, though not statistically significant. How should clinicians interpret this trend when selecting therapy?

Yeah, so the resistance outcome was interesting. As you know, we didn’t see a statistically significant difference in the emergence of resistance. There was a numerical difference that stood out, though. I don’t want to misquote the numbers, but I believe resistance emerged in 38% of the ceftolozane-tazobactam group and 25% in the ceftazidime-avibactam group. Again, not statistically significant, but still notable.

In my opinion, our study doesn’t provide enough data to draw firm conclusions. But what I appreciated—and I want to highlight that Dariusz Hareza is the first author—is that we had access to both the index 

 isolates and subsequent isolates, which allowed us to perform broth microdilution testing for MICs [minimum inhibitory concentrations]. That’s the reference standard, and this kind of detailed susceptibility testing wasn’t done in the other 2 studies. In those, isolates were either unavailable or not tested with broth microdilution.

That’s not a criticism of those studies—they’re still good—but I do think it’s important. If we’re comparing 2 drugs for resistance or clinical outcomes, it’s essential to know whether the isolates were susceptible to the drugs being studied. Otherwise, the foundation of the study is shaky. We don’t even know if the treatments were active up front.

Using broth microdilution, we were able to look for emergence of resistance. Still, our sample size was small, so I don’t think we can draw meaningful conclusions from it. Personally, I tend to prefer using ceftolozane-tazobactam over ceftazidime-avibactam for DTR

, just because ceftolozane-tazobactam is more focused on 

. I typically reserve ceftazidime-avibactam for carbapenem-resistant Enterobacterales, like KPC [

 carbapenemase] producers and OXA-48–like producers. So despite the findings from our study and the 2 other observational studies, I don’t think there's enough evidence to favor one drug over the other based on mortality or resistance alone.

From an antibiotic stewardship perspective, I still lean toward starting with ceftolozane-tazobactam, assuming both drugs are active against the 

, simply because I want to preserve ceftazidime-avibactam for other resistant infections that these patients might develop.

Sorry for the long response, but speaking more generally about resistance, it’s important to note that ceftolozane, as a β-lactam, is engineered to be more active against 

 than ceftazidime. It’s less prone to efflux and porin channel issues, both of which limit β-lactam entry into the bacterial cell. It also has higher affinity for PBP3, its target, and is more stable against hydrolysis by the 

So, as a molecule, ceftolozane is clearly superior to ceftazidime. What ceftazidime gains, though, is avibactam, which inhibits AmpC and allows ceftazidime to reach its target. Mechanistically, I would have expected ceftolozane-tazobactam to be less likely to lead to resistance than ceftazidime-avibactam.

But we were surprised in our study: Numerically, resistance seemed more frequent with ceftolozane-tazobactam. One hypothesis for this is that both drugs share a common resistance mechanism—amino acid changes in the 

 AmpC enzyme. These mutations make the enzyme’s active site more flexible and better able to hydrolyze β-lactams like ceftolozane or ceftazidime. It’s possible that avibactam—as a more potent β-lactamase inhibitor—can still bind to some of these nonmutated enzymes and protect ceftazidime, whereas tazobactam may not effectively inhibit these mutated AmpC enzymes.

So going into the study, I would’ve guessed ceftolozane-tazobactam would have a lower resistance rate. We were surprised. But again, the numbers are small, and the other 2 studies didn’t assess resistance emergence in a robust way because they lacked MIC data from reference methods.

So, in my view, this remains an open question and one that deserves further investigation.

The conversation was edited for grammar and clarity.

Results from a recent study comparing ceftolozane-tazobactam and ceftazidime-avibactam for difficult-to-treat Pseudomonas aeruginosa infections found no statistically significant difference in resistance emergence but a surprising numerical trend favoring ceftazidime-avibactam. Pranita Tamma, MD, MHS, continues her conversation about this topic.

Pranita Tamma, MD, MHS, discusses the motivations comparing ceftolozane-tazobactam vs ceftazidime-avibactam and findings of 1 observational study.

Looking at Mortality Rates Comparing Treatments for Gram-Negative Resistant Pseudomonas aeruginosa Infections

This is the first in a series with Pranita Tamma, MD, MHS, associate professor of pediatrics in the Division of Pediatric Infectious Diseases at The Johns Hopkins University School of Medicine, and is a discussion about these antibiotic therapies for gram-negative resistant 

In one retrospective observational study, which compared ceftolozane-tazobactam and ceftazidime-avibactam and was funded by the National Institutes of Health (NIH), the findings showed similar 30-day mortality rates but higher resistance emergence in the ceftolozane-tazobactam group (38% vs 25%). Tamma was the senior investigator in this trial. 

Enclosed below are responses from a conversation with her about this trial as well as other data on this topic.



: What were the key motivations for conducting a head-to-head comparison of ceftolozane-tazobactam and ceftazidime-avibactam in treating difficult-to-treat resistant (DTR) 

We really wanted to compare the clinical outcomes of these 2 drugs that clinicians are preferentially deciding between for treating DTR 

, and we also wanted to understand how likely emergence of resistance will be. We had a smaller previous study that only looked at ceftolozane-tazobactam, but it was 28 patients exposed to this drug and with clinical infections with DTR 

. And we found, surprisingly, that for half of the patients, even though their index 

 isolate was susceptible to ceftolozane-tazobactam, they developed isolates in the next 30 days with resistance to the drug. And it was pretty impressive: The resistance MICs [minimum inhibitory concentrations] would go from 0.5 to greater than 256, so we wanted to see how frequently this actually happened by looking at a larger cohort, although by comparing it with ceftazidime-avibactam. To put the results in context, the study we did was funded by the NIH, and I think that's important because there have been 2 other observational studies in the past year or two that have answered [and] addressed a similar question, comparing outcomes of ceftolozane-tazobactam and ceftazidime-avibactam. We felt that it was important to go into this unbiased. We didn't actually have a hypothesis of which drug might perform better or which drug might lead to less resistance.



The study results found similar 30-day mortality rates between the 2 treatment groups. What does this suggest about their comparative effectiveness in managing DTR infections?

We elected to use 30-day mortality as our primary outcome. Many studies use 90-day mortality. We felt that to really increase the likelihood that the clinical outcome was related to the treatment received, it's nice to have a shorter window. You could imagine these are complex patients, and if we're looking at mortality out to 90 days, we could start to run into issues, like people died because of their underlying cancer, failure of their solid organ transplant, or another infection that they developed. So there's a whole host of reasons we chose the 30-day end point.

We also chose mortality, as opposed to clinical cure, because we feel like it's the most objective end point. There's no subjectivity involved, especially when you're talking about an observational study, which is open label, where we know exactly what people received. You could imagine that most of the patients in our study and the other 2 observational studies recently published had pneumonia. Pneumonia can be very subjective because cultures can stay positive for days or weeks because of colonization, noninfection. Patients can stay on a ventilator because of other underlying conditions. They can stay in the ICU [intensive care unit] because of chemotherapy, adverse events, and all sorts of other reasons like a concomitant influenza infection, etc. It becomes very hard, even if we try to make definitions for clinical cure, to decide, and even in clinical trials, sometimes what the investigators consider cure and independent adjudication committees consider cure have significant differences. So that's why we chose to look at mortality as our primary end point. And you know, it was nice to see that there wasn't a difference in mortality.

As a clinician, I would love to see more drugs available rather than fewer. So at least in the study we performed as well as the 2 other observational studies, none of us found a mortality signal suggesting one of these drugs is more likely to cause poor outcomes vs the other, which I think is a good thing for the infectious diseases community and for patients with these infections.

Pranita Tamma, MD, MHS, discusses the motivations comparing ceftolozane-tazobactam and ceftazidime-avibactam and findings of one observational study.

George Bchech, MD, details his experience as a fellow within the AHN infectious disease-critical care medicine (ID-CCM) fellowship. 

AHN’s ID-CCM Fellowship: The Merits of Dual Training and Treating a Diverse Population 

Allegheny Health Network (AHN) has a unique program in the US that offers a full ID-CCM fellowship. This 3-year training program combines the training of the 2 medical specialties. Their ID-CCM curriculum includes the following:

Inpatient Consult Service: This includes General ID, Solid Organ, Bone Marrow Transplant, and Burn ICU

HIV Continuity Clinic: This is held one-half day per week in the first two years of fellowship

Ambulatory Electives: General ID, Travel Medicine, and Tuberculosis, Clinics

Rotation Electives: Infection Prevention, Antimicrobial Stewardship, Microbiology, International Medicine (Guyana), and Research.


AHN’s fellows have dedicated ICU rotations in their second year to help prepare their transition to the critical care medicine-predominant, third year of fellowship. The third year of medical training is heavily CCM-focused, but time is provided for supplemental training on the ID service.

The combined curriculum provides clinical experience of both specialties, especially in recent years when there was overlap of care related to COVID-19 in patients with severe cases being treated in ICUs, according to one of its current fellows.

“I feel infectious disease and critical care have both come into the limelight post-COVID, because they were the 2 specialties that were needed the most during that time,” said George Bchech, MD, an ID-CCM fellow at AHN.

Bchech points to the benefit of being in a big city hospital environment, and that they are able to see a variety of cases.

“Just being situated in a large city such as Pittsburgh, we have been privileged in seeing varying patient populations and infections,” Bchech said. 

As examples of the diverse population and the novel cases, Bchech says he recently saw 2 cases of malaria as well as seeing patients suffering from the consequences of the opioid epidemic. “Patients come in with wounds that need limb amputations or seeing patients that have ruptured valves because of endocarditis or bloodstream infections,” he said.

Bchech was selected into the Alpha Omega Alpha Honor Medical Society, Drexel College of Medicine Chapter.

“I'm grateful for my program director, Dr Nitin Bhanot, for nominating me for this honorable medical society. What it stands for is leadership, community, continued medical education and research,” Bchech said. And to be able to be part of such a prestigious organization which, represents medicine as a whole…I'm honored to wear that badge with pride.”

In the next episode, Deeksha Jandhyala, MD, discusses how her team works to prevent infections and provide clinical assistance for transplant candidates.

George Bchech, MD, details his experience within the AHN infectious disease-critical care medicine (ID-CCM) fellowship. 

Today, Vir Biotechnology announced the enrollment of the first patient in its ECLIPSE 2 phase 3 trial for chronic hepatitis D (CHD).

 “Patients living with chronic hepatitis delta, a known cause of liver cancer, are waiting for effective options to change the course of their disease,” Vir Biotechnology CEO Marianne De Backer, PhD, MSc, MBA, said in a statement. “We are excited about the rapid progress of our ECLIPSE program, which demonstrates our unwavering commitment to deliver a highly effective treatment for people living with chronic hepatitis delta.”

There are currently no approved treatments in the US for hepatitis D virus (HDV), and options are limited in the European Union and globally.

ECLIPSE 2 will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy. ECLIPSE 1 and 2 are designed to provide the registrational efficacy and safety data needed for potential submission to global regulatory agencies. ECLIPSE 3 is a phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naive patients, and it is designed to provide important supportive data to help establish access and reimbursement in key markets.

ECLIPSE 2 plans to enroll participants in regions where bulevirtide is approved for the treatment of CHD. Participants who do not achieve virologic suppression (defined as failure to achieve HDV RNA target not detected [TND]) after a minimum 24 weeks of bulevirtide treatment will be randomly assigned 2:1 to switch to the combination of tobevibart and elebsiran or continue receiving bulevirtide. The primary end point in ECLIPSE 2 measures HDV RNA at the lower limit of quantification TND, HDV RNA TND (defined as HDV RNA = 0 IU/mL), at week 24.

Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). It is designed to inhibit the entry of hepatitis B and hepatitis D viruses into hepatocytes and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart was identified using the company’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with CHD. 

Elebsiran is an investigational hepatitis B virus–targeting small interfering RNA discovered by Alnylam Pharmaceuticals. It is designed to degrade hepatitis B virus RNA transcripts and limit the production of HBsAg. Current data indicate that it has the potential to have direct antiviral activity against hepatitis B and hepatitis D. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with CHD.

Findings From Screening Study for Hepatitis B and Hepatitis D Demonstrate Need for Follow-Up Testing

Chronic HDV infection is the most severe form of viral hepatitis, with both a poor prognosis and high rates of mortality. And for those patients who have HDV and compensated cirrhosis with clinically significant portal hypertension, they have very limited treatment options. Traditionally, the only therapy available has been the off-label use of pegylated IFN-α, which has demonstrated limited therapeutic responses and an unfavorable safety profile.

Wranke et al showed that having HDV leads to a faster progression to the aforementioned conditions and other liver-related end points.

References
1. Vir Biotechnology initiates second pivotal trial in its global ECLIPSE Registrational Program for chronic hepatitis delta. News release. Vir Biotechnology. July 31, 2025. Accessed July 31, 2025. https://investors.vir.bio/news/news-details/2025/Vir-Biotechnology-Initiates-Second-Pivotal-Trial-in-Its-Global-ECLIPSE-Registrational-Program-for-Chronic-Hepatitis-Delta/default.aspx 
2. Wranke A, Heidrich B, Deterding K, et al. Clinical long-term outcome of hepatitis D compared to hepatitis B monoinfection. 

. 2023;17(6):1359-1367. doi:10.1007/s12072-023-10575-0




The study will examine the switch to the combination of tobevibart and elebsiran in patients not achieving undetectable hepatitis D virus RNA despite bulevirtide treatment.

Emily L. Heil, PharMD, BCPS-AQ ID

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