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Lawrence is a member of the Peggy Lillis Foundation's board of directors.

Kenneth Lawrence, PharmD, discusses the global problem and the need for a layered, multifaceted approach to antimicrobial resistance (AMR) and some of the ongoing inroads and progress being made to address the medical issue.

Antimicrobial Resistance: Cause for Concern and Optimism?

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 CDC has confirmed the first severe human case of avian influenza (H5N1) in the US, involving a patient from Louisiana with a history of exposure to backyard poultry. This follows global patterns of severe illness associated with poultry contact. 

The patient is the first such case in the US to be severe enough for the person to be hospitalized. Thus far, all previous patients in confirmed cases have had mild symptoms not requiring hospitalization. The case was confirmed by the CDC on December 13, and the Louisiana Department of Health has not released additional information about the patient, citing privacy concerns.

The patient’s infection was identified as the D11 genotype of the virus, which is commonly found in wild birds and has previously been linked to severe cases in regions like Canada and Washington state. Unlike the B313 strain, which has caused milder symptoms in dairy workers exposed to infected cattle, the D11 genotype appears to be more serious.

Genetic testing is ongoing to assess whether any mutations indicate increased danger or potential human-to-human spread, but no other related cases have been reported so far. The CDC continues to assess the risk as low to the public. It is important to note that although the D11 genotype appears to be more virulent, there has been no person-to-person transmission of the virus detected.

 recently spoke to NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Director Jeanne Marrazzo, MD, MPH, about mutations and human-top human transmission.

“The virus would still likely need to acquire additional mutations to acquire the ability to spread effectively among humans,” Marrazzo said.

With this first severe case, the US now has 61 confirmed human cases of H5N1. Last week there were 58 cases, with the overwhelming majority of cases confirmed in California. Just yesterday, California Governor Gavin Newsom declared 

“This proclamation is a targeted action to ensure government agencies have the resources and flexibility they need to respond quickly to this outbreak. Building on California’s testing and monitoring system—the largest in the nation—we are committed to further protecting public health, supporting our agriculture industry, and ensuring that Californians have access to accurate, up-to-date information. While the risk to the public remains low, we will continue to take all necessary steps to prevent the spread of this virus,” Newsom said in a statement.

In California, there have been 34 human exposure incidents in the state overall and all but 1 of the cases have been linked to commercial agriculture and related operations. The one outstanding case was classified as having an unknown source. These figures reflect the overall exposure risk in the state tied to agricultural and animal operations.

The proclamation follows the detection of additional bird flu cases in dairy cows. While the risk to the public remains low, the declaration aims to provide state and local agencies with the resources and flexibility needed to respond swiftly and effectively. 

For the Louisiana case, it has been determined that the patient had exposure to sick and dead birds in backyard flocks. This is the first case of avian infleunza in the US that has been linked to exposure to a backyard flock. A sporadic case of severe H5N1 bird flu illness in a person is not unexpected; avian influenza infection has previously been associated with severe human illness in other countries during 2024 and prior years, including illness resulting in death.

Reference
1. CDC Confirms First Severe Case of H5N1 Bird Flu in the United States. CDC press release. December 18, 2024. Accessed December 19, 2024.


https://www.cdc.gov/media/releases/2024/m1218-h5n1-flu.html


2. Governor Newsom takes proactive action to strengthen robust state response to Bird Flu. Published December 18, 2024. Accessed December 18, 2024. 

https://www.gov.ca.gov/2024/12/18/governor-newsom-takes-proactive-action-to-strengthen-robust-state-response-to-bird-flu/


3.Avian Influenza (Bird Flu). H5 Bird Flu: Current Situation. CDC. Updated December 17, 2024. Accessed December 18, 2024. 

https://www.cdc.gov/flu/avianflu/index.htm

The Centers for Disease Control and Prevention (CDC) has reported a case in Louisiana where the patient is hospitalized due to the virus, and had a history of exposure to backyard poultry.

The First Severe Case of Avian Influenza Confirmed in the United States

the panel weighs in on treatments not specifically indicated for COVID-19 treatment, including metformin, and concerns around using medications in this way.

COVID-19 Roundtable: Considering Off Label COVID Therapies

During the earliest stages of the pandemic, and before the development of antivirals and other therapies, clinicians were struggling to find ways to treat their patients. As providers began to use off-label treatments, small studies began to surface around various therapies including hydroxychloroquine, the antimalarial therapy, and the antibiotic, azithromycin. One published paper found these 2 therapies used in combination could help reduce viral loads.

And while clinicians quickly realized these therapies were not reducing symptoms or mortality, both disinformation and misinformation was prevalent enough and making the therapies out to be wonder drugs. These therapies’ efficacy for COVID-19 treatment were debated on social media for way too long.

Just this week, that aforementioned paper about hydroxychloroquine and azithromycin was finally retracted.The paper had been published in the 

International Journal of Antimicrobial Agents

 back in 2020, and the lead author was Philippe Gautret of the Hospital Institute of Marseille Mediterranean Infection. In the paper, it was claimed that hydroxychloroquine was able to reduce virus loads in COVID-19 patients, and that used in combination with azithromycin, was even more effective.

This year, there has been some studies looking at metformin as an off-label treatment for COVID-19. However, with limited data showing efficacy and potential adverse effects, our roundtable panel believes it is better to prescribe FDA approved therapies.

“I don't think there's an overwhelming amount of data that would support it. With metformin, there were two studies together that pretty much showed it wasn't effective,” said Michael Curulewski, PharmD, BCPS, BCIDP, BCGP infectious diseases and antimicrobial stewardship pharmacist, Endeavor health, Northwest Community Hospital. “One thing to keep in mind is anytime that we use an off-label therapy or a therapy that's not supported by a large amount of data, [or even] the safety profile is a major one for me—because a lot of the medications are not benign. Metformin, for example, we have to watch out for patients who have renal dysfunction, IV contrast exposure, and drug-drug interactions. So, without that data to support it, I would say I don't routinely endorse or recommend off-label therapies.”



This is episode 3 of our 4-part series. Check back for the last episode next week.

Reference
1. O’ Grady C. Infamous paper that popularized unproven COVID-19 treatment finally retracted. 

December 17, 2024. Accessed December 17, 2024. https://www.science.org/content/article/infamous-paper-popularized-unproven-covid-19-treatment-finally-retracted

In this week's episode, the panel weighs in on treatments not specifically indicated for COVID-19 treatment, including metformin, and concerns around using medications in this way.



Canonical

COVID-19 Roundtable: Should Clinicians Consider Off Label COVID Therapies?

Antibiotic- or antimicrobial-resistant (AMR)

 bacteria cause highly difficult to treat infections, draining both money and hospital resources. AMR develops after systemically treating bacterial infections with various unnecessary 

. Bacterial infections are usually treated dynamically, with antibiotics rapidly switched mid-treatment.

, sought to understand the effects of frequently changing antibiotic therapies in individual patients. “Clinicians often try a certain antibiotic for a defined time and then switch to a different antibiotic,” said study author Gregory Priebe, MD, “but how switching therapies affects antibiotic resistance is unknown.”

To track the changes and frequencies of AMR mutations over time, the investigators used a new technique they call resistance-targeted deep amplicon sequencing (RETRA-Seq). RETRA-Seq combines whole-genome sequencing with deep-sequencing. “RETRA-Seq tests the bacterial population as a whole, so it can detect these rare antibiotic-resistant bacteria with much higher sensitivity than routine clinical methods,” said Alex McAdam, MD, PhD, a co-author of the study.

samples collected serially from 7 patients. The sample donors were hospitalized at Boston Children’s and required mechanical ventilation at the onset of respiratory infection. Testing commenced at infection onset and continued for 4-11 days, during the course of antibiotic treatments. From the patients’ sputum samples, the investigators sequenced 420 cultured bacterial colonies.

The investigators found that small-scale antibiotic resistance waxed and waned as treatment therapies were changed. 

gene mutations changed rapidly, with AMR mutations emerging after antibiotic treatment began and disappearing within days of switching to another treatment.

The RETRA-Seq method revealed rare resistance mutations not previously detectable by clinically administered culture-based gene sequencing. The investigators found antimicrobial resistance could increase nearly 40-fold in 5-12 days in response to changing the patients’ antibiotics regimen.

Our results suggest that antibiotic cycling might be more effective at the level of individual patients,” said Priebe. “We are looking to use genomic surveillance to inform initial antibiotic therapy — both the type of antibiotic and the timing — and then to inform switches in antibiotic as the frequencies of antibiotic resistance mutations change.”

This study, and the RETRA-Seq technique, may pave the way for choosing an antibiotics course that will not drive antimicrobial-resistant gene mutations in dangerous bacterial infections. Such research is vital to prevent the growing threat of antibiotic-resistant bacteria and bolster 

Using real-time genetic surveillance, investigators found bacterial infections rapidly develop resistance to antibiotics, only to have these gene mutations disappear within a few days of switching to a different treatment.

Effects of Switching Antibiotics Mid-Treatment on Antimicrobial Resistance

In our latest roundtable series, we cover different therapies around COVID-19 treatment and prevention. Clinicians offer insights on antivirals and 

COVID-19 Therapy Roundtable: Defining the Virus Today and Treatment Options   

we are continuing our ongoing series of roundtables where we gather a group of clinicians together to talk about specific infectious disease topics. During these discussions, they offer approaches to clinical management as it relates to various diseases and infections.

In this first roundtable episode, the panel touched upon what COVID-19 is at the end of 2024, offered insights on some of the FDA approved antivirals, and the limited treatment options for pediatric patients.

The Centers for Disease Control and Prevention (CDC) views COVID-19 as an endemic virus.

 As it circulates in perpetuity, we will continue to witness ebbs and flows in its prevalence. And certainly during the holiday season, respiratory virus incidence rates can increase due to a number of factors including families and friends gathering together, a greater frequency of travel, and people are in closed environments because of the winter climate.

Clinicians, public health officials, and interested stakeholders will always stress the importance of vaccination as the best way to prevent or reduce the severity of COVID-19. However, people will continue to get infected, especially as the statistics for vaccination are down.

 report published a few weeks ago offered insights on the vaccination statistics so far into the respiratory virus season. “As of November 9, 2024, cumulative estimated coverage with 2024–2025 influenza and COVID-19 vaccines among adults aged ≥18 years was 34.7% and 17.9%, respectively. Estimated RSV vaccination coverage was 39.7% among adults aged ≥75 years and 31.6% among those aged 60–74 years at increased risk,” the authors wrote.

Our panel of clinicians for this roundtable series includes:

Tina Tan, MD, professor of Pediatrics, Feinberg School of Medicine, Northwestern University

Scott Roberts, MD, associate medical director of Infection Prevention, Yale School of Medicine

James Wilson, DO, FACP, FAWM, CTropMed, critical care physician in private practice

Michael Curulewski, PharmD, BCPS, BCIDP, BCGP infectious diseases and antimicrobial stewardship pharmacist, Endeavor health, Northwest Community Hospital

We will continue our conversation next week, so check back then for the latest episode.



References
1.Stein R. Is COVID endemic yet? Yep, says the CDC. Here's what that means. NPR. August 9, 2024. Accessed December 4, 2024.


https://www.npr.org/sections/shots-health-news/2024/08/09/nx-s1-5060398/covid-endemic-cdc-summer-surge


2.Kriss JL, Black CL, Razzaghi H, et al. Influenza, COVID-19, and Respiratory Syncytial Virus Vaccination Coverage Among Adults — United States, Fall 2024. MMWR Morb Mortal Wkly Rep 2024;73:1044–1051. DOI: 

In our latest roundtable series, we discuss COVID-19 treatment management and prevention 4 years after the start of the pandemic.

COVID-19 Therapy Roundtable: What is the Virus Today, Treatment Options, and Addressing the Pediatric Population

 has increased significantly in rural areas across the US. One study pointed out that the number of cases had more than double in rural areas vs urban areas.

 This increase has also been linked to injection drug use with 75% of the individuals followed in the study having reported engaged in this activity. Much of these developments stem from the prescription opioid crisis with people possibly starting with opioids and progressing to illicit drug use.

Additionally, getting people in rural areas with hepatitis C into the continuum of care can be difficult, especially with limited, nearby medical institutions and programs or having a network of peers who might also be affected with the same affliction.

With these inherent challenges, a new study published recently in the journal,  

 demonstrated the success of getting people who use drugs into the continuum of care for HCV through a community-based peer support telemedicine approach. The study evaluated enlisting people with a lived experience of substance abuse and having them meet others who use drugs, try to get them tested for the blood borne disease and into treatment via telehealth or referral to a physical clinic.

“Rural people who use drugs may be more likely to trust their peers, even when they don’t trust health care providers,” lead author Andrew Seaman, MD, an associate professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine, said. 

Peers with a shared drug use experience recruited other people who use drugs (PWUD) in 7 rural counties in Oregon where there were higher incidence rates of hepatitis C and opioid overdoses. 

Study criteria included individuals who were at least 18 years of age or older, lived within the study area, had injected drugs or used non-prescribed opioids within 90 days of screening, and had a detectable HCV. For nearly 2 ½ years, from July 17, 2020 to December 12, 2022, 774 people were screened, with 227 having detectable HCV RNA, and 203 participants were randomized with 100 of the participants assigned to peer-assisted telemedicine hepatitis C treatment (TeleHCV) and 103 participants were placed into the peer-assisted referral to local providers enhanced usual care (EUC).

“Eighty-five percent (85/100) of participants randomized to the TeleHCV arm initiated treatment compared to 13% (13/103) of EUC (RR = 6.70, 95% CI 4.00, 11.30, 

In addition, viral clearance or functional cure, was achieved in 63% of people in the TeleHCV group vs just 16%in the EUC group.

“This study shows the importance of empowering trusted peers to support the health of people who use drugs, and the crucial role telemedicine can play to expand hepatitis C treatment to rural communities...Hepatitis C causes liver cancer, loss of productivity, diabetes and all kinds of complications that cost lives and money. And it’s transmissible, so every time a patient is cured, we also prevent multiple transmissions to other people, Seaman said.”


References
1. Suryaprasad AG, White JZ, Xu F, et al. 

Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012

. 2014;59(10):1411-1419. doi:10.1093/cid/ciu643
2. Robinson E. Telehealth plus local peer support boosts treatment success for hepatitis C in rural patients. Oregon Health & Science University News. November 27, 2024. Accessed December 17, 2024. 

https://news.ohsu.edu/2024/11/27/telehealth-significantly-boosts-treatment-success-for-hepatitis-c-in-rural-patients


3. Seaman A, Cook R, Leichtling G, et al. Peer-assisted telemedicine for hepatitis C in people who use drugs: A randomized controlled trial. 

. Published online November 27, 2024. doi:10.1093/cid/ciae520

A study found deploying peers with lived experience in illicit drug use increased the rate of people diagnosed, treated, and cured of the disease.

Kenneth Lawrence, PharmD

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