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Hacker is an infectious diseases clinical pharmacist. She completed her postgraduate year 1 and year 2 infectious disease residencies at UW Health and currently practices at SSM Infectious Diseases Clinic in Madison, Wisconsin.

Doxycycline postexposure prophylaxis is associated with emerging tetracycline resistance in Neisseria gonorrhoeae and commensal organisms, highlighting the need for cautious, targeted use.

The Consequences of Doxycycline Postexposure Prophylaxis

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 US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application for gepotidacin as an oral option for the treatment of uncomplicated urogenital gonorrhea in patients 12 years or older (weighing ≥ 45 kg [99.2 lb]). The GSK antibiotic's FDA application is based on the EAGLE-1 phase 3 trial results published in 

, showing that gepotidacin (oral, 2 doses of 3000 mg) was noninferior, with a 92.6% (187 of 202; 95% CI, 88.0%-95.8%) success rate at urogenital site when compared with a 91.2% (186 of 204; 95% CI, 86.4%-94.7%) success rate for intramuscular ceftriaxone (500 mg) plus oral azithromycin (1000 mg) combined therapy.

Additionally, there were no failures at the urogenital site due to bacterial persistence of 

 in either treatment arm. The safety and tolerability profile of gepotidacin in the EAGLE-1 trial was consistent with results seen in previous clinical trials, with no serious drug-related adverse events observed in either the gepotidacin or the comparator arm. The most common reported adverse reactions were mild to moderate gastrointestinal events.

A Prescription Drug User Fee Act date for an FDA decision is set for December 11, 2025.

The EAGLE-1 study was an open-label noninferiority trial examining oral gepotidacin compared with ceftriaxone plus azithromycin. Participants had to have a body weight over 45 kg, and had suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge), a positive laboratory test result for 

, or both. Patients were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex and sexual orientation.

The primary efficacy end point was defined as eradication of gonorrhea at test of cure (days 4-8). The noninferiority margin was prespecified at –10%. The primary outcome was assessed in the microbiological intention-to-treat population, with all participants randomly allocated to a study treatment who received at least 1 dose of their treatment and had confirmed ceftriaxone-susceptible 

 isolated from the baseline culture of their urogenital specimen, the authors explained.

“Gepotidacin demonstrated noninferiority to ceftriaxone plus azithromycin for urogenital 

, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhea,” the authors wrote.

This is the second major indication filed in the US for gepotidacin. The antibiotic was 

 in March for uncomplicated urinary tract infections (uUTIs).

 A review of regulatory submissions for the uUTI indication is also ongoing in the United Kingdom and Australia.

Deciphering When to Use New Novel Agents in Clinical Practice


References
1. Gepotidacin accepted for priority review by the US FDA for the oral treatment of uncomplicated urogenital gonorrhea. Press release. GSK. August 11, 2025. Accessed August 11, 2025.
https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-the-us-fda-for-the-oral-treatment-of-uncomplicated-urogenital-gonorrhoea/
2. Ross JDC, Wilson J, Workowski KA, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. 

2025;405(10489):1608-1620. doi:10.1016/S0140-6736(25)00628-2
3. Parkinson J. Newly FDA-approved UTI antibiotic shows high efficacy for gonorrhea treatment. 

. April 15, 2025. Accessed August 12, 2025.


https://www.contagionlive.com/view/newly-fda-approved-uti-antibiotic-shows-high-efficacy-for-gonorrhea-treatment

If this GSK antibiotic is approved, it will provide a new oral option to patients in the US who are currently relying on injectable treatments.

FDA Grants Priority Review for Gepotidacin for Gonorrhea

 occurs in up to 40% of healthy adults, but predicting who might go on to develop infection remains a challenge. A new study led by Sean Gibbons, PhD, associate professor at the Institute for Systems Biology, introduces a powerful computational tool to do just that.

Using microbial community-scale metabolic models (MCMMs), Gibbons and colleagues analyzed gut microbiome data from over 15,000 individuals to predict colonization risk and assess how targeted probiotics might help prevent infection before it starts.

In an email interview, we spoke with Gibbons about the implications of this research and how MCMMs might change how we approach 

: Your study introduces MCMMs as a tool to predict individual-specific 

 colonization risk. How do you envision this model being integrated into clinical workflows or screening protocols in the near future?

 This study was preclinical. We were applying MCMMs retrospectively to existing data sets. We would want some additional validation of the predictions before integrating this workflow into clinical practice. For example, we would like to see whether or not our model could predict responders and nonresponders to probiotic therapies designed to treat recurrent 

. These kinds of data do exist from clinical trials, but we haven't yet gotten access to them. If we see sufficient validation, then we would work toward an observational study, where we test our predictions prospectively in a clinical cohort. If that worked out, then we'd move toward an intervention framework, where we used the model to target high-risk patients for intervention and prevention of infection. It's a long path toward translation into the clinic, and our current study represents the first step along that path.

You identified 3 distinct metabolic niches that allow 

 to persist. What are the implications of this metabolic flexibility for treatment strategies, especially in patients without active infection?

 can persist in the guts of many people as a commensal using different growth strategies. This means that interventions that may work for one person to help decolonize them of 

 may not work well in another person. The niche flexibility of 

shows us that personalized prebiotic, dietary, and/or probiotic interventions may be necessary to rescue nonresponders to existing therapies. MCMMs are tools that enable this kind of personalization.

Your findings suggest that targeted probiotics may effectively suppress 

 through metabolic competition. What are the next steps for translating this concept into a clinically viable alternative to fecal microbiota transplantation?

 We will need some additional validation data from retrospective trial data or from prospective human observational cohorts and possibly some animal studies (eg, interventions tested in mice) before we would move into human intervention trials. Even if the data look good, the regulatory landscape for personalized interventions is complex, so there may be some hurdles to overcome before we can routinely implement these kinds of therapies in the clinic. It's a long road, but we're committed to pushing these advances forward.

Given that colonization without symptoms is common, how might your research reshape how clinicians think about the line between colonization and infection and the need for early intervention?

infections are on the decline, community-acquired infections are rising. This is due, in part, to high rates of asymptomatic carriage of 

. We actually think that it might be possible to prevent or reverse asymptomatic carriage of 

 across the population using precision prebiotic, dietary, and probiotic interventions. If we can prevent 

 carriage, we will stop these opportunistic infections before they have a chance to start. This kind of approach could be applied to other opportunistic pathogens as well.

As our understanding of the gut microbiome deepens, tools like MCMMs offer a promising path toward personalized prevention strategies for 

 and other opportunistic infections. While clinical application is still on the horizon, this research marks an important first step in shifting the focus from treatment to early, targeted intervention.

Carr AV, Baliga NS, Diener C, Gibbons SM. Personalized 

 colonization risk prediction and probiotic therapy assessment in the human gut. 

 2025;101367. doi:10.1016/j.cels.2025.101367

A new study finds that personalized gut microbiome models may predict C difficile colonization risk and guide targeted probiotic treatment.

Can We Predict and Prevent C difficile Colonization?

Jose Alexander, MD, offers insights on these antimicrobial combinations when treating infective endocarditis.

Reviewing the Synergistic Activity of  Ampicillin with Cephalosporins, Carbapenems Against Enterococcus faecalis

, which is classified as part of the group D 

inhabits the gastrointestinal tracts of humans.

has been an increasingly common cause of infective endocarditis, with the preferred treatment being a combination of antibiotics.

Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, medical director for the microbiology laboratory at AdventHealth in Orlando, Florida, says that when looking at data from his institution, he approximates that 99% of 

spp. are susceptible to ampicillin (AMP), yet the antimicrobial does not respond because of poor tissue penetration and biofilm formation.

He and his team at AdventHealth wanted to look in vitro at AMP and add another agent, particularly β-lactams when looking at 

“Adding another agent as a synergy that can target a different group of the penicillin-binding protein can help to actually break through and act as a true bactericidal agent,” Alexander said. “Ampicillin is a bactericidal, but it's a possibility that it is acting more as a bacteriostatic in this particular scenario where the immune system is not able to penetrate and biofilm is being formed in endocarditis.”

Alexander and his colleagues compared the activity and potential synergy between AMP with cephalosporins (ceftaroline [CPT] or ceftriaxone [CRO]) and carbapenems (ertapenem [ERTP] or imipenem [IMI]) in vancomycin-susceptible 

 Alexander presented this research at the American Society for Microbiology Microbe conference this summer.

bacteria were obtained from various sources at his institution.

 Antibiotic susceptibility testing was performed. AMP was crossed at organisms' tested minimum inhibitory concentration (MIC), whereas CPT, CRO, ERTP, and IMI were all at MIC of 1 µg/mL or less.

“The combination [of] AMP with cephalosporins demonstrated the most synergy/additive effect with AMP plus CPT at 67% (n = 16), followed by the combination of AMP and CRO at 37.5% (n = 9). AMP and carbapenem combination yielded the fewest effects, with AMP and IMI being the lowest, with no synergy observed,” Alexander et al wrote about their findings.

In terms of his study’s limitations, Alexander acknowledges this was done in vitro and was a very small sampling, but still he points to the potential clinical application.

“I think being able to rule out the presence of antagonism, especially between these β-lactams, gives some peace of mind for clinicians when they decide to combine therapy,” Alexander said. “If they have a patient with endocarditis who is not responding and the organism is susceptible to ampicillin—and they want to implement an antagonist—this can create a synergy activity.”

And he points out this can be done safely.

“We know that even if there is no improved activity between these 2 agents, at least they are not acting against each other. From a clinical perspective, it's also a safety measure, and it's important to have in consideration that antagonism was not observed between these β-lactams,” Alexander said.

https://en.wikipedia.org/wiki/Enterococcus_faecalis


2. What is the best synergistic combination against Enterococcus faecalis? in-vitro synergy activity of ampicillin in combination with cephalosporins and carbapenems for determining synergy, addition, and antagonism. Presented at: American Society for Microbiology Microbe 2025; June 19-23, 2025; Los Angeles, CA.



Jose Alexander, MD, offers insights on these antimicrobial combinations when treating against this bacterium.

Conferences

Reviewing the Synergistic Activity of Ampicillin With Cephalosporins, Carbapenems Against Enterococcus faecalis

It should not have happened, and yet it did. We know better, but we continue to make the same mistakes. Measles (rubeola), the most contagious virus infecting humans (

), remains endemic in many parts of the world. Thanks to highly effective measles, mumps, and rubella (MMR) vaccines, the virus was declared eliminated in the US in 2000.

 Yet, as of August, more than 1300 US cases have been reported in 2025,

with larger outbreaks in Ontario, Canada, and Chihuahua, Mexico.

 Most of the US cases (~ 96%) involve unvaccinated children and young adults—and at least 3 have died. The rise in cases from 2024 highlights the growing threat of declining vaccination rates, travel, and community spread in undervaccinated populations. 

There are many drivers for this situation, including: 

• questioning the need for ongoing vaccination (among the public and some government officials and health care professionals); 

• ongoing circulation of misinformation and disinformation about the safety and effectiveness of vaccination (writ large); 

• mistrust of public health authorities; and 

• vaccine fatigue emerging from the COVID-19 pandemic. 

Measles vaccination is the only available tool to prevent measles infection and its potential complications. Vaccination has been recommended in the US since the 1960s.

 Currently in the US, 2 approved MMR vaccines are available and vaccination is recommended for nearly all children. The standard schedule is for a first dose at 12 to 15 months and a second dose at 4 to 6 years, but the second dose of MMR vaccine can be administered as soon as 1 month after the first dose.

 MMR vaccination is highly effective, with 1 dose resulting in protection of approximately 93% of those vaccinated, and with 2 doses, this increases to approximately 97%.

The MMR vaccine may be given as early as 6 months to prevent disease in unvaccinated persons in an outbreak situation or before international travel, but doses given before 1 year do not provide predictable long-term immunity. Because of this, 2 doses after 1 year are recommended for persons who were vaccinated before their first birthday. MMR vaccination is recommended for adults born since 1957 who do not know whether they have been vaccinated or are immune. The best defense against measles is vaccination, and if individuals are not sure of their immunity or vaccination status, it is safe to get a measles vaccine, unless contraindicated. MMR is a live attenuated vaccine and should not be given to persons with moderate to severe immune suppression or during pregnancy.

There are no specific antiviral drugs approved to treat measles. The goal of medical care is to relieve symptoms and address complications such as bacterial infections that can be serious or even deadly. Severe measles cases among children who are hospitalized may be managed with vitamin A, but this should only be done under the supervision of a health care professional because high-dose vitamin A has potential toxicity and needs to be closely monitored. Vitamin A is not a cure, and it does not prevent measles—only vaccination can do that.

Before the vaccine became available in the 1960s, measles infected nearly every child by their teen years and caused millions of deaths, mostly in children, worldwide each year.

 With improved sanitation, nutrition, and living conditions and the widespread availability of antibiotics for treatment of secondary infections in the US and Europe, measles became much less deadly. Hundreds of thousands of infections continued to occur annually in the US and Europe, but deaths became far less common than they were in countries that did not have these resources. As a result of the improvements in measles outcomes in the US, there was some debate in the 1970s about the need for a universal immunization campaign. Many people thought of measles as a common disease of childhood to be “lived with.” This sentiment did not take into account the deaths, immune system damage (which resulted in many secondary bacterial infections such as pneumonia and ear infections), and the rare but unpredictable and devastating late neurologic complications from measles.

 Most persons born in the US before 1957 have lifelong immunity from childhood infection. Measles was endemic in the US before this time, and most were infected during childhood. The first measles vaccines (one inactivated and another live attenuated measles vaccine) became available in the US in 1963.

 The inactivated vaccine was effective but did not result in long-lasting immunity. Early live attenuated vaccines were much more reactogenic.

 Further vaccine development and virus strain attenuation resulted in safer vaccines and ultimately led to the development and introduction of the combined MMR vaccine. With the widespread introduction of the measles vaccine in the US, the incidence of disease fell rapidly, but disease elimination in the US took much longer. Public uptake of the vaccine remained below goals due to cost and low demand. It was not until school vaccination requirements and permanent federal funding were established that the US was able to declare measles eliminated (defined as the absence of continuous disease transmission for 12 months or more in a specific geographic area).

Global efforts to eliminate measles are ongoing,

A preventable crisis, measles, makes a dangerous comeback.

Larissa Hacker, PharmD, BCIDP

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