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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

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.

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

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 on this trial.

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.

Athena Hobbs, PharmD, BCIDP, looked at this issue through the lens of treating urinary tract infections (UTI).

Deciphering When to Use New Novel Agents in Clinical Practice

Since 2024, 3 antimicrobials—gepotidacin (Blujepa), sulopenem etzadroxil and probenecid (Orlynvah), and pivmecillinam (Pivya)—have all been FDA approved and indicated to treat uncomplicated urinary tract infections (UTIs).

Interestingly, Athena Hobbs, PharmD, BCIDP, clinical pharmacy manager and infectious diseases specialist at Cardinal Health, points out the utility to prescribe them now.

“I think these could be used in the outpatient setting quite frequently. This might be an opportunity for us to use a lot of new agents as opposed to keeping them behind that antimicrobial stewardship firewall,” Hobbs said. “The 3 new ones that came out in the last year all target ESBL [extended-spectrum β-lactamase] infections. They're oral options for ESBL, which we already have limited options available [for].”

Hobbs presented at the recent American Society for Microbiology Microbe conference on the topic. She said all of them have potential usage and noted the novelty and potential utility of pivmecillinam.

“Pivmecillinam is really interesting in that it's a very narrow-spectrum agent that targets ESBL infections and uncomplicated urinary tract infections,” Hobbs said.

She noted another favorable aspect of the antimicrobial is that it has been approved and prescribed outside the US for a number of years, which may prove there are more data published or in the process of being studied for different indications, including complicated UTIs, and pivmecillinam does not need to be dose-adjusted for renal dysfunction.

She did acknowledge there is a whole host of challenges to using new antimicrobials, including costs, limited clinical data, and the diagnostic capabilities of the individual institutions.

“A lot of times in these nonacademic medical facilities, they don't necessarily have that kind of testing ability, and so it's a concern. When you get a susceptibility profile, all you have is the phenotypic results, and you see it's resistant to a carbapenem. What do you do next?" Hobbs asked. “In the clinical world, you don't always have the right tools to be able to tell what you need to use.”

In terms of concerns about when to use these new antimicrobials and looking at complicated infections, Hobbs suggested infectious disease teams and microbiologists work together to better understand the pathologies being seen.

“Your infectious diseases [ID] physician [can] partner with your microbiologist to help identify the organism and figure out what are the mechanisms of resistance,” Hobbs said. “Your ID pharmacist can look at the pharmacokinetics and pharmacodynamics of the agents and figure out where we anticipate the agent to be able to get in the body and what kind of infections they might be able to treat.”






Athena Hobbs, PharmD, BCIDP, looked at this issue through the lens of treating urinary tract infections.

Conferences

Deciphering When to Use Novel Agents in Clinical Practice

Emily Olsen, PhD, offers some insights on this underdiagnosed infection, including describing antimicrobial studies, particularly in biofilm and intracellular environments. Her findings look to create a standardized approach for treating all forms of the different presentations of bartonellosis.

Finding a Standard Course of Treatment for Bartonella infections

There are an estimated 7 to 15 different species of 

 Infections with any one of these bacteria are referred to broadly as bartonellosis and include 

infections, also known as cat scratch disease;

It is primarily transmitted by fleas but can also be transmitted by animal bites, scratches, or needle sticks.

infections are transmitted by body lice, with it being unknown how many cases there are, and 

infections are caused by sand flies in some regions of South America.

If these infections progress, they can lead to serious complications and infections, including endocarditis. Patients who are immunocompromised can experience serious clinical manifestations and require antimicrobial treatment. However, there is no standard course of treatment for these infections, and many doctors prescribe antibiotics based on limited data and case studies.

“Severe disease is oftentimes found in immunocompromised patients. And in these patients, they need long, prolonged periods of antibiotics, similar to TB [tuberculosis] infection or 

, the causative agent of Lyme disease,” Emily Olsen, PhD, said in an interview with 

. “And so basically, these patients have to be on antibiotics for long periods, sometimes even 6 months. From my approach, I'm hoping to find a treatment regimen that can essentially treat all forms of the different presentations of bartonellosis

From previous work done by Olsen and Monica Embers, PhD, professor of microbiology and immunology at Tulane University, they discovered that “

 treatment with single antibiotics in different media, as well as in DH82 canine macrophages, was ineffective in eliminating bacteria.”

They decided to expand their work in this area, looking at different antibiotics, which were supported by case reports, as well as double and triple combination therapy in DH82 canine macrophages and biofilms.

 They tested doxycycline, gentamicin, azithromycin, azlocillin, rifampin, tobramycin, and clarithromycin.

“We found that while monotherapy may inhibit growth extracellularly, it is ineffective when used against intracellular bacteria or preexisting biofilms. We found that aminoglycosides in combination with either rifampin or azlocillin significantly reduced bacterial growth in multiple microenvironments,” they wrote.

Olsen and Embers presented these findings at American Society for Microbiology Microbe.

“I'm hoping that the way I approach the problem, which was 167 combinations, essentially, and whittling it down from there, will eliminate any shot in the dark antibiotic treatments, and so it will guide physicians on what patients can take. But of course, everything still has to go through animal models and clinical trials,” Olsen said.

With bartellonosis as an underdiagnosed infection, Olsen believes it is important to recognize how it affects individuals.

 are truly suffering from this disease, and we really need to find an effective approach in treating them,” Olsen said.


References
1. Bartonellosis. Columbia University Medical Center. Accessed August 1, 2025. 

https://www.columbia-lyme.org/bartonellosis


2. About Bartonella. Centers for Disease Control and Prevention. March 3, 2025. Accessed August 1, 2025. https://www.cdc.gov/bartonella/about/index.html
3. Multi-drug therapy is required to effectively treat Bartonella infection in different environments. Presented at: American Society for Microbiology Microbe; June 19-23, 2025; Los Angeles, CA. Session AAR-P-205.



Finding a Standard Course of Treatment for Bartonella Infections

COVID-19 Variants and Vaccine Decisions Heading Into Fall

As new COVID-19 variants circulate and the respiratory virus season approaches, families are once again facing decisions about prevention, especially with schools reopening. Sharon Nachman, MD, division chief of pediatric infectious diseases at Stony Brook Children’s Hospital, shared her perspective on what the latest variants mean for both children and adults and how families can prepare.

Currently, 2 dominant variants are being tracked: Stratus and Nimbus. According to Nachman, both are highly transmissible but not linked to more severe illness compared with earlier strains. “The Stratus variant and the Nimbus variant—those are two of the ones that we're seeing right now—actually are both equally good at infecting a host. They are not, however, associated with more severe illness like we've seen with other strains in the past. So you can easily catch it and you can easily spread it.”

She noted that tracking data shows an upward trend in these variants over the summer: “From May to June to now, in August, we are seeing climbing percentages of both Nimbus and Stratus.” Although hospitalizations have not risen at the same pace, symptoms are shifting. “As part of all the COVID-19 variants that we see, we have seen more sore throat, more hoarseness of throat—that kind of horrible complaint that ‘I can’t talk, I can’t swallow’—happening.”

Though the severity remains relatively mild for most, Nachman cautioned that this could change. “Can this change over the fall and winter? Absolutely it can,” she said. “These variants have many sites of mutation from the original strains that we had back in 2020 as well as in 2022 and 2023.” As she explained, widespread transmission fuels further mutation: “The more people that get it, the more they pass it, the more mutations that happen. So that means the fall and winter are going to be primed for us to see more infections and probably with different variants.”

One practical piece of advice remains consistent. “If you or your child has COVID-19, it would not be a bad idea to stay home until you're not coughing and [you do not] have fever,” she said. This minimizes the risk of passing the virus to others: “They're probably going to pass that variant to the next kid or the next adult—and on and on.”

On the topic of vaccination, Nachman emphasized education as the first step in addressing hesitancy. “Yes, there are several mRNA vaccines out there. mRNA vaccines do not have any mercury in them or thimerosal in them,” she explained. “If it's one vial, one person, there's no thimerosal, there's no preservative.”

She also reassured parents concerned about the safety of mRNA vaccines. “There's nothing live about this vaccine. The vaccine is not going to cause an infection in anyone,” she said. “By giving a COVID-19 vaccine, you turn on the machinery. Unfortunately, when you turn on the machinery, you feel under the weather. You may have some fever and some body aches, but that's because your body is a good immune machine and it's making antibodies.”

Vaccination decisions should take into account both individual and household risk. “We are especially concerned for the fall and winter for older populations as well as populations with underlying lung issues,” she said, noting these groups continue to face higher risks for severe illness and hospitalization.

Although children may typically experience milder symptoms, Nachman urged parents to think about the bigger picture. “In the past, people have said, ‘Oh, kids don't get so sick with COVID-19, they don't need a vaccine.’ As someone who worries about even one child getting sick, I tell families, ‘Think about who your kid is and who else is at home with you.’” For multigenerational households, she recommends considering how one child’s infection could affect more vulnerable relatives. “You may need to circle around that person and have everyone protected so that they're not going to bring it home to that individual.”

Sharon Nachman, MD, breaks down the latest on Stratus and Nimbus variants and what families should consider as schools resume.

Adding oral vancomycin to a systemic antibiotic treatment of a non–

 infection (CDI) to prevent CDI recurrence in at-risk patients was associated with a lower rate of recurrence than in those not receiving vancomycin in a placebo-controlled trial,

 but the difference was not statistically significant and the rates were high in both groups.

"Interventions to prevent recurrent CDI during exposure to systemic antibiotics in a person with prior but not current CDI are needed in clinical practice," Julie Keating, PhD, from the Department of Medicine at the School of Medicine and Public Health at the University of Wisconsin-Madison, and colleagues indicated.

Although the study was underpowered due to challenges in recruiting participants, the investigators found the lack of clear advantage suggested "that other interventions should be investigated for their effectiveness in preventing CDI recurrence after non–CDI-indicated antibiotic therapy."

Keating and colleagues recruited 81 participants with a documented diagnosis of 1 or more CDIs within the past 180 days, completion of a CDI treatment, and receipt of non–CDI-indicated systemic antibiotics for 2 weeks or less and not more than 72 hours at enrollment. The vancomycin group received 125 mg orally daily during and for 5 days after their systemic antibiotic regimen, whereas the control group received placebo in identical capsules. Recruitment challenges, including lack of interest in those with history of CDI to potentially receive placebo, left the size of the cohort 1 less than the minimum calculated to adequately power the study.

With that limitation on drawing conclusions, the investigators reported CDI recurred in 17 of 39 participants (43.6%) in the vancomycin group over the 8-week posttreatment follow-up period compared with 24 of 42 in the placebo group (57.1%). There was a statistically significantly higher rate of carriage of vancomycin-resistant 

(VRE) detected in the gut of those receiving vancomycin (15 of 30; 50%) than those without vancomycin exposure (6 of 25; 24.0%).

 Stuart Cohen, MD, from the Division of Infectious Diseases in the Department of Internal Medicine at the University of California Davis School of Medicine, remarked that although the difference in rate of CDI recurrence between the groups was numerical rather than statistically significant, "the reduction appears to be a clinically meaningful result."

"What is striking, however, is how high the rates of recurrence were in both the treatment (43.6%) and placebo (57.1%) groups," he observed.

Cohen noted that the number of prior recurrences in the participants was not provided, despite risk of recurrence increasing with the number of episodes. He also indicated he would have appreciated the study delving further than VRE colonization to assess overall effect of the vancomycin on fecal microbiota.

Keating and colleagues acknowledged that the study had not evaluated broader effects of the oral vancomycin on the gut microbiome, despite known effects including reduction of baseline commensals, which may facilitate 

"Additional research on patient populations, dosages, and dosing schedules may be needed to determine whether oral vancomycin may provide a greater protective effect within specific parameters while maintaining a low risk profile for patients," they remarked.

1. Keating JA, Xu T, Graham MB, et al. Oral vancomycin for prevention of recurrent 

 infection: a randomized clinical trial. 

. 2025;8(7):e2517834. doi:10.1001/jamanetworkopen.2025.17834

The role of oral vancomycin in preventing recurrence of C difficile infection (CDI) in at-risk persons receiving systemic antibiotic for non-CDI infection remains unclear after randomized trial.

Yoav Golan, MD

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