Kevin Kunzmann

 who underwent a hematopoietic stem cell transplant (HSCT) also benefitted from frontline medications fidaxomicin or oral vancomycin, according to a recent study.

However, the new research—presented at the Making A Difference in Infectious Disease (MAD-ID) 2021 Annual Meeting—would infer one provides significantly lower risk of treatment failure over the other in such adult patients, according to the researchers.

Investigators from Atrium Health’s Carolinas Medical Center, led by Bliss Green, PharmD, sought to retrospectively evaluate clinical outcomes among patients with initial 

infection within 100 days after their stem cell transplant, treated with either fidaxomicin or oral vancomycin.

, the 2 agents provided similar outcomes in initial short and short-term mortality among adults with 

, but fidaxomicin provided a lower risk of infection recurrences at 1 month following treatment.

As Green and colleagues noted, hematopoietic stem cell transplant is generally associated with increased 

infection risk, without any specific treatment recommendations existing for the patient population.

“Fidaxomicin has been shown to have potential benefits over oral vancomycin, including decreased recurrence rates and the preservation of the intestinal microbiota,” they wrote, “however, there are limited data comparing therapies in HSCT recipients.”

Their single-center, retrospective cohort study of all adult transplant recipients diagnosed with initial 

infection episodes within 100 days of their procedure ran from March 11, 2014 to October 1, 2020. All observed patients had been treated with either agent.

infection diagnosis was based on the presence of at least 3 unformed stools within 24 hours, and/or physician-expressed concern for diarrhea, plus a positive test for infection on institutional protocol.

infection, a prior infection within 90 days of HSCT, fulminant 

infection, or mortality prior to completion of initial treatment were excluded from the cohort.

Investigators sought a primary outcome of recurrence at 30 days from therapy completion, and secondary outcomes including 

infection recurrence at 60 and 90 days, as well as clinical cure of infection, sustained clinical response, treatment failure, acute graft versus host disease (aGVHD) occurrence, and vancomycin-resistant enterococci (VRE) infection occurrence within 90 days after completing therapy.

Their assessment included 61 patients from 159 screening; of them, 22 received fidaxomicin and 39 received vancomycin.

Green and colleagues observed no differences in 30-day infection recurrence among patients receiving fidaxomicin (0%) versus those receiving vancomycin (10.3%; 

 = .287). They similarly observed similarity in clinical cure (100% vs 92.3%, respectively; 

 = .547), as well as sustained clinical response at 30 days (100% vs 84.6%, respectively; 

GVHD occurrence (50% vs 45.5%, respectively; 

 >.99) and VRE infection (0% vs 2.6%, respectively; 

 >.99) were similar in the fidaxomicin and vancomycin treatment arms.

However, treatment failure incidence was more frequent in the oral vancomycin group (38.5%) than the fidaxomicin group (4.6%; 

 = .005), in which patient diarrhea persisted enough to require a change in therapy regimen. Median therapy duration was 14 days with oral vancomycin, versus 10 days with fidaxomicin (

In their conclusion, investigators stressed the primary outcome similarities among the front-line agents in treating HSCT patients with 

“The rates of recurrence, clinical cure, and sustained clinical response in adult HSCT recipients with initial CDI treated with fidaxomicin or oral vancomycin were similar,” they wrote. “Fidaxomicin was associated with significantly lower rates of treatment failure compared to oral vancomycin.”

This article was originally published in ContagionLive.

Articles

Adult patients with Clostrioides difficile infection who received hematopoietic stem cell transplant also benefitted from frontline medications fidaxomicin or oral vancomycin.

Frontline Drugs Vancomycin, Fidaxomicin Found to Benefit Transplant Patients With C Difficile

New data from an unreviewed, preprint research article indicates first-dose immunization efficacy from Pfizer-BioNTech coronavirus 2019 (COVID-19) vaccine BNT162b2 is improved 51% after 13-24 days among Israel residents given the vaccine. The retrospective cohort assessment, pending review and publication, is among the first real-world indications of first-dose efficacy of the currently authorized mRNA vaccines for the pandemic.

Israel is currently the most vaccinated country against COVID-19, per capita, worldwide. According to Our World in Data, more than one-third of the total population has received at least 1 COVID-19 vaccine dose as of Thursday—or, nearly 3 million people. Off the strength of phase 3 results for BNT162b2&mdash;which was used to support its approved Emergency Use Authorization (EUA) under the FDA last month, and showed COVID-19 prevention efficacy of greater than 90% among adults after their second dose&mdash;the current understanding is that the Pfizer-BioNTech product is among the most promising prophylaxes for the pandemic virus.

That said, investigators wrote, real-life vaccine effectiveness evaluation during the rollout phase is “urgently needed, especially given the global disease surge.”

New data from an unreviewed, preprint research article indicate first-dose immunization efficacy of the Pfizer-BioNTech coronavirus 2019 vaccine improves by 51% 13-24 days post administration. 

Preprint Research on Pfizer COVID-19 Vaccine Shows Greater Efficacy Two Weeks Post Administration

Sanofi, one of the largest drug and vaccine producers in the world, has agreed to bottle and package at least 125 million doses of 

 BNT162b2 from Pfizer and BioNTech. The France-based company will use its Frankfurt facilities to aide in late-stage production for the vaccines from their pharmaceutical rivals, for distribution in the European Union, beginning this summer, according to an announcement made Wednesday.

In the meantime, Sanofi remains engaged in the development of its own COVID-19 vaccine, in collaboration with partner GlaxoSmithKline (GSK). The group most recently delayed its vaccine production and real-world assessment after observed failure to produce a strong immune response in older participants of a phase 1/2 trial.

The UK had originally ordered 60 million doses of the Sanofi and GSK vaccine, which investigators reported last month as having a low immune response in participants aged ≥50 years old, likely due to “insufficient concentration of the antigen.” This setback, combined with shortcomings in Pfizer-BioNTech production and delays from the AstraZeneca-University of Oxford vaccine—as well as a highly transmissible SARS-CoV-2 variant first observed in southeast England&mdash;has put significant strain on the region’s immunity-building efforts.

Sanofi has agreed to bottle and package at least 125 million doses of the COVID-19 vaccine BNT162b2 from Pfizer and BioNTech.

Sanofi to Aid in Production of Pfizer-BioNTech Vaccine

The FDA has approved atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb) for the treatment of adult and pediatric patients with Zaire ebolavirus​ (Ebola virus) infection. With the indication, the monoclonal antibody cocktail from Regeneron Pharmaceuticals becomes the first drug approved to treat Ebola virus. The 3-drug combination therapy is designed to target the glycoprotein located on the virus' surface, and inhibit its attachment to the cell receptor, stopping the virus from entering cells.

Its efficacy and safety was observed the PALM trial, a 382-adult and -pediatric patient assessment led by the US National Institutes of Health (NIH) and DRC's Institut National de Recherche Biomédicale as part of the expanded access program conducted in the Democratic Republic of the Congo (DRC) during an outbreak in 2018-2019. The multi-center, open-label, randomized controlled study compared 154 patients administered 50 mg of each monoclonal antibody in Inmazeb intravenously in a single infusion, versus 168 patients on investigational control therapy. Primary efficacy endpoint was 28-day mortality.

One-third (33.8%) of patients treated with Inmazeb died after 28 days, versus 51% of control patients. Investigators provided the therapy to another 228 patients in the expanded access program. The most common symptoms reported among treated patients included fever, chills, tachycardia, tachypnea, and vomiting—symptoms also closely associated with Ebola virus infection.

Atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb), a monoclonal antibody cocktail ffor the treatment of adult and pediatric patients with Ebola virus infection, becomes the first drug approved to treat Ebola virus.

Inmazeb Gets First FDA Approval for Ebola Treatment

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There is no perfect moment to timestamp the accelerated, massive movement toward finding and distributing the first vaccine candidates for the coronavirus 2019 (COVID-19) pandemic.

There are dozens of legitimate agents making earnest progress toward clinical consideration at an unprecedented pace—in this month alone, a pair of vaccine candidates of entirely different makeup and effect reached phase 3 assessment, while another couple of candidates were agreed upon for mass distribution with countries in billion-dollar deals.

These latter vaccines have yet to even compile a full body of efficacy, safety, and tolerability data—and yet, they are the hope of national leaders.

No, this unforeseen and nonlinear process of research, application, reporting, manufacturing, and distributing of vaccines has no point on its timeline reserved for reflection and forecasting. Rather, ‘sooner than later’ would be the most ideal time to discuss the COVID-19 vaccine race.

Last night, MJH Life Sciences hosted the COVID-19: Race for a Vaccine live webinar, featuring a distinguished trio of presenters:

Professor and Associate Director, Emory Vaccine Center

Professor, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine

Director, Emory-UGA Center of Excellence for Influenza Research and Surveillance (CEIRS)

Associate Research Scientist, Center for Infection and Immunity, Mailman School of Public Health, Columbia University

Mary Lowell Leary Emeritus Professor of Medicine, Infectious Diseases, Molecular Pharmacology, and Experimental Therapeutics

The virtual panel held lecture on the brief history, the current understanding, and the future practice of the COVID-19 vaccine process. As they did for their audience, here is a chronological breakdown of the discussion.

Rasmussen began the webinar with a quick update on the current tally of COVID-19 vaccine candidates: as per The New York Times this week, there are more than 140 preclinical vaccines, 18 in phase 1; 12 in phase 2; 6 in phase 3; and just 1 approved for limited use—a vaccine developed for use in the Chinese military.

Among the most basic principles of vaccine development, Rasmussen said, are the exposure to antigen (weakened virus being injected into the patient), an immune response to the antigen, and immunological memory.

Historically, vaccine platforms largely came in cross-protection, toxoid, inactivated, or live attenuated forms. All 4 of these platforms and their introduction to a greater array of vaccine indications have made for “game changers in public health,” Rasmussen said.

Despite traditional vaccines being most famous for their massive reduction of smallpox and polio deaths in the few years following vaccination, they do bear shortcomings: they are difficult to mass-manufacture, slow to develop, and can result in adverse effects.

Eventually, scientists developed improved vaccine platforms:

Subunit vaccines, which uses recombinant viral proteins as antigens

Nanoparticle vaccines, which uses a synthetic viruslike particles as recombinant antigens

Viral vector vaccines, which uses recombinant pseudotyped viruses as expressed antigen

Nucleic acid vaccines, which uses directly delivered nucleic acid (DNA or mRNA) encoding the antigen

Currently, investigators are assessing a half-dozen different vaccine platforms for the unique demands of SARS-CoV-2 prophylaxis: RNA/DNA vaccines, recombinant protein vaccines, vectored vaccines, inactivated vaccines, and live attenuated vaccines.

Among those to have reached phase 3 thus far have been an mRNA candidates from Moderna and the National Institutes of Health, plus a candidate from BioNTech/Pfizer and another from CureVac. The viral-vectored candidate from Oxford University/AstraZeneca is also at phase 3, as well as another candidate from Pfizer/BioNTech.

From their progression in good manufacturing practice (GMP) development, through all clinical phases of assessment, to regulatory approval and eventual distribution, administration, and developed immunity, Rasmussen anticipates the timeline may take anywhere from 6-18 months.

Poland began his session with a planted stance on the current state of debate on vaccines.

“You can have your own opinions, but not your own facts,” he said. “Science is not a democracy.”

Poland stressed the scientific process—which is intentional and explicit, emphasizing repeatability, generalizability and peer review while remaining agnostic to results, and at its best when open to inquiry and willing to question dogma.

Among the highlighted hurdles of vaccine development—or, “porcupines,” he so quipped&mdash;include public concern over “cutting corners,” the allocation of vaccine and whether it is done in utilitarian or egalitarian fashion, the national levels of distribution and supply, the costs and profiteering behind it, and the overlapping “negatively synergistic threats” including COVID-19, the flu, politics, the economy, and more.

The truth, Poland said, is that despite there being 3 novel coronaviruses cross species barrier to infect humans in the last 16 years, an influenza pandemic just a decade ago, and multiple national and global tabletop exercises in place to assure preparedness, the US is continually overwhelmed by COVID-19.

“While this may have been a shock, it should not have been a surprise,” Poland said, quoting an unfortunately similar summarization of national tragedy: The 9/11 Commission Report.

Ideally, a COVID-19 vaccine would have an excellent safety profile and capable of quick mass production, room temperature stability to avoid cold chain and transportation concerns, indefinite storage, and administration that does not require highly trained providers.

Maybe, Poland said, a few of these capabilities will be met.

“We have also not well defined vaccine efficacy targets,” Poland said. “Will it be prevention of infection? Prevention of disease? Reduction of transmission of disease?”

Based on the current standing of vaccine candidates in the development pipeline, Poland projected 4 likely scenarios:

A two-dose vaccine released in January 2021 by emergency use authorization (EUA) with a moderately high reactogenicity rate, 5% to 10% of individuals experiencing grade ≥3 serious adverse events, and an efficacy up to 60%.

A two-dose vaccine released in March 2021 by EUA, with a lower reactogenicity rate and a 70% efficacy rate.

A two-dose vaccine released in April 2021 under full licensure, with acceptable reactogenicity rate and estimated efficacy at 60% to 70%.

A one-dose vaccine released some time afterward, with a very low reactogenicity rate and efficacy up to 90%.

In all these scenarios, investigators would not be certain of long-term durability.

“My point is these are going to roll out, possibly through different mechanisms, over several months,” Poland said. “So now what? Neither the public nor providers are prepared for that. The distributor chain is not prepared for that.”

Poland also highlighted that the largest currently planned trials will have just 20,000 immunized persons. The adverse event rate for the most-assessed candidates will be just 1 per 5000.

“The fact is that part of vaccine development involves human behavior, which we are seeing play out worldwide,” Poland said.

Orenstein posted a series of questions which will likely still be unanswered at the time of a COVID-19 vaccine licensure. Among them are the duration of vaccine immunity, risk factors, the impact of the vaccine on reducing transmission, and the risk factors for if a vaccine fails or wanes in immunity.

“The key is we’re going to have to set up a monitoring system for safety and effectiveness in the long term,” he said. Such a program could borrow structure from similar systems like the FDA’s Vaccine Adverse Event Reporting System (VAERS), which operates more so as a hypothesis-generating feedback system for new vaccines.

Additionally, Orenstein suggested the idea of establishing vaccine priority—a guidance for which groups who should receive earliest consideration for available candidates.

In establishing vaccine priority groups, Orenstein stressed agencies must consider hurdles including an evolving understanding of COVID-19 epidemiology and immunology, a current absence of safety and efficacy data of COVID-19 vaccines, and the unknowns in vaccine dose timing and rate of supply.

The highest priority, Orenstein suggested, could be the healthcare and essential worker population (in order to maintain societal and treatment infrastructures), followed by the general population. These groups are comprised of approximately 122 million and 206 million Americans, respectively.

From there, both groups can be tiered by currently available vaccine supply and program planning—introducing potential SARS-CoV-2 immunity group-by-group in the US, as doses become available.

There is no perfect moment to timestamp the accelerated, massive movement toward finding and distributing the first vaccine candidates for the coronavirus 2019 pandemic.

Expert Panel Updates the Race for a COVID-19 Vaccine

Pre-exposure prophylaxis (PrEP) has become a fixture in HIV preventive strategy for the better part of a decade now. 

What may drive its increased use and adherence among at-risk patients is a multitude of factors just now coming into play: regional and state access assistance, improved research and collaboration, and individualized options for patients. In an interview with 

 during the International AIDS Society (IAS) AIDS 2020 Virtual Sessions last week, Philip Peters, MD, medical officer of the California Department of Public Health, discussed how the California PrEP Assistance Program (PrEP-AP) benefitted from a previous burden: an abundance of HIV cases in regions of the west coast.

As much as he and his colleagues have created a program foundation for other public health agencies, they’ve also benefitted from the work of others.

“It could be easier trying to figure out what’s working in another scenario then figure out if it works with what we’re doing, rather than figuring it out ourselves,” he explained.

Regional and state access assistance, improved research and collaboration, and individualized options for patients are key factors in adherence to PrEP.