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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

David Relman, MD, discusses the theoretically issues of the Mirror Life, how the scientific community could potentially research synthetic life with natural chirality, and how mirror molecules may be a way to extract beneficial research from the concept.    

Understanding the Serious Risks, Potential Benefits to the Mirror Life Concept 

For the uninitiated, the concept of "mirror life" is a hypothetical form of life that was first theorized by Louis Pasteur. This alternative life form has never been discovered in nature, although certain mirror-image components of molecular machinery have been synthesized in the laboratory and, in principle, entire mirror organisms could be created.

“All life on this planet makes use almost exclusively of just 1 of those 2 configurations. For example, all DNA is right-handed. All proteins are left-handed. But it turns out that it's possible to create the opposite left-handed DNA and right-handed proteins in the laboratory synthetically. And so in theory, one could create a living cell, a synthetic cell based on these opposite mirror-image molecules,” explains David Relman, MD, professor of medicine infectious diseases and a professor of microbiology and immunology at Stanford University.

In December of last year, Relman was part of a large group of scientists who warned the public in an article in 

 that the creation of mirror life could cause "unprecedented and irreversible harm" to human health and ecosystems worldwide.

“The possible benefits of creating mirror life are very few and limited, whereas the risks of building mirror life are quite substantial and potentially catastrophic, and that balance between possible catastrophic risk and very limited benefits clearly favors a decision not to go forward with what had been the plans of some scientists,” Relman said in an interview with 

Relman was a moderator on a panel who discussed this topic at this year’s ASM Microbe conference. The panel covered the concerns around this concept, the challenges of protecting the potential benefits of work toward the creation of natural chirality synthetic life while preventing the creation of mirror-image synthetic life, and discussed the role that microbiologists and other scientists might play in these discussions.

Trying to extract the potential benefits will be a difficult task, explains Relman.

“The challenge will be to protect the science that we believe is well worth pursuing, science that is likely to be quite beneficial and of minimal risk while still preventing this potentially catastrophic science,” Relman said. “Those two endeavors are somewhat related because there are important efforts underway to build synthetic natural chirality life that we think will lead to some very important biomedical products, insights, and potentially cures and therapeutics.”

One area within this concept that Relman is in favor of is mirror molecules.

“Mirror proteins have this unusual property of being almost totally resistant to being broken down by enzymes that we have on this planet that makes them potentially valuable drugs, when the problem is often that our drugs are broken down too quickly to be able to have an effective response in a patient,” Relman said. “There are pharmaceutical companies that are quite interested in mirror proteins or even mirror oligonucleotides as therapeutics. But as I say, we do not need to create mirror life in order to produce those mirror molecules."



In part 2 of the conversation, Relman talks about how scientists can play a role in public policy around mirror life and the potentially extreme serious consequences that could emerge from the concept. 

References
1. Mirror life. Wikipedia. Accessed August 2, 2025.


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

2. Adamala KP, Agashe D, Belkaid Y, et al

David Relman, MD, discusses the theoretical issues of "mirror life," how the scientific community could potentially research natural chirality synthetic life, and how mirror molecules may be a way to extract beneficial research from the concept.    

Conferences

Understanding the Serious Risks, Potential Benefits Around the Mirror Life Concept 

COVID-19 infections are rising across much of the United States, particularly in the South and Midwest, according to the Centers for Disease Control and Prevention (CDC). As key indicators such as wastewater viral levels, test positivity, and emergency department visits trend upward, health experts warn of a potential late-summer surge. This rise coincides with federal efforts to restrict access to updated booster vaccines, prompting concern from scientists and public health officials.

Despite changing federal guidance, recent data from a CDC interim report underscores the value of updated 2024-2025 COVID-19 vaccines. The report found that

Among adults 65 years and older, vaccine effectiveness (VE) was 45% to 46% against hospitalization for immunocompetent individuals and 40% for immunocompromised individuals.

Among adults 18 years and older, VE against emergency department or urgent care visits was 33% during the first 7 to 119 days after vaccination.

These results support the CDC and Advisory Committee on Immunization Practices recommendation that all individuals aged 6 months and older receive the 2024-2025 vaccine.

Nevertheless, the Trump administration's 2025 policy update has limited eligibility for updated boosters to those 65 years and older and individuals 12 years and older with certain health conditions, excluding most children and pregnant individuals from broad recommendations.

“If you’re vaccinated against COVID-19, you’re less likely to get infected,” said virologist Andrew Pekosz, PhD, of Johns Hopkins University. “But we haven’t gotten a lot of people vaccinated for the past few years, and with the current recommendations changing, it’s even less likely."

Sam Scarpino, PhD, a professor at Northeastern University, warned that variants with immune-escape properties are likely to drive another wave. “Whether it’s going to be large or small, I don’t think we could really say…but the vaccines are still providing some protection. It’s never too late to get the booster."

Experts expressed concern that narrowing access to boosters undermines efforts to reduce community transmission. “If you vaccinate broadly, you can reduce the spread of COVID-19 in the population,” said Pekosz.

Vaccination uptake remains low: only 23% of adults had received updated boosters as of April 2025. Among young children aged 6 months to 4 years, just 5.6% are vaccinated; for children 5 to 17 years old, about 15% are vaccinated, per CDC estimates.

COVID 19-related deaths remain significant, with 35,000 to 54,000 recorded since October 2024, and 149 deaths in the week ending June 28 alone. Long COVID affects approximately 5.3% of adults, though updated federal data has not been released this year.

Children continue to experience COVID-19 hospitalization rates consistent with past years, especially given low immunity due to low vaccination rates. “COVID cases are really occurring in children at a very high level right now,” Pekosz said. “It’s not nearly as dangerous in children as in adults, but it still causes a lot of hospitalizations."

Treatment Strategies for High-Risk Patients Evolve

Antivirals like nirmatrelvir-ritonavir remain effective and are not currently subject to usage restrictions by the CDC or US Food and Drug Administration, though a federal subsidy program is scheduled to end in December. “It’s not so much that the virus has become less dangerous,” said Pekosz. “It’s that we have immunity, so we fight off the virus more efficiently than we did early in the pandemic."

He added that prevention remains key: masking, improving ventilation, staying home when sick, and especially vaccination. “When the government doesn’t use the science to drive their decision making, you can see the confusion that it puts into the general public."

As concern grows over rising COVID-19 cases and low vaccine uptake, new data offers potential guidance for protecting one of the most at-risk groups: immunocompromised individuals. A phase 2 trial from Pfizer (EPIC-IC) found that extending the antiviral regimen of nirmatrelvir-ritonavir (Paxlovid) beyond the standard 5-day course significantly reduced rates of viral rebound, even though overall viral suppression remained similar across 5-, 10-, and 15-day treatment groups.

In the trial, viral rebound occurred in 17.3% of patients treated for 5 days, compared to just 2.1% and 2% in the 10- and 15-day groups, respectively. These findings suggest that longer treatment durations may improve outcomes for patients with prolonged infections, a group already at high risk of developing long COVID, viral resistance, and complications.

While the standard 5-day regimen remains appropriate for most, researchers say extended courses could offer additional protection for severely immunocompromised patients. Adverse effects were generally manageable across all groups, and only the 5-day cohort experienced COVID-related hospitalizations. Pfizer has launched a follow-up study (ASPIRE-IC) to further investigate optimal treatment duration.

These findings add to mounting evidence that sustained antiviral access and personalized care remain critical tools, particularly as many high-risk individuals face restricted vaccine eligibility and ongoing viral exposure.

Covid cases rising in US as officials plan to restrict booster vaccines. The Guardian. August 5, 2025. Accessed August 5, 2025. 

https://www.theguardian.com/world/2025/aug/05/us-covid-cases-rising

2. Link-Gelles R, Chickery S, Webber A, et al. Interim estimates of 2024-2025 COVID-19 vaccine effectiveness among adults aged ≥18 years - VISION and IVY Networks, September 2024-January 2025. 

. 2025;74(6):73-82. doi:10.15585/mmwr.mm7406a1

3. Weinstein E, Paredes R, Gardner A, et al. Extended nirmatrelvir-ritonavir treatment durations for immunocompromised patients with COVID-19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial. 

. Published online July 14, 2025. doi:10.1016/S1473-3099(25)00221-X

Low vaccine uptake, immunity gaps, and new antiviral data raise alarms ahead of a potential late-summer surge.

Rising COVID Cases and Narrowed Booster Access Spark Concern Among Experts

Clarametyx Biosciences announced it had received fast track and qualified infectious disease product (QIDP) designations from the FDA for the company’s investigational antibody therapy CMTX-101. The therapy is being studied to treat people with cystic fibrosis (CF) who are affected by chronic bacterial pulmonary infections, including nontuberculous mycobacterial (NTM) lung disease, non-CF bronchiectasis (NCFB), and chronic obstructive pulmonary disease (COPD).

“The receipt of both fast track and QIDP designations from the FDA underscores CMTX-101's potential as an innovative therapy for patients suffering from chronic respiratory conditions. We look forward to working even closer with FDA to expedite the approval of a new therapy for patients suffering from difficult-to-treat pulmonary conditions,” Clarametyx CEO David V. Richards said in a news release.

With this news and the company securing funding with its Series A financing from existing investors to support ongoing pipeline activities, Clarametyx is expanding its phase 2 study and aims to have full enrollment by the end of the year.

The company announced a positive interim analysis in June. The ongoing randomized, double-blind, placebo-controlled clinical trial is assessing CMTX-101 as an adjunctive therapy to standard of care antibiotics in people with CF, evaluating safety and tolerability, pharmacokinetics, immunogenicity, reduction of pulmonary 

 burden, and additional exploratory end points. 

An interim analysis of data from the first 21 participants enrolled met the prespecified criteria to continue the trial at both 5 and 30 mg/kg dose levels. Participants treated with CMTX-101 demonstrated a reduction in 

  based on prespecified statistical criteria and CMTX-101 was shown to be present in the sputum of all treated participants. Importantly, CMTX-101 was generally well tolerated, consistent with the findings reported in a prior clinical study, and no antidrug antibodies were detected.



Clarametyx Biosciences Initiates Phase 2a Trial for CMTX-101 in Cystic Fibrosis Patients

CMTX-101 is an investigational immune-enabling antibody therapy in development to address chronic respiratory disease exacerbation and lung function decline. The therapy is designed to precisely and rapidly destroy the universal underlying, proinflammatory structure of bacterial biofilms to undermine extracellular bacterial defenses and enable more effective antibiotic and immune intervention. Because the target is universally present across bacteria, the approach can treat a range of bacterial infections and pathogen types. 

The goal of treatment is to dramatically improve the effectiveness of innate immune system effectors and antibiotic therapies, thereby addressing inflammation pathways driven by the biofilm state.




References
1. Clarametyx Biosciences announces FDA grant of fast track and qualified infectious disease product designations for CMTX-101. News release. Clarametyx. August 4, 2025. Accessed August 5, 2025. 

https://www.businesswire.com/news/home/20250804750253/en/Clarametyx-Biosciences-Announces-FDA-Grant-of-Fast-Track-and-Qualified-Infectious-Disease-Product-Designations-for-CMTX-101


2. Clarametyx Biosciences announces positive interim analysis in phase 2a study evaluating CMTX-101 for infections associated with cystic fibrosis. News release. Clarametyx. June 16, 2025. Accessed August 5, 2025.
https://clarametyx.com/positive-interim-analysis-in-phase-2a-study/

Clarametyx Biosciences said its investigational antibody therapy, CMTX-101, which is in a phase 1b/2a study, remains on track for full trial enrollment by the end of 2025. 

FDA Fast Tracks Antibody Therapy for Pulmonary Infections Including Cystic Fibrosis

Erica Kaufman West, MD, FIDSA, highlighted in the Infectious Diseases Society of America’s (IDSA) Science Speaks blog that despite updated universal screening guidelines for 

 during pregnancy, testing rates remain far below recommended targets. West points to the ongoing opioid epidemic, which has fueled a rise in HCV infections among younger individuals, including pregnant women, as a driving force behind this growing public health concern.¹

Since the 1990s, the opioid epidemic has driven a surge in HCV infections, increasingly affecting younger populations, including women of childbearing age. Historically, HCV was mostly detected in baby boomers, but now, new infections are rising among pregnant individuals, raising concerns for mother-to-child transmission.²

In response, major public health organizations have revised screening recommendations. The Centers for Disease Control and Prevention updated guidelines in 2020 to recommend universal HCV screening for all pregnant individuals during each pregnancy, extending beyond the prior risk-based approach. The American College of Obstetricians and Gynecologists followed suit, issuing a practice advisory in May 2021 endorsing HCV screening during the first prenatal blood assessment in every pregnancy.³ Similarly, the Society for Maternal-Fetal Medicine recommends universal antibody testing for HCV in all pregnant patients.⁴

 earlier this year examined HCV screening trends from 2014 through 2022 in over 115 million patients across 68 US health care organizations.¹ Their interrupted time series analysis compared screening rates among pregnant vs nonpregnant women before (2014-2019) and after (July 2020-December 2022) the guideline update.⁵

Among pregnant women, screening rates more than doubled prior to the 2020 guideline change, from 52 to 117 tests per 1000 person-years.

Post-guideline, rates further increased from 141 to 253 tests per 1000 person-years.

By the end of 2022, only 38.73% of pregnant women were tested at least once for HCV.

In contrast, HIV screening rates in pregnancy remain over 90%, highlighting the gap in HCV testing uptake.

Screening among nonpregnant women increased modestly, from 16 to 24 tests before the guideline change and 29 to 37 afterward per 1000 person-years.

The study authors emphasize that while progress is evident, testing remains suboptimal. The perinatal period represents a critical health care touchpoint that should be leveraged for universal HCV diagnosis and linkage to care.⁵

The Challenge of Treatment During Pregnancy

Currently, no HCV treatment is approved by the US Food and Drug Administration for use during pregnancy, although ongoing research explores the safety and efficacy of direct-acting antiviral therapies in this population. The American Association for the Study of Liver Diseases, Infectious Diseases Society of America, and European Association for the Study of the Liver support considering treatment in pregnancy under clinical trial settings and recommend reporting such cases to the TiP-HepC Registry.⁶

In the meantime, obstetric providers are urged to connect pregnant individuals who test positive with HCV care postpartum to initiate treatment after delivery and breastfeeding. Pediatric providers must be informed of maternal HCV status to ensure appropriate infant testing and follow-up.⁶

Hepatitis C infection can remain asymptomatic for years, with approximately 75% to 85% of infected individuals unaware of their status. Vertical transmission occurs in about 6% of infants born to infected mothers and is associated with adverse fetal outcomes including low birthweight and fetal growth restriction.²⁴

The high rates of HIV screening during pregnancy demonstrate that universal infectious disease screening in this setting is achievable. Stakeholders agree that innovative strategies and systems-level changes are urgently needed to improve HCV screening rates and ensure timely treatment, ultimately advancing toward the national goal of hepatitis C elimination.⁵

West E. HCV screening in pregnancy: we must do better. IDSA Science Speaks blog. July 22, 2025. Accessed August 6, 2025. https://www.idsociety.org/science-speaks-blog/2025/hcv-screening-in-pregnancy-we-must-do-better/

2. Hepatitis C virus infection. Centers for Disease Control and Prevention. Updated January 2025. Accessed August 6, 2025. 

https://www.cdc.gov/hepatitis/hcv/index.htm

3. American College of Obstetricians and Gynecologists. Practice advisory: hepatitis C screening in pregnancy. May 2021. Accessed August 6, 2025. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/05/hepatitis-c-screening-in-pregnancy

4. Dotters-Katz SK, Kuller JA, Hughes BL; Society for Maternal-Fetal Medicine. Consult series #56: hepatitis C in pregnancy. Society for Maternal-Fetal Medicine. 2021. Accessed August 6, 2025. https://publications.smfm.org/publications/577-society-for-maternal-fetal-medicine-consult-series-56/

5. Singh RP, Biondi B, Gordon SH, Linas BP, Epstein RL. Hepatitis C virus screening in pregnant and nonpregnant women after universal screening guidelines. 

. 2025;333(15):1356-1358. doi:10.1001/jama.2024.28774

6. American Association for the Study of Liver Diseases; Infectious Diseases Society of America; European Association for the Study of the Liver. Recommendations for Hepatitis C Treatment in Pregnancy. Accessed August 6, 2025. https://www.aasld.org/publications/hepatitis-c-treatment-pregnancy

Despite updated guidelines for universal hepatitis C virus screening in pregnancy, testing rates remain well below targets, missing chances to prevent perinatal transmission.


Universal Hepatitis C Screening in Pregnancy: Progress Made, But Challenges Remain

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 around 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 (NIH), the findings showed similar 30-day mortality rates but higher resistance emergence in the ceftolozane-tazobactam group (38% vs 25%). Tamma was the senior investigator on this trial.

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



Yoav Golan, MD

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