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Director of the Pharmacometric Center of Excellence at Midwestern University and ID Clinical Pharmacist.

At MAD-ID, Marc Scheetz, PharmD, discusses how PK/PD modeling and AUC-based strategies offer safer, more precise antibiotic therapy.







Precision in Practice: PK/PD Modeling Advances Infectious Disease Care

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

Logan Brock, PharmD, presents UF Health Shands data at MAD-ID 2025 showing limited diagnostic yield from routine fungal cultures and delayed results compared to standard methods.

A retrospective analysis from UF Health Shands Hospital questions the clinical value of routinely ordering fungal blood cultures alongside standard blood cultures during initial sepsis evaluations. The findings, presented by Logan Brock, PharmD, at MAD-ID 2025, show that fungal blood cultures rarely provide additional diagnostic information and take longer to yield results.

The single-center study reviewed 2,073 adult inpatient encounters from January 1, 2023, to December 31, 2024, in which fungal and standard blood cultures were collected within 24 hours of each other. Of those, 96.9% showed no growth in either type of culture. Among the 64 pairs that did show growth, only 8 (12.5%) fungal cultures were positive when standard cultures were negative. Conversely, 30 (46.9%) standard cultures identified fungal pathogens that fungal cultures missed. Both cultures were positive in 26 (40.6%) cases. 

 species accounted for 93.8% of all fungal isolates.

Median time-to-positivity was significantly longer for fungal cultures (48 hours; IQR: 41–93) than for standard cultures (33 hours; IQR: 28–43; 

 < 0.001). All-cause in-hospital and 30-day mortality rates were 17.4% and 16.4%, respectively.

“Paired fungal blood cultures infrequently identified fungal pathogens not detected by standard blood cultures and had a longer time-to-positivity,” the authors concluded.

Logan Brock, a PGY-2 infectious diseases pharmacy resident at UF Health Shands, said the study originated from concerns raised by an ICU pharmacist, “One of our ICU pharmacists reached out to us because she was seeing an increase in fungal blood cultures being ordered at our hospital. So, us and the ID stewardship department did a little digging with her, and we confirmed that there were actually a lot of fungal blood cultures being ordered. Anecdotally, we weren’t seeing a lot of fungal growth from these fungal blood cultures. Even in the cases where they did grow, the standard blood cultures were also growing the fungus. So, we wanted to take a closer look at our hospital’s fungal blood culture ordering and see if they’re providing any utility—or perhaps not.”

While no formal restrictions have been implemented yet, Brock says discussions are underway, “Full disclosure—at my hospital, we haven’t decided how we’re going to restrict fungal blood cultures based on the results of this study. There are a lot of key stakeholders that will have to get engaged—ID physicians, ICU doctors who are ordering the fungal blood cultures.”

He noted that one possible model could mirror how the hospital managed anaerobic blood culture bottles during a supply shortage, “Some ideas we’ve been talking about are doing something similar to what we did with our anaerobic blood culture bottles during the shortage… so that any people or teams who wanted to order anaerobic bottles had to request them from the micro lab—and usually had to show that they had some indication for them, like intra-abdominal infections… I can see doing something similar for fungal blood cultures.”

Despite the low yield overall, Brock emphasized that fungal blood cultures may still be valuable in select high-risk patients. He shared one case in which they led to a meaningful therapeutic adjustment.

“Yeah, so there was actually one case in particular where fungal blood cultures provided a really big benefit, I would say. This was a 73-year-old patient who came in septic. He had a bowel perforation, so he was started on fungal coverage. Predictably and appropriately, standard blood cultures were drawn, fungal blood cultures were drawn, and the standard blood cultures grew a couple of bacteria—

“The fungal blood culture did actually grow a 

 ended up being 32, which is susceptible dose-dependent. It is susceptible, but it’s right at the breakpoint for susceptible—so it’s a very high MIC.

“Based on those results, we switched him from fluconazole to our echinocandin at our hospital, micafungin, which I think was a much better therapy. Their white count came down, they improved, and I think without using fungal blood cultures there, we might not have known they had a fungal infection at all.” The findings support targeted, rather than routine, use of fungal blood cultures, especially in patients without clear risk factors for invasive fungal disease

Brock L, DeSear K, Engeleit A, Gurram P, Vuong L. Under the Microscope: The (Over)Utilization of Fungal Blood Cultures. Abstract 46 OR FRS. MAD-ID Meeting. May 28–31, 2025. Orlando, FL.

Logan Brock, PharmD, presents data at MAD-ID 2025, showing limited diagnostic yield from routine fungal cultures and delayed results compared with standard methods.

Conferences

Rethinking Fungal Blood Cultures in Sepsis Workups

In the first quarter of 2025, California reported 3,123 cases of Valley Fever (Coccidioidomycosis), nearly double the 10-year average for this period. This is the highest number reported for Q1 on record, surpassing the previous record of 3,011 cases in 2024. Following a record-breaking year in 2024 with 12,637 cases statewide, experts warn California may be on track to exceed last year’s total. Updated reports are still being anticipated. 

Monterey County, CA, has seen a particularly sharp increase. In the first quarter of 2023, only 22 cases were reported. By the same period in 2025, the number had surged to 217. This increase is part of a larger trend of rising cases across the state, with some areas of the Central Valley seeing a 200% increase in cases over the past year.

Valley Fever primarily affects the respiratory system, often presenting with flu-like symptoms. However, severe cases can lead to more serious conditions, including pneumonia that requires ventilator support. “We’re concerned that not only are there more cases, but there’s more severe disease,” said George Thompson, MD, professor of infectious diseases at UC Davis Medical Center in our January 2025 interview.

In approximately 1% of cases, Valley Fever can spread from the lungs to other organs, including the brain, bones, and skin, potentially leading to meningitis. The rising number of cases and severity of the disease has resulted in increased admissions to intensive care units (ICUs). “We haven’t typically had this many patients with Valley Fever in the ICU at one time,” Thompson added.

Environmental Factors Contributing to Spread

Several environmental factors are contributing to the rise in Valley Fever cases. The disease is caused by inhaling spores from the Coccidioides fungus, which thrives in dry, dusty regions. Experts point to the state’s fluctuating climate as a key factor. Wet conditions promote the growth of fungal spores, which are then released into the air when disturbed by human activities or natural events, such as wildfires.

Thompson noted that, “In the soil, Coccidioides exists as a mold form. And during periods of heavy precipitation, when we get a good amount of rainfall, we think it grows into a higher quantity within the soil. And then during drought conditions, every other cell dies and spores are formed.” These spores can then be inhaled, causing infection.

Wildfires, which have increased in California due to long droughts, may also contribute to the spread of Valley Fever. “Fire can create its own weather. It kind of updrafts air, and we’re concerned that those large updrafts might throw Valley Fever into the air and really facilitate spread into the surrounding region,” Thompson said.

Emerging research also points to previously unrecognized environmental risk areas. In a recent study, we interviewed Jane Sykes, BVSc (Hons), PhD, MPH, MBA, from school of veterinary medicine, UC Davis School of Veterinary Medicine, and she analyzed over 830,000 canine serologic tests from across the US, finding that 

 is likely present in far more counties than previously detected by human surveillance alone. The number of US counties with seropositive dogs increased more than five-fold over the past decade, from 76 counties in 2012 to 390 counties in 2022.

“The dog serologic data analysis showed that the incidence in dogs closely follows that in humans, at least in California and Arizona,” Sykes said. This suggests that canine seropositivity could serve as a proxy for human exposure in areas where testing and reporting are limited. “We are currently performing additional studies with the data to extrapolate where unrecognized disease might be occurring in humans—both in locations where reporting is required and in other parts of the country.”

Sykes emphasized that integrating veterinary and human data through a One Health approach could improve early detection and inform occupational health strategies in emerging risk areas. “There may be implications for occupational exposure reduction, such as education of construction workers, military personnel, agricultural workers, or wildfire fighters regarding the need for PPE and dust avoidance,” she noted.

Certain occupations and regions are at higher risk for Valley Fever. People working in construction, firefighting, and archaeology are particularly vulnerable due to their frequent exposure to disturbed soil. Additionally, residents of dry, arid areas, such as those in Central and Southern California, are at increased risk.

Valley Fever is typically treated with antifungal medications such as fluconazole and itraconazole, but some patients do not respond to these treatments, complicating management.

 “Some of those patients don’t respond to any agent, and that’s really a challenge for how we improve these patients,” Thompson explained. In these cases, immunotherapy may be used to enhance the body’s immune response.

Health officials have issued several recommendations to reduce the risk of infection, particularly in dust-prone areas. Monterey County has advised local medical providers to be vigilant and issued guidance urging residents to avoid dust exposure. At events like the Lightning in a Bottle festival, organizers are taking steps to reduce dust, including watering the grounds and using artificial turf.

To prevent infection, health experts recommend limiting exposure to dust, especially during dry conditions or after rainfall. Individuals who live in or visit areas with a high risk of Valley Fever should be alert to flu-like symptoms, including cough, fever, chest pain, and fatigue. Early medical consultation is essential if symptoms worsen or do not improve.

1. California Department of Public Health. Provisional Valley Fever Cases in California – As of March 31, 2025. California Department of Public Health. Updated April 16, 2025. Accessed May 20, 2025. 

https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/ValleyFeverProvisionalDashboard.aspx

2. Abene S, Thompson G. Dusty fungal threat: Valley fever spreads as conditions change. Contagion. January 24, 2025. Accessed May 20, 2025. 

https://www.contagionlive.com/view/dusty-fungal-threat-valley-fever-spreads-as-conditions-change

3. Abene S. Canine serology sheds light on underreported human coccidioidomycosis spread. Contagion. April 11, 2025. Accessed May 20, 2025. 

https://www.contagionlive.com/view/canine-serology-sheds-light-on-underreported-human-coccidioidomycosis-spread

4. Centers for Disease Control and Prevention. Valley fever (coccidioidomycosis). April 24, 2024. Accessed May 20, 2025. 

https://www.cdc.gov/valley-fever/about/index.html

The state reported 3123 cases, a significant jump from 2024's 1011 cases in the same period, with experts citing environmental factors.



California Valley Fever Cases Surged in Q1 2025 Compared to Last Year

Investigators have identified the mechanism behind drug resistance for treating mycetoma caused by 

 Mycetoma can be a severe, chronic disease and is frequently drug-resistant to standard treatment with itraconazole when it is caused by this particular fungus. 

The mechanism of resistance is an additional gene encoding a variant of cytochrome P450 14-α sterol demethylase. Using genetic engineering, protein modeling, and computer simulations, the Chiba team demonstrated how this second gene reduces treatment effectiveness, guiding the development of future effective therapies.

To treat the fungal form of mycetoma, known as eumycetoma, clinicians have typically used itraconazole—an antifungal medication that targets a key fungal enzyme. However, when the disease is caused by 

, a lesser-known fungal species, this has often shown resistance to itraconazole, leaving patients with few treatment alternatives. Until recently, the reasons behind this resistance remained poorly understood.

This new research included different universities and was led by associate professor Takashi Yaguchi, PhD, the Medical Mycology Research Center, Chiba University. Together, they investigated the molecular mechanisms behind itraconazole resistance in 

Using genome sequencing and genetic engineering techniques, the researchers identified that, unlike its treatable cousin 

 possesses an additional gene encoding the enzyme cytochrome P450 14-α sterol demethylase (CYP51). This second copy of the 

), which encodes the specific target of itraconazole, has key functional and structural differences compared to the gene common with 

), effectively neutralizing the drug’s impact.

The team confirmed their discovery through multiple approaches. They demonstrated that both copies of the gene become more active when the fungus is exposed to itraconazole, with the unique 

 gene showing particularly strong activation—a typical defensive response. When the researchers transplanted these genes into yeast cells for further testing, cells carrying the 

 gene were markedly less susceptible to itraconazole compared to those with the standard gene version.

According to the Centers for Disease Control and Prevention (CDC), mycetoma is a chronic, progressive subcutaneous skin infection that can be caused by bacteria or fungi.

 Characterized by painful swelling, skin nodules, and pus-discharging sinuses, the condition primarily affects individuals who come into frequent contact with soil, such as agricultural and manual workers. Despite its serious health and socioeconomic consequences, mycetoma has been largely overlooked by global medical research, resulting in limited diagnostic tools and few effective treatment options.

 If left untreated, mycetoma can spread into tissues or bone and can lead to disability. And in some cases, lead to amputation.

Mycetoma affects thousands of people living in tropical and subtropical regions, particularly those in low-resource settings.

CDC says it primarily affects low-income agrarian populations in tropical regions. Endemic countries are called the Mycetoma Belt and include Venezuela, Chad, Ethiopia, India, Mauritania, Mexico, Senegal, Somalia, Sudan, and Yemen. 

Not much is known about mycetoma’s transmission, risk factors, or pathogenesis.

CDC explains that mycetoma is caused by a diverse group of microorganisms. The predominant etiologic agent varies by geographic region. Fungal mycetoma (eumycetoma) and bacterial mycetoma (actinomycetoma) cause disease in Africa and Asia, while bacterial mycetoma (actinomycetoma) causes the majority of cases in South and Central America.

In 2016, the World Health Organization added mycetoma to its list of neglected tropical diseases, which is a significant step to better understand the disease and to establish prevention recommendations, and to improve upon diagnostics and therapies for it.

This research marks a significant step forward in addressing a severe disease that primarily affects impoverished communities. By understanding how drug resistance develops at the molecular level, scientists can work on targeted approaches to overcome it. “Our findings will hopefully pave the way for more effective treatment strategies for eumycetoma caused by

References
1.Uncovering the Shield: Gene Duplication Behind Antifungal Resistance in Madurella fahalii. Chiba University. May 22, 2025.

Accessed May 26, 2025.

2.Clinical Overview of Mycetoma. CDC. April 24, 2024. Accessed May 26, 2025.
https://www.cdc.gov/mycetoma/hcp/clinical-overview/index.html

A published study reveals how an extra gene allows a specific mycetoma-causing fungus to neutralize itraconazole when treating the neglected tropical disease.

Gene Duplication Is Mechanism for Antifungal Resistance in Madurella fahalii-Caused Mycetoma

The federal agency has given the nod to the latest Moderna COVID-19 vaccine mRNA-1283 (mNEXSPIKE). This becomes the first vaccine approved under the new federal guidelines that change who is eligible for the immunizations. The vaccine is indicated for use in all adults 65 and older, as well as individuals aged 12-64 years with at least 1 or more underlying risk factor as defined by the Centers for Disease Control and Prevention (CDC).

"The FDA approval of our third product, mNEXSPIKE, adds an important new tool to help protect people at high risk of severe disease from COVID-19," Moderna CEO Stéphane Bancel, said in a statement.

 "COVID-19 remains a serious public health threat, with more than 47,000 Americans dying from the virus last year alone."

The new approval is based on results from a randomized, observer-blind, active-controlled phase 3 clinical trial, which enrolled approximately 11,400 participants aged 12 years and older. The primary efficacy objective in this study was to demonstrate the non-inferior vaccine efficacy against COVID-19 starting 14 days after mNEXSPIKE compared to that after the comparator vaccine, mRNA-1273 (Spikevax), Moderna's original COVID-19 vaccine. 

Participants received either a 10 μg dose of mRNA-1283 or a 50 μg dose of mRNA-1273. mRNA-1283 showed a 9.3% higher relative vaccine efficacy (rVE) compared to mRNA-1273 in individuals aged 12 years and older, and in a descriptive sub-group analysis, a 13.5% higher rVE in adults aged 65 and older.

In this trial, mRNA-1283 was found to have a similar safety profile to mRNA-1273, with fewer local reactions and comparable systemic reactions. The most commonly solicited side effects were injection site pain, fatigue, headache and myalgia.

Moderna said it expects to have the mRNA-1283 vaccine ready in the US for the 2025-2026 respiratory virus season. Additionally, the vaccine is under review with regulators in multiple markets around the world.

Earlier this week, the leaders of the NIH, HHS, and FDA, announced the removal of the COVID-19 vaccine from the immunization schedule for pregnant women and healthy children in a social media post. 

However, since that post, the federal government has yet again changed its stance on the vaccine and healthy children. In fact on the CDC's Child and Adolescent Immunization Schedule by Age, the COVID-19 vaccines will be available to the pediatric population under what is 

 in the guidance. This addresses children ages 6 months –17 years who are not moderately or severely immunocompromised, and it says the following: "Shared clinical decision-making vaccinations are individually based and informed by a decision process between the health care provider and the patient or parent/guardian. Where the parent presents with a desire for their child to be vaccinated, children 6 months and older may receive COVID-19 vaccination, informed by the clinical judgment of a healthcare provider and personal preference and circumstances," the CDC says on the website. 




References
1. Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE. Moderna press release. May 31, 2025. Accessed May 31, 2025.
https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S--FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx
2.Prasad V, Makary MA. An Evidence-Based Approach to Covid-19 Vaccination. 

. Published online May 20, 2025. doi:10.1056/NEJMsb2506929



The company's vaccine, mRNA-1283, becomes the first approval under the new federal guidelines.

FDA Approves Moderna’s COVID-19 Vaccine

Paul Feuerstadt, MD, discuses the treatment’s overall safety and efficacy profile as well as looking at smaller subsets of patients with comorbidities.

Reviewing Real-World Safety and Efficacy Data on C difficile Therapy Rebyota

Fecal microbiota, live-jslm (Rebyota [RBL]), which is indicated for treatment of recurrent 

has been FDA approved for over 2 years now, and with it comes real-world efficacy and safety data. 

Paul Feuerstadt, MD, FACG, AGAF, associate clinical professor of Medicine at Yale School of Medicine, has been involved with studies around this therapy for several years, and believes the product is very safe and effective.

He provides details about an abstract presented at the Digestive Disease Week conference that looked at 5 prospective trials, including 2 randomized control trials and multiple open label studies. “It was an integrated safety analysis of those trials, including 1,192 individuals who received at least of 1 dose of RBL, 769 who received 1 dose of RBL, and 83 who received placebo. And then in effect, showed that there was consistency of adverse events between the placebo and those who received RBL, and that consistency shows that RBL doesn't leave patients at greater risk for adverse events and serious adverse events,” Feuerstadt said. “Serious adverse events were 11.2% for a single dose of RBL, and 7.2% for a single dose of placebo.”

Paul Feuerstadt, MD, discuses the treatment’s overall safety and efficacy profile and provides insights on data around smaller subsets of patients with comorbidities.

Marc H. Scheetz, PharmD, MSc

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