Coverage From ID Week 2020

A new podcast episode featuring Mei Mei Hu of Covaxx, whose company has made great strides toward a preventive option in mere months.

What It's Like to Make a COVID-19 Vaccine

, the second most common cause of invasive candidiasis in the US, was found to be the most prevalent strain of 

 infection (CDI), and demonstrated a high rate of resistance to the antifungal, caspofungin.

Khursida Begum, PhD, University of Houston College of Pharmacy, Houston Texas reported in the virtual IDWeek 2020 Conference that her group had found 

 in 9.2% of stool specimens for patients with CDI, and that 70.2% of these proved resistant to caspofungin.

"The echinocandin class of antifungals, including caspofungin has become the preferred therapy for invasive candidiasis due to 

 and other species demonstrating decreased azole susceptibility," Begum explained."Caspofungin resistance has been uncommon, but reports suggest that the incidence is increasing, particularly among 

As antibiotic use and overuse can open environments for both 

 opportunistic infections, Begum suggests that the dysbiosis associated with 

 presents additional opportunity for overgrowth of 

Begum and colleagues found that the prevalence of 

 in stool of patients with CDI has not been well studied, however, and so sought to investigate the incidence of the potentially pathogenic 

 with CDI, and the susceptibility to antifungal treatment.

The investigators collected stool samples from1,241 patients with CDI, at 2 hospitals in Houston, Texas.The samples were cultured in brain heart infusion (BHI) broth, and then sub-cultured onto selective HardyChrom 

 agar.Isolates were identified with polymerase chain reaction (PCR) testing, and the 

 isolates were screened for caspofungin resistance on Muller-Hinton agar.

Begum reported that 14.8% (184/1,241) samples were culture positive for 

 was the most prevalent, in 9.2% of samples, followed by 

 isolates (70.2%, 80/114) were caspofungin resistant.

"The results of this study showed that colonization of 

is common in patients with CDI and could be a source of antifungal-resistant pathogens," Begum reported.

 of the emergence of resistant Candida species, Andrea Cortegiani, MD , Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy, and colleagues, note that resistance to azole remains uncommon in 

, estimating an occurrence in less that 5% of clinical infections, but is found in 4 to 16% of 

Cortegliani and colleagues note that echinocandin resistance is associated with cross-resistance to azoles.They cite one study in which echinocandin resistance increased from 4.9 to 12.3%, and resistance to fluconazole from 18 to 30% in a 10-year period.

"Acquired resistance following echinocandin exposure appears to be on the rise," Cortegliani and colleagues indicate, "and the emergence of multi-resistant species among 

 poses a serious threat to critically ill patients."

Cortegliani and colleagues are hopeful that development of new glucan-synthase inhibitors, which are structurally different from echinocandins, will prove to be an effective option for multidrug resistant 

Articles

Invasive C  glabrata found to be most prevalent strain of Candida in stool of patients with C difficile infection, and likely resistant to caspofungin. 

Invasive Candidiasis with C diff is Likely Resistant to Antifungal

 When will pediatric patients be assessed?


 The inflection point of vaccine development


What is the trial participation commitment?


Last Friday, the US Food and Drug Administration (FDA) hosted a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to discuss 

 research, development, and eventual licensing with the Center for Biologics Evaluation and Research (CBER).

Though the live-broadcast meeting did not weigh any regulation decision nor tailor its agenda to any single vaccine candidate or company, it provided the public a glimpse into the mindset of the FDA’s key experts weeks prior to anticipated Emergency Use Authorization (EUA) applications for COVID-19 vaccines.

The advisory committee meeting also allowed for community-based input—of which there was plenty, as advocacy and health organizations alike represented differing patient populations, issues in disparity, and calls for scrutinous, transparent regulation of any possible vaccines.

In this week’s episode of Vaccine Race, Donald Alcendor, PhD, rejoined the limited series to give real-time takeaways from the VRBPAC meeting and what discussion could implicate for COVID-19 vaccine regulation. Among topics, the expert from Maharry Medical College and Vanderbilt University School of Medicine provided perspective on secondary phase 3 assessment endpoints, mandated vaccination groups, pediatric treatment arms, and advocacy representation at the meeting.

for the treatment of adult and children hospitalized with COVID-19 breaking a day prior, Alcendor also discussed what the decision could mean for eventual vaccine authorization.

Podcasts

A glimpse into FDA advisor perspective just weeks before EUAs are anticipated to be sent.

COVID-19 Vaccine Race: FDA Advisory Committee Meeting with Donald Alcendor, PhD

Johnson & Johnson (J&J) announced it is preparing to resume their COVID-19 vaccine trial. While they did not set a timetable, this signals a return to their study after a pause to their trial back in mid-October.

They paused their trial a couple of weeks ago due to an unexplained illness in a vaccine participant. “We have temporarily paused further dosing in all our COVID-19 vaccine candidate clinical trials, including the phase 3 ENSEMBLE trial,” the company said in a statement at that time.

The company did not offer any more information about the illness when it happened. “We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information.”

And in the latest statement the company still did not disclose the illness. “After a thorough evaluation of a serious medical event experienced by one study participant, no clear cause has been identified,” the company said in a statement. “There are many possible factors that could have caused the event. Based on the information gathered to date and the input of independent experts, the Company has found no evidence that the vaccine candidate caused the event.”

The independent Data Safety and Monitoring Board (DSMB) overseeing J&J’s Trial has recommended resuming trial recruitment. Following consultation with the U.S. Food and Drug Administration, preparations to resume the trial in the United States, including submissions for approval by the Institutional Review Boards, are now underway. Discussions with other regulators around the world to resume the clinical trial program are progressing.

J &J’s ENSEMBLE trial is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single dose of a vaccine versus placebo in up to 60,000 adults 18 years old and older, including significant representation from those who are over age 60.

The company is planning to move forward after receiving a recommendation from the DSMB to start up the trial again.

J&J Prepares to Resume COVID-19 Vaccine Trial 

A patient in Vienna, Austria was admitted to a local hospital. The 45 year old woman had a 7 day history of cough, weakness, myalgia, fever, and dyspnoea. She also had a 4 day history of nausea and diarrhea.

The next day after admittance, her condition worsened, and the patient was put on a ventilator.

In discussing potential treatment options, the attending physicians, family, and infectious disease experts decided upon a course of treatment for compassionate use.

An investigational therapy, APN01, developed by Austria-based Apeiron was started with intravenous infusion for 5 min twice daily. The investigators reported the patient became afebrile within hours.

APN01 is a recombinant form of the human angiotensin-converting enzyme 2 (rhsACE2), and this compound is the crucial severe acute respiratory syndrome SARS-CoV-2 receptor and protects multiple tissues, including the lung from injury as a regulator of the renin—angiotensin system.

The next day the patient’s temperature rose suggesting bacterial pneumonia. She was treated with cefuroxime.

The patient also was diagnosed dealt with methicillin-sensitive 

The patient was released after 57 days in the hospital.

The study’s lead author Alexander Zoufaly, MD, Department of Infectious Diseases/Clinic Favoriten spoke with 

 about the specifics of the case and offered some insights into the investigational therapy.

Videos

A case study examines a treatment for a hospitalized case of the virus.

Investigational Therapy Treats Severe Case of COVID-19 

At least 10% of patients with life-threatening coronavirus diseases 2019 (COVID-19) pneumonia have antibodies that attack their own interferons, according to a new study by a team of international investigators.

, found that 101 out of 987 patients with severe COVID-19 pneumonia had IgG autoantibodies that neutralize the ability of type 1 interferons to block SARS-CoV-2 infection.

“This was a huge surprise, much unexpected,” corresponding author Paul Bastard, affiliated with Inserm, University of Paris Imagine Institute and St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University, told 

®. “Very surprising how it mimics genetic inborn errors of immunity. Extremely surprising too that individuals with complete genetic defects in key interferon genes (as described in Zhang Q and al., Science, 2020) were adult patients who had not suffered previously from severe viral infections.”

, the team detailed genetic variants contributing to life-threatening COVID-19 pneumonia. Loss-of-function variants at 13 human loci known to govern TLR3- and IRF7-dependent type 1 interferon immunity to influenza virus were examined. Genetic defects leading to impaired production or response to type 1 interferons were reported in 23 patients (3.5%).

The twin studies come from lab of Jean-Laurent Casanova, MD, PhD, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at the Rockefeller University, and the COVID Human Genetic Effort, a international collaboration aiming to determine how human genetics determine severe COVID-19.

The antibody study included 987 patients with critical COVID-19, 663 asymptomatic or pauci-symptomatic patients with COVID-19, and 1227 healthy controls. Autoantibodies were found in none of the patients with asymptomatic or mild COVID-19 and in only 4 of the healthy participants. Based on this, the estimated prevalence of these autoantibodies in the general population is 0.33%.

The study also could help explain why men have been more adversely affected by COVID-19 than women, finding that 95 of the 101 patients with the autoantibodies were men.

The neutralizing autoantibodies are believed to have been present before SARS-CoV-2 infection and caused the severity of the disease. They were identified in 2 patients before infection and 3 patients with APS-1, a serious but rare immune diseased marked by a high concentration of antibodies against interferons, had life-threatening COVID-19.

“It would be important to implement routine testing for auto-antibodies in all patients infected with COVID-19 to be able to implement adequate treatments and preventive measures. And perform genetic testing in the patients with unexplained severe COVID-19,” Bastard said.

Treatment could include early injected or nebulized IFN-β because autoantibodies that work against that type of interferon are rare among those affected, while treatment with IFN-α is unlikely to be affective, the study said.

Early intervention might be key. Once patients are hospitalized, it might be too late for treatment to show benefits. The World Health Organization 

 recently released results indicating that interferon-beta therapy didn’t lower mortality nor the need for ventilation among more than 2,000 people who received the drug.

Autoantibodies that attack type 1 interferons, neutralizing the immune system’s ability to block the SARS-CoV-2 virus, were present in 10% of patients with life-threatening coronavirus diseases 2019 (COVID-19) pneumonia, a new study found.

Autoantibodies Block Interferons in 10% of Severe COVID-19 Cases

The conclusion to the independent safety review punctuates a 50-day period of scrutiny and discussion around 2 non-fatal adverse events reported in patients.

FDA Clears AstraZeneca COVID-19 Vaccine to Resume US Trial

Here is a look at the patterns within the variety of symptoms and presentations during physician exams.

Delving Deeper into Post Ebola Syndrome

A presenting author offers greater study insights into this novel therapy for the treatment of serious infections. 

Understanding Cefiderocol and the Results of the CREDIBLE-CR Study

The study population comprised 224 patients admitted to the ICU with influenza, and the overall rate of IPA was 3.1% (7/224). 

Rates of Invasive Pulmonary Aspergillosis in ICU Patients With Influenza Far Lower Than Previously Thought

Its phase 3 COVE trial enrollment is complete and  the company is working towards its goal of FDA approval. 

Moderna Reaches Full Enrollment for its COVID-19 Vaccine 

Reports of hospitalized older adults with COVID-19 who do not experience the classic symptoms are on the rise. 

Long-Term Care Facility Residence Associated With Atypical Presentation of COVID-19

“The compound appears to be safe and well-tolerated, [and we observed] excellent efficacy based on a very small sample size,” Peter G. Pappas, MD, said.

Fosmanogepix Shows Promise as an Effective Novel Antifungal in POC Trial

The urgent care setting is a prime target for antimicrobial stewardship efforts as it becomes an increasingly prevalent form of healthcare delivery. 

Antibiotic Stewardship in the Urgent Care Setting Cuts Antibiotic Prescribing for Respiratory Encounters

A firsthand look into a Kentucky program that's initiated opioid use disorder care in recurring HIV, hepatitis C patients.

Starting Addiction Care with Injection Drug-Infected Patients

A prospective study looked at the association of contract nursing and SARS-CoV-2 outbreaks. 

Top Medical News

Invasive Candidiasis with C diff is Likely Resistant to Antifungal

COVID-19 Vaccine Race: FDA Advisory Committee Meeting with Donald Alcendor, PhD

J&J Prepares to Resume COVID-19 Vaccine Trial

Investigational Therapy Treats Severe Case of COVID-19

Autoantibodies Block Interferons in 10% of Severe COVID-19 Cases

Most Recent