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As current antibiotics become less effective due to bacterial resistance, there is high demand for new and effective therapies with both IV and oral formulations.

Antibiotic Resistance: Challenges and Opportunities for Treating Serious Bacterial Skin Infections

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

This is the second in a series looking at the intersection of government and public health. 

Will Trump Administration’s Funding Pauses, Withdrawal from WHO Hamper Public Health? 

On January 20, the Trump Administration issued an executive order announcing its withdrawal from the World Health Organization (WHO).

The order stated it was, “due to the organization’s mishandling of the COVID-19 pandemic that arose out of Wuhan, China, and other global health crises, its failure to adopt urgently needed reforms, and its inability to demonstrate independence from the inappropriate political influence of WHO member states. In addition, the WHO continues to demand unfairly onerous payments from the United States, far out of proportion with other countries’ assessed payments. China, with a population of 1.4 billion, has 300 percent of the population of the United States, yet contributes nearly 90 percent less to the WHO."

“I think we're going to find out more about what it means going forward,” said Jason Gallagher, FCCP, FIDP, FIDSA, BCPS, clinical professor at Temple University School of Pharmacy and clinical pharmacy specialist in Infectious Diseases at Temple University Hospital, of the WHO withdrawal. “I think as much as anything else, it's a signal that is concerning for the degree to which the United States wants to engage in the rest of the world, and related to public health.”

“Through membership in the WHO the US gets influence on health policy around the world. And I don't think that's the kind of thing you want to give up. Within the more tangible benefits, WHO is doing epidemiology work and detection of outbreaks. That seems to be where some of the disagreement with them has been at least from a gut opinion perspective.”

And while it was believed to be a gradual withdrawal with WHO, within a week, a memo came from the Centers for Disease Control and Prevention’s (CDC), Deputy Director for Global Health John Nkengasong, PhD, which was written to senior leaders at the agency telling employees that work with the WHO must immediately stop and to “await further guidance.” Congress will need to approve withdrawing from the WHO, and the country has to provide a 1-year notice.

Now is Not the Time for Funding Pauses, Cutting Ties With Health Organizations

Within the administration’s flurry of executive orders, there was a pause put on federal communications. This included not publishing the CDC’s 

Morbidity and Mortality Weekly Report (MMWR)

 last Thursday. It is a significant public health publication. This pause on not publishing this report was the first time in decades. This report has been publishing since the 1950s. 

“This is a premier health publication that everybody reads…multiple times a year you take a peek at that one because people are talking about something that has been described in 

,” Gallagher said. "It's used for other publications as well; recommendations, guidelines, and so forth that can go in other places, but it really has been a stalwart of US public health and our information network about health for decades."

 was not published yesterday—marking 2 weeks in a row—and it remains to be seen, if and when, this will come back.

In a January 27 memo sent by Matthew Vaeth, acting director, Office of Management and Budget (OMB), to the heads of executive departments and agencies, a pause was placed on all funding, including research grants.

The memo stated, “to the extent permissible under applicable law, federal agencies must temporarily pause all activities related to obligation or disbursement of all federal financial assistance, and other relevant agency activities that may be implicated by the executive orders, including, but not limited to, financial assistance for foreign aid, nongovernmental organizations, DEI, woke gender ideology, and the green new deal.”

The memo also stated this was a temporary pause and gives the administration time to review agency programs and “determine the best uses of the funding for those programs consistent with the law and the President’s priorities.”

Later, the OMB rescinded the memo, but the White House press secretary said other freezes tied to executive orders issued by Trump remained in effect. This has led to more confusion, uncertainty, and delays including research.

“Money not going into research funds means money not going into clinical trials, which are not going into discovering therapies that are ultimately going into patients. And with the sort of wide pauses and suspension of some of the work of our federal health agencies in NIH, CDC, and FDA—that's what I think of more than anything else,” Gallagher said. He notes a large portion of the university funding for research comes from those aforementioned government agencies.

Much remains to be seen how this will all play out. The hearings for Robert F. Kennedy Jr for the Health and Human Services Secretary position were this week and a vote for his confirmation has not taken place yet. If he does become secretary, this could also have long term effects on public health policy including vaccines. 

“I think most pauses will be lifted at some point, and what comes off on the other side of that is something we don't know. It could be stipulations, and what can be researched,” Gallagher said.




References
1.Withdrawing the United States From the World Health Organization. White House executive order. The White House. January 20, 2025. Accessed January 31, 2025. https://www.whitehouse.gov/presidential-actions/2025/01/withdrawing-the-united-states-from-the-worldhealth-organization/
2.CDC ordered to stop working with WHO immediately, upending expectations of an extended withdrawal. WHYY. January 27, 2025. Accessed January 31, 2025. 

https://whyy.org/articles/trump-cdc-who-public-health/


3. Trump Spending Freezes Sow Confusion Among Researchers. AIP. January 30, 2025. Accessed January 31, 2025.
https://ww2.aip.org/fyi/trump-spending-freezes-sow-confusion-among-researchers

This is the second in a series looking at the intersection of government and public health. In this segment, Contagion Editor-in-Chief Jason Gallagher, FCCP, FIDP, FIDSA, BCPS, discusses the WHO pullout, and the pauses on federal communication and research grants. 

The CHIKV VLP vaccine is a single-dose vaccine aimed at preventing chikungunya virus, which is transmitted by mosquitoes and can cause fever and debilitating joint pain. If approved, this will be the first and only VLP-based vaccine for chikungunya available in the US The vaccine is being developed for adults aged 12 and older.

ABCWY is a vaccine for invasive meningococcal disease, protecting against multiple strains of 

. It is designed for primary care and pediatric populations to prevent serious, potentially fatal infections like meningitis and septicemia caused by this bacteria.

MenQuadfi is a vaccine for the prevention of meningococcal disease in pediatric populations. It targets multiple strains of 

, the bacteria responsible for meningitis and other severe diseases. The vaccine is intended to help protect children from these life-threatening infections.

Gepotidacin is an antibiotic for the treatment of uncomplicated urinary tract infections (UTIs) in adult women. It offers a novel mechanism of action and represents a potential new treatment option, especially in cases where resistance to standard antibiotics is an issue.

Tesamorelin F8 is a growth hormone-releasing factor used to reduce excess abdominal fat in adults living with HIV and lipodystrophy. After receiving a Complete Response Letter (CRL) in January 2024 due to manufacturing concerns, Theratechnologies resubmitted the sBLA for review in late 2024, addressing issues related to chemistry, manufacturing, and controls.

The Novavax COVID-19 vaccine is a protein-based vaccine that has received Emergency Use Authorization (EUA) and is now seeking full approval for use in preventing COVID-19 infections. It offers an alternative to mRNA-based vaccines and is aimed at individuals who prefer a more traditional vaccine platform.

Clesrovimab is a monoclonal antibody aimed at protecting infants from RSV, has been accepted by the FDA. If approved, it will be the first single-dose immunization for infants, regardless of weight, offering protection throughout their first RSV season.

Zoliflodacin is an antibiotic being developed to treat gonorrhea, particularly against strains resistant to other antibiotics. It is a potential new option for treating this sexually transmitted infection, which has become increasingly difficult to treat due to antimicrobial resistance.

1. Bavarian Nordic. Bavarian Nordic announces FDA acceptance and priority review of the BLA for its chikungunya vaccine. PDUFA target action date of February 14, 2025. August 13, 2024. Accessed January 28, 2025. 

https://www.bavarian-nordic.com/investor/news/news.aspx?news=6967

2. GSK. GSK’s 5-in-1 meningococcal ABCWY vaccine candidate accepted for regulatory review by US FDA. Issued April 16, 2024. Published in London, UK. Accessed January 28, 2025. 

https://www.gsk.com/en-gb/media/press-releases/gsk-s-5-in-1-meningococcal-abcwy-vaccine-candidate-accepted-for-regulatory-review-by-us-fda/

3. Theratechnologies. Theratechnologies submits updated tesamorelin F8 formulation sBLA for FDA review. 

. November 26, 2024. Accessed January 27, 2025. 

https://www.theratech.com/news-releases/news-release-details/theratechnologies-submits-updated-tesamorelin-f8-formulation

4. GSK. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. October 16, 2024. Accessed January 28, 2025. 

https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections-in-female-adults-and-adolescents/

5. Theratechnologies Inc. Theratechnologies receives March 2025 PDUFA goal date for updated tesamorelin F8 formulation sBLA. December 10, 2024. Accessed January 28, 2025. 

https://www.theratech.com/news-releases/news-release-details/theratechnologies-receives-march-2025-pdufa-goal-date-update

6. Novavax. Novavax continues to partner with the U.S. FDA on review of 2024-2025 formula COVID-19 vaccine. Updated August 23, 2024. Accessed January 28, 2025. 

https://ir.novavax.com/press-releases/Novavax-Continues-to-Work-with-the-US-FDA-on-Authorization-of-2024-2025-Formula-COVID-19-Vaccine

7. GARDP. Request for Proposal for Managed Access Program for Zoliflodacin. Closing date: November 20, 2023. Accessed January 28, 2025. 

https://gardp.org/rfp/gardp-request-for-proposal-for-managed-access-program-for-zoliflodacin/

8. Merck. Merck announces FDA acceptance of Biologics License Application for clesrovimab, an investigational long-acting monoclonal antibody designed to protect infants from RSV disease during their first RSV season. 

. December 17, 2024. Accessed January 27, 2025. 

https://www.merck.com/news/merck-announces-fda-acceptance-of-biologics-license-application-for-clesrovimab-an-investigational-long-acting-monoclonal-antibody-designed-to-protect-infants-from-rsv-disease-during-their-first-rsv/

Vaccines and treatments are up for approval in early to mid-2025, including a chikungunya vaccine, a meningococcal vaccine, a monoclonal antibody for RSV, and more.





FDA Decisions to Watch Q1-Q2: Infectious Disease

David W. Denning outlines the "95-95 by 2025" initiative, aiming to diagnose and treat 95% of serious fungal infections globally by 2025, with a focus on improving access in underserved regions.

Fungal Infections: Invisible Until It’s Too Late

In 2015, fungal infections affected over 1 billion people globally each year, leading to an estimated 11.5 million life-threatening infections and more than 1.5 million deaths annually. Despite their significant impact, fungal diseases have historically been under-recognized and underfunded in global health efforts. In response, the Global Action Fund for Fungal Infections (GAFFI) launched a global initiative called "95-95 by 2025," which aims to diagnose and treat 95% of individuals with serious fungal infections by the end of 2025.

David W Denning, FRCP, FRCPath, FMedSci, professor of infectious diseases and global health at the University of Manchester, played a key role in developing GAFFI’s initiatives. Denning, also former chief executive of GAFFI, discussed the challenges of diagnosing and treating fungal infections and the goals of the 95-95 by 2025 initiative.

“We convened a meeting alongside one of the International AIDS meetings in Seattle in 2015 with about 60-70 people, including people from all over the world,” Denning said. “Some from Africa, South America, Asia, as well as people from the WHO and other major funding agencies to address the problem of how we're going to stop people dying of fungal disease. One of the problems with fungal disease is that it’s fairly invisible until it’s too late. You have to start looking for it in at-risk patients. So, examples of patients with AIDS, patients who have a transplant, patients with really complicated lung disease, patients with leukemia, lymphoma, that sort of group of patients."

Denning highlighted the lack of diagnostic infrastructure in many regions, particularly in Sub-Saharan Africa and Asia. He noted, “We learned that many countries, particularly in Sub-Saharan Africa, but also in many parts of Asia, don’t have a diagnostic service for fungal disease, and many of them don’t have any of the modern treatments for fungal disease. So, we ended up writing a roadmap that included a very basic summary of how many infections there might be in the world with these problems, and also the approaches, the diagnostics, and the treatments that are relevant to that."

Denning explained their goal, “Our aspiration 10 years ago now was that 95% of the world's population would have access to these diagnostics, and 95% would have access to the relevant anti-fungal therapies, particularly the generic anti-fungal therapies that are less expensive than the more recently issued ones."

Denning discussed the barriers to achieving this goal, including drug approval delays and the lack of resources in many countries. Denning explained, “For example, in South Africa, 

 was on the roster for approval for five years before they finally approved it, and yet it’s a core drug for fungal meningitis in AIDS. As you know, South Africa has the largest population of HIV patients per capita in the world.”

Denning noted that these delays are just one example of the challenges in ensuring access to affordable treatments. He said, “There are lots of different tests. There's lots of different lab approaches to handling those tests, and the registration processes for drugs are complicated in many countries.”

Denning discussed the progress made in countries like Guatemala, where GAFFI helped fund a project in 13 centers across the country. Denning described the process, “In Guatemala, we funded a small demonstration project and helped run it with about 13 centers across the country looking after patients with HIV and AIDS. We provided the wherewithal for them to run a rapid diagnostic service for two important fungal infections which are common: histoplasmosis and cryptococcal meningitis, in tandem with diagnostics for TB, which is also common there.”

The program successfully improved diagnostic accuracy, reduced misdiagnosis of tuberculosis as fungal infections, and ultimately led to a decrease in mortality. Denning shared, “We diagnosed many fungal infections, we diagnosed fewer TB infections, and that was because they were misdiagnosed as TB when actually they were a fungus. The overall mortality from these late-stage patients went down by 8% in basically two and a half years. And that’s a really big change.”

Denning expressed hope that similar programs could be replicated in other regions facing similar challenges, “We’d like to reproduce that other places. The idea here was to show that if you applied these diagnostics, and you provided the results quickly, and you trained the clinicians in parallel, you could really make a difference.”

Stay tuned for the next part of our conversation where we dive deeper into the initiative.

1. Denning DW. The ambitious '95-95 by 2025' roadmap for the diagnosis and management of fungal diseases. Thorax. 2015;70(7):613-614. doi:10.1136/thoraxjnl-2015-207305

2. Gaffi. IMPROVING OUTCOMES FOR PATIENTS WITH FUNGAL INFECTIONS ACROSS THE WORLD A ROAD MAP FOR THE NEXT DECADE. February 2025. Accessed January 20, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://gaffi.org/wp-content/uploads/GAFFI_Road_Map_interactive-final0415.pdf

David W Denning, FRCP, FRCPath, FMedSci, outlines the "95-95 by 2025" initiative to diagnose and treat 95% of serious fungal infections globally by 2025, focused on improving access in underserved regions.





Obesity is a worldwide epidemic and widespread in the US, affecting over one third of the population. According to the Centers for Disease Control and Prevention (CDC), all US states have an obesity prevalence that exceeds 20% and obesity disproportionately affects certain geographic, socioeconomic, ethnic, and racial groups.

 Obesity is an independent risk factor for various types of infections as well as poorer infection-associated clinical outcomes.

Obesity has significant effects on the pharmacokinetics (PK) of various anti-infective drugs, including antifungals, with two of the most important being volume of distribution (Vd) and clearance. Vd generally increases with obesity as a result of increased adipose and lean tissue mass, particularly for lipophilic and highly protein bound drugs. This increased Vd may necessitate higher individual doses and, in particular, loading doses. Additionally, wider variability may be seen in overall exposure in obese patients for drugs dosed by weight, increasing risk of both over- and underdosing. Clearance may be increased in obese patients due to increased renal mass and renal blood flow. However, clearance can also be affected by comorbid conditions associated with obesity like chronic kidney or liver disease. Variations in the clearance of obese patients may affect maintenance dosing requirements.

 species and exhibit free-drug 24-hour area under the curve relative to the organism mean inhibitory concentration (

AUC/MIC targets were originally established in murine models then subsequently validated in retrospective human studies. Species-specific targets for echinocandins are 

This review aims to provide echinocandin dosing considerations in obese patients from the available literature.

Anidulafungin demonstrates linear PK with typical doses and protein binding approximating 99%.

 Anidulafungin is generally given intravenously (IV) as a loading dose of 200 mg followed by a maintenance dose of 100 mg daily for most indications and 200 mg daily for endocarditis or cardiac device infections.

 Anidulafungin clearance is unique amongst the echinocandins in that it undergoes non-hepatic spontaneous biodegradation.

Liu et al studied pooled patients from phase 2 and 3 clinical trials to assess the impact of obesity on clinical outcomes and anidulafungin PK parameters. Included for analysis were 262 patients. Weight was found to be modestly negatively associated with decreased AUC but not to a clinically significant degree. When comparing patients at the extremes of weight (40 kg vs. 150 kg), similar clinical efficacy and safety outcomes were observed.

 Hutton et al, in a retrospective study of 173 critically ill patients with candidemia treated with anidulafungin, found no difference in mortality between obese and non-obese patients.

Other PK analyses have shown variable results. Wasmann et al, in a single-dose PK study of 20 healthy obese and non-obese volunteers found that obese patients had a lower AUC due to increased clearance and Vd, though these patients did not have clinical disease.

 Similarly, Luque et al in 23 critically ill patients with invasive fungal infections and Dowell et al in 225 patients with serious fungal infections found weight was positively associated with clearance.

 Conversely, Liu et al in a population PK study of 454 patients with invasive aspergillosis and Bruggemann et al in a PK study of 36 critically ill patients with invasive fungal infections found no effect between weight on anidulafungin PK.

In summary, multiple clinical studies have found no difference in clinical outcomes between obese and non-obese patients treated with anidulafungin. Additionally, PK studies have had mixed findings and even those with detectable signals have acknowledged unclear clinical significance. Thus, the data does not appear to support dose adjustments of anidulafungin for obese patients.

Caspofungin generally displays linear PK with conventional doses and protein binding is high, exceeding 90%.

 Caspofungin is traditionally given as a loading dose of 70 mg IV once followed by a 50 mg IV daily maintenance dose thereafter. A higher dosing regimen of 150 mg daily is used for endocarditis or cardiac device infections.

 Caspofungin, similar to other echinocandins, is generally well tolerated even at higher doses (ie, 150 mg daily).

Ryan et al performed a post hoc pooled analysis of patients from phase 3 and 3 clinical trials of caspofungin to assess comparative efficacy and safety between obese and non-obese patients. In total, 1,134 patients across nine trials were evaluated, 163 (14%) were obese and 312 (28%) were overweight. The authors found no difference in clinical success and adverse drug reactions between obese and non-obese patients. This effect held true for studies of esophageal candidiasis, invasive candidiasis, and empirical therapy. There was a signal towards poorer outcomes in studies of invasive aspergillosis, though this is not a condition for which echinocandins are generally used as monotherapy.

Findings from PK studies of caspofungin in obese patients have been inconsistent. Two dose ranging studies conducted by Wurthwein et al and Muilwjik et al demonstrated either no impact or a detectable but clinically insignificant impact of weight on caspofungin clearance for doses between 50 to 200 mg daily. Of note, Wurthwein et al did find a 20% lower caspofungin AUC in patients weighing 80 kg vs those weighing 60 kg but this was not assessed to be sufficiently clinically meaningful given pharmacodynamic targets were still met. Both studies concluded that standard caspofungin dosing may be adequate for obese patients.

However, 2 subsequently published PK studies had opposing findings. van der Elst et al in an analysis of 20 critically ill patients found a positive association between weight (defined overweight as ≥80 kg) and caspofungin clearance as well as Vd. Based on these findings, the authors recommended a weight-based dosing regimen of 1 mg/kg/day.

 Martson et al in a study of 15 critically ill patients found a similar association (defined overweight as ≥120 kg) and recommended a loading dose of 2 mg/kg followed by a maintenance dose of 1.25 mg/kg/day to optimize AUC.

Taken together, there does not appear to be strong clinical evidence to support universally increasing dosing of caspofungin in obese patients. Obesity does not appear to impact clinical outcomes for patients with invasive and non-invasive candidiasis treated with caspofungin. That said, findings from PK analyses suggest risk of inadequate exposure, particularly in critically ill obese patients. Given the reliable safety profile of caspofungin and lack of dose-dependent toxicity in doses up to 150 mg daily, clinicians may consider a modest dose increase (eg, 70 mg daily) on a case-by-case basis in critically ill patients with severe candida infections receiving 50 mg daily dosing. A referenceable weight cutoff is used by the European Medicines Agency, which recommends using a maintenance dose of 70 mg daily (instead of 50 mg daily) in patients weighing 80 kg or greater.

Obesity significantly impacts the pharmacokinetics (PK) of antifungal drugs like echinocandins, including volume of distribution (Vd) and clearance. However, despite these PK differences, current clinical evidence generally does not support the need for universal dose adjustments in obese patients. Clinicians should consider personalized dosing based on patient characteristics, infection severity, and specific drug properties due to echinocandins' favorable safety profiles.

Evan Loh, MD, Chief Executive Officer, Paratek Pharmaceuticals

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