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New public health perspectives on aspergillosis, sporotrichosis, histoplasmosis, and coccidioidomycosis.

Four Fungal Horsemen: Emerging Trends in Fungal Disease Epidemiology

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

TAXIS Pharmaceuticals announced it has received a $2.9 million grant, to be awarded over 3 years, from the National Institute of Allergy and Infectious Diseases, one of the institutes of the National Institutes of Health (NIH). This grant will allow the company to further advance research and development for its dihydrofolate reductase inhibitors (DHFRIs) as a novel approach to combat multidrug-resistant gonorrhea (MDRG, commonly referred to as 

), a rapidly spreading, deadly, and highly resistant strain of 

“Our DHFRIs have demonstrated preclinical potential in overcoming resistance barriers, offering a significant breakthrough for future treatment,” TAXIS Chief Scientific Officer Ajit Parhi, PhD, said in a statement. “This NIH grant further validates our scientific approach and the vital role that DHFRIs can play in addressing this growing public health challenge.”

DHFRIs target and inhibit the essential bacterial enzyme DHFR, thereby blocking DNA, RNA, and protein synthesis, resulting in cell death. TAXIS’ oral, first-in-class investigational DHFRIs targeting MDRG successfully eradicated MDRG in animal efficacy models.



"Super Gonorrhea" Is Evolving as a Greater Treatment Challenge

This newer strain of the sexually transmitted infection (STI), also known as super gonorrhea, poses a public health challenge due to its resistance to the last line of effective antibiotic, ceftriaxone. And the overall incidence rates of this STI are escalating worldwide. The World Health Organization (WHO) reports that in 2020, there were an estimated 82.4 million (47.7 million-130.4 million) new gonorrhea cases among people aged 15 to 49 years worldwide, with a global incidence rate of 19 (11-29) per 1000 women and 23 (10-43) per 1000 men. Most cases were in the WHO African Region and Western Pacific Region.

Although the MDRG strain has been seen mostly outside the US, in 2023, 2 cases of this pathogen were confirmed in the US and identified by the Massachusetts Department of Public Health.

Massachusetts officials reported that clinicians were able to treat the patients successfully with ceftriaxone. However, this strain of the STI had reduced susceptibility to 5 antibiotic classes—including cephalosporins.

TAXIS, a clinical-stage company at the forefront of developing therapies, is developing new classes of antiresistance therapies to treat life-threatening multidrug-resistant bacterial infections. Their investigational drug candidates include efflux pump inhibitors, DHFRIs, and FtsZ inhibitors and aim to combat antimicrobial resistance (AMR).

The company sees the importance of addressing AMR for this form of STI but also antimicrobial development overall.

"This NIH grant is a critical step in enabling TAXIS to tackle the urgent threat posed by super gonorrhea," TAXIS Pharmaceuticals CEO Gregory Mario, MBA, said in a statement. “Effective antibiotics are the foundation of modern medicine. Along with other innovative pharmaceutical and biotechnology companies, we are committed to solving the antimicrobial resistance crisis— the No. 1 threat to global societal health.”


References

1. TAXIS Pharmaceuticals announces $2.9 million NIH grant for its novel investigational therapeutic to combat antibiotic-resistant gonorrhea. Press release. TAXIS Pharmaceuticals. May 27, 2025. Accessed May 27, 2025.
2. Multi-drug resistant gonorrhea. World Health Organization. July 11, 2023. Accessed May 27, 2025. 

https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea


3. Landhuis EW. Multidrug-resistant “super gonorrhea” rallies multipronged effort. 

 2024;331(20):1695-1697. doi:10.1001/jama.2023.15355



TAXIS Pharmaceuticals announced it received a $2.9 million federal grant, which will allow the company to further advance its efforts with its dihydrofolate reductase inhibitors for the rapidly spreading and antibiotic-resistant strain of Neisseria gonorrhoeae. 

Company Receives NIH Grant for Novel Investigational Antibiotic to Combat "Super Gonorrhea"

Today, Spero Therapeutics and GSK announced their PIVOT-PO phase 3 study was stopped early for efficacy following review by an independent data monitoring committee (IDMC) that completed a prespecified interim analysis of participants enrolled in the trial.

The trial met the primary end point of noninferiority of oral tebipenem pivoxil hydrobromide (HBr) compared with intravenous imipenem-cilastatin in hospitalized adult patients with complicated urinary tract infection (cUTI), including pyelonephritis, on overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit. 

In terms of safety, the IDMC review did not identify any new concerns beyond what has been reported in other studies with the antibiotic, which included diarrhea and headache as the 2 most reported adverse events.

“Achieving the primary end point in the PIVOT-PO trial marks a significant milestone for tebipenem HBr,” Spero CEO Esther Rajavelu said in a statement. “If approved, we believe tebipenem HBr is well positioned to change the treatment landscape for patients diagnosed with cUTI, including pyelonephritis.”

Tebipenem HBr is a late-stage development asset developed in collaboration with GSK.

PIVOT-PO is a global, randomized, double-blind, pivotal phase 3 clinical trial of oral tebipenem HBr vs intravenous (IV) imipenem-cilastatin in hospitalized adult patients with cUTI including pyelonephritis. Patients were randomly assigned 1:1 to receive tebipenem HBr (600 mg) orally every 6 hours or IV imipenem-cilastatin (500 mg) every 6 hours for a total of 7 to 10 days. The primary efficacy end point is overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit.

The primary analysis for the trial is an assessment of noninferiority (NI) in the microbiological intention-to-treat population based on a 10% NI margin. The trial enrolled a total of 1690 patients, with random assignment stratified by age, baseline diagnosis (cUTI including pyelonephritis), and the presence or absence of urinary tract instrumentation.

An estimated 2.9 million cases of cUTIs are treated annually in the US alone.

cUTIs account for over 626,000 hospital admissions annually in the US, representing approximately 1.8% of all hospitalizations, and 80% of these cases are not catheter related.

 “Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock,” GSK Chief Scientific Officer Tony Wood said in a statement. “Currently, many need hospital-based intravenous treatment due to limited oral options for drug-resistant infections, contributing to over $6 billion per year in US health care costs.”

GSK plans to work with US regulatory authorities to include the data as part of a filing for FDA approval in the second half of 2025. "We look forward to working with GSK on next steps for this program,” Rajavelu said.



References

1. Spero Therapeutics and GSK announce PIVOT-PO phase 3 study for tebipenem HBr stopped early for efficacy following review by independent data monitoring committee. Press release. Spero Therapeutics Inc. May 28, 2025. Accessed May 28, 2025.
https://www.globenewswire.com/news-release/2025/05/28/3089331/0/en/Spero-Therapeutics-and-GSK-Announce-PIVOT-PO-Phase-3-Study-for-Tebipenem-HBr-Stopped-Early-for-Efficacy-Following-Review-by-Independent-Data-Monitoring-Committee.html
2.

Carreno JJ, Tam IM, Meyers JL, Esterberg E, Candrilli SD, Lodise TP Jr. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. 

. 2019;6:ofz446.
3. Sabih A, Leslie SW. Complicated urinary tract infections. In: 

. StatPearls Publishing; 2025-. Updated December 7, 2024. https://www.ncbi.nlm.nih.gov/books/NBK436013/

If approved, Spero Therapeutics and GSK’s antibiotic, tebipenem HBr, could be the first oral carbapenem for US patients with complicated urinary tract infections (cUTIs).

Investigational cUTI Antibiotic Meets End Point, Phase 3 Study Stopped Early

Sputum cultures obtained before rather than after initiating antibiotic treatment were found to detect more respiratory pathogens and fewer opportunistic bacteria of uncertain clinical relevance in findings from a study

of over 15,000 patients that support the intuitive choice of culturing prior to treatment when possible.

"While the recommendation to collect sputum samples before antibiotic treatment is intuitive, supporting research is inadequate and is based on study cohorts limited in size and statistical power or specific patient groups," point out Magnus Paulsson, DMSc, associate professor of infection medicine in the Department of Clinical Sciences at Lund University in Sweden, and colleagues. "Understanding the impact of antibiotics on sputum culture results is important for interpretation of culture results and deciding how to act on the result."

Paulsson elaborated on the need to cautiously interpret sputum culture results obtained after initiating antibiotics in comments on the study with 

"When a microbiology laboratory reports the presence of opportunistic pathogens in a sputum sample collected after the initiation of antibiotic therapy, several interpretations are possible," Paulsson explained. "One possibility is that the reported organism is the true causative agent of the infection and antibiotic therapy should be adjusted accordingly. However, there is also a significant risk that the organism is not the actual pathogen. Misinterpretation in such cases can lead to unnecessary broadening of antibiotic coverage, which may contribute to antimicrobial resistance and other complications."

"It is essential to consider the timing of sample collection, the patient's clinical status, and the likelihood of colonization vs infection before modifying antibiotic therapy based solely on culture results," Paulsson advised.

In adding to evidence of the advantage of prior culturing, however, the investigators acknowledge that such timely collection can be challenging for several reasons, including patients unable to expectorate spontaneously, overcrowded emergency departments with limited feasibility of assisted airway clearance, and the clinical necessity of immediate empirical antibiotic therapy or respiratory support.

In their retrospective cohort study of 21,364 sputum cultures from 15,366 individuals at 9 hospitals over a period of 10 years (2011 to 2021), 46% were obtained with recent or ongoing antibiotic use. For their analysis, they classified antibiotic exposure as none, ongoing (oral antibiotics within 7 days or intravenous within 24 hours), or recent (treatment concluded within 30 days and prior to the criteria for ongoing).

Paulsson and colleagues reported that sputum cultures collected prior to initiating antibiotics revealed respiratory pathogens in 26.4% of samples compared with 12.2% of cultures taken after antibiotic exposure. Opportunistic pathogens were more frequently detected after recent antibiotic exposure.

The most frequently detected respiratory pathogens were 

, but the investigators found that each elapsed hour after antibiotic administration significantly decreased the probability of detecting either. In contrast, they noted, detection of opportunistic organisms except for 

"Collecting samples after antibiotics have been initiated may reduce diagnostic accuracy and potentially increase the yield of opportunistic pathogens, counteracting the goals of stewardship," the investigators concluded.

In addition to advising cautious interpretation of sputum cultures obtained after starting antibiotics, Paulsson suggested that amending practice guidelines might be warranted.

"Personally, I think that guidelines could be updated and that posttreatment samples should only be sent for cultures in select cases; for instance, from patients with chronic pulmonary diseases and pneumonia, very severe disease, or when nonsusceptible organisms are expected," Paulsson said.

1. Bryer M, Johansson E, Ryden H, et al. Sputum culture yields after antibiotic therapy – a retrospective cohort study. 

Study findings underscore value of obtaining sputum culture prior to initiating antibiotics for greater detection of pathogens without opportunistic bacteria of uncertain clinical relevance.

Value of Sputum Cultures Diminished by Prior Antibiotics

A newer FDA-approved antibiotic, sulopenem (Orlynvah), was found to be noninferior to a long-standing treatment, amoxicillin/clavulanate (Augmentin), in adult women with uncomplicated urinary tract infections (uUTIs), according to data from the REASSURE phase 3 trial. The results were published in the 

“Overall success in the microbiologic-modified intent-to-treat population occurred in 318 of 522 (60.9%) participants treated with sulopenem versus 260 of 468 (55.6%) participants treated with amoxicillin/clavulanate (difference, 5.4 percentage points; 95% confidence interval [CI], −0.8 to 11.5), meeting criteria for noninferiority,” the investigators wrote.

Iterum Therapeutics developed sulopenem—its first compound—which is a novel penem anti-infective compound with an oral formulation and intravenous formulation. “We are very pleased that 

 has published the results from the REASSURE trial,” Iterum CEO Corey Fishman said in a statement. “This article highlights the need for new antibiotics, like Orlynvah, for the treatment of uUTI given the increasing rates of multidrug resistance to the currently available antibiotics. We expect Orlynvah to be available to treat women with hard-to-treat infections in the next quarter.”

The REASSURE trial included 2222 adult women with uUTIs, and the median age was 51 years. Participants were randomly assigned to receive either treatment for 5 days. The trial's primary end point was the overall response rate at the test-of-cure visit. 

In terms of adverse events, there were more experienced in the sulopenem group. “Treatment-emergent adverse events occurred more frequently with sulopenem compared with amoxicillin/clavulanate, including diarrhea (8.1% vs. 4.1%), nausea (4.3% vs. 2.9%), and headache (2.2% vs. 1.5%),” the investigators wrote.

UTIs are among the most common infections encountered. There are approximately 15 million emergency department and office visits for symptoms of UTIs and over 40 million total prescriptions for uUTIs in the US annually, with approximately two-thirds or 26 million of those prescriptions written for patients who are at elevated risk for treatment failure, based on market research.

Resistance was also seen in the REASSURE trial. “Ninety-one (9.2%) patients in the primary population (microbiologic-modified intent-to-treat population), the combined population of patients with a positive baseline urine culture and without regard to amoxicillin/clavulanate susceptibility, had a baseline pathogen resistant to three or more classes of antibiotics,” the investigators wrote.

Antibiotic Resistance in the Context of UTI Treatment Developments

Oral sulopenem from Iterum Therapeutics was FDA approved last fall for uUTIs in adult women caused by specific bacteria, including 

, when there are limited or no alternative oral antibiotic options.

“As the first oral penem approved in the US, Orlynvah offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market. With FDA approval and a clear label, we will renew our efforts to achieve a strategic transaction involving Orlynvah with the goal of maximizing value for our stakeholders,” Fishman said in a statement at the time of the approval.

Puttagunta S, Aronin SI, Gupta J, Das AF, Gupta K, Dunne MW. Sulopenem versus amoxicillin/clavulanate for the treatment of uncomplicated urinary tract infection. 

. 2025;4(7):EVIDoa2400414. doi:10.1056/EVIDoa2400414
2. Iterum Therapeutics announces publication of REASSURE trial in NEJM Evidence. News release. Iterum Therapeutics. June 25, 2025. Accessed June 25, 2025. https://ir.iterumtx.com/press-releases/detail/150/iterum-therapeutics-announces-publication-of-reassure-trial
3. Iterum Therapeutics receives U.S. FDA approval of ORLYNVAH (oral sulopenem) for the treatment of uncomplicated urinary tract infections. News release. Iterum Therapeutics. October 25, 2024. Accessed June 25, 2025. 

https://www.iterumtx.com/news/press-releases/detail/136/iterum-therapeutics-receives-u-s-fda-approval-of

Marketed as Orlynvah, oral sulopenem from Iterum Therapeutics was FDA approved last fall for uncomplicated urinary tract infections and has shown efficacy against infections caused by Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis.

Sulopenem Is Noninferior to Amoxicillin/Clavulanate for Uncomplicated UTIs

ACIP Recommends Clesrovimab for Infants Under 8 Months Without Maternal RSV Protection

In a significant move to protect infants from severe respiratory syncytial virus (RSV) disease, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend clesrovimab (Enflonsia), a newly FDA-approved monoclonal antibody, for all infants under 8 months who lack maternal RSV protection during their first RSV season. The committee also voted to include clesrovimab in the Vaccines for Children (VFC) program, ensuring no-cost access for eligible families. With strong efficacy, over 80% reduction in RSV-related hospitalizations, and a favorable safety profile, clesrovimab offers a simplified, single-dose option that could prevent tens of thousands of RSV-related healthcare visits and deaths annually, reinforcing its role as a vital tool in pediatric RSV prevention.

How Can Scientists and Investigators Find Funding Today?

At the ASM Microbe 2025 conference, Rodney E Rohde, PhD, highlighted growing concerns over federal research funding freezes and their potential impact on public health careers, particularly among students and early-career scientists. As a professor and chair at Texas State University, Rohde emphasized the need for creative alternatives to traditional funding sources, including private foundations, institutional grants, state-level opportunities, and partnerships with local organizations. While federal agencies like the NIH and NSF remain essential pillars of scientific advancement, Rohde stressed the importance of sustained engagement with these institutions to advocate for future investment. Despite current challenges, he remains hopeful that healthy competition for grants will continue to drive innovation and discovery in the life sciences.

Improving Quality of Life For Those With Recurrent C Difficile

 infection (rCDI) significantly diminishes patients' health-related quality of life (HRQoL), often causing anxiety, isolation, and fear of relapse. Paul Feuerstadt, MD, emphasizes the emotional toll of rCDI, likening it to post-traumatic stress, and highlights the transformative impact of fecal microbiota, live-jslm (Rebyota [RBL]), a non-antibiotic treatment approved by the FDA for over two years. A recent quality-of-life survey conducted by RBL’s manufacturer, Ferring Pharmaceuticals, found that patients who responded to RBL reported greater improvements in mental, physical, and social well-being than those on placebo. These gains were linked to beneficial shifts in gut microbiota and bile acid profiles, underscoring the therapy’s dual role in addressing both infection and overall patient wellness.

New Antifungal Drug Olorofim Shows Efficacy in Treating Resistant Fungal Infections

A novel antifungal drug, olorofim, has shown promising efficacy and safety in treating life-threatening invasive fungal infections (IFDs), particularly in patients with limited treatment options due to resistance. In a phase 2b trial involving over 200 patients infected with difficult-to-treat pathogens like azole-resistant 

, olorofim achieved a clinical response in nearly 60% of patients by day 42, with no resistance observed during treatment. John Rex, MD, FACP, chief medical officer at F2G, emphasized the drug’s targeted mechanism and oral formulation, noting its potential as a long-term option for high-risk fungal infections, while cautioning against future misuse in agriculture that could jeopardize its clinical effectiveness.

Antibody Levels Below Traditional Threshold Still Protect Against Hepatitis B in Vaccinated Children

 suggests that children vaccinated against hepatitis B remain protected even when their antibody levels fall below the traditional threshold of 10 mIU/mL, challenging the long-held assumption that such declines necessitate booster doses. Over a 5.4-year period, researchers followed 395 children born to HBV-infected mothers, one of the highest-risk groups, and found no cases of breakthrough infection, even among those with low or declining antibody levels. Notably, some children with reduced antibody levels experienced a natural immune boost without infection, likely due to HBV exposure, underscoring the strength of long-term immunity. While the study did not assess cellular immunity and booster administration wasn’t randomized, its findings may prompt reevaluation of current hepatitis B vaccination policies, potentially reducing unnecessary booster shots in similarly exposed populations.

This week, the ACIP recommends clesrovimab for RSV protection in infants under 8 months without maternal immunity, ASM Microbe talk urges for creative funding solutions amid federal freezes to sustain research and careers, and more.

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