News Scan for Jul 27, 2021

News brief

Republicans COVID vaccine acceptance up 7% after party endorsements

Republicans' intended COVID-19 vaccine uptake rose 7% after watching and reading endorsements from elite Republican leaders versus those from Democrat leaders, according to a study published yesterday in the Proceedings of the National Academy of Sciences.

The researchers surveyed 1,480 self-identified Republicans from Mar 17 to 24, splitting them into three groups. One group watched a 2-minute vaccine endorsement speech by former President Donald Trump and then read an essay on how Republicans contributed to vaccine development and distribution; another experienced a similar intervention, except with Democrats such as President Joe Biden. The control group received information on an unrelated topic (neck ties).

Unvaccinated Republicans exposed to the Republican endorsements reported a 7.0% higher vaccination intention versus those who saw the Democratic endorsements and a 5.7% higher intention than those in the control group. The surveys indicated this was largely because the respondents believed the politicians wanted them to get vaccinated (vs, for example, wanting the Republicans to get credit for their efforts in the COVID-19 vaccination program).

Some data indicated that there was backlash to the Democrat endorsements, especially among vaccinated Republicans. The researchers say this could be because the intent to vaccinate among unvaccinated Republicans was already low.

"These results demonstrate the relative advantage of cues from Republican elites—and the risks of messaging from Democrats currently in power—for promoting vaccination among the largest vaccine-hesitant subgroup in the United States," the authors write.
Jul 26 Proc Nat Acad Sci study

Early COVID-19 outcome prediction models may need recalibration

COVID-19 tools developed early in the pandemic to predict clinical outcomes may need some recalibration now, according to a research letter today in JAMA Network Open.

The researchers looked at the results of a predictive model originally validated in a study published Oct 30, 2020, and compared them with the model's ability to predict the outcomes of 2,892 COVID-19 patients at the same six healthcare facilities from Jun 7, 2020, to Jan 22, 2021. Of the patients, 4.4% needed intensive care unit admission, 2.4% needed mechanical ventilation, and 5.8% died.

The model's performance for predicting mortality had a 0.83 area under the receiver operating characteristic curve (AUC), which was slightly lower than the AUC from the original modeling period, which was 0.85. (AUC is a measurement of the test's usefulness, with 1 being a perfect test.) Positive predictive values (PPVs) and negative predictive values (NPVs) also changed, showing 0.22 and 0.98, respectively, when using a cutoff corresponding to the highest 20% of predicted risk derived in the training set; the previous results showed a PPV of 0.46 and an NPV of 0.97.

The researchers say the large drop in PPV for mortality may be due to the lesser association between mortality and mechanical ventilation over time.

Similar results were seen for the composite illness severity outcome, with a lower AUC (0.78 vs 0.81) and PPV (0.25 vs 0.55). NPV rose a bit, coming in at 0.95, compared with 0.91.

"Our results indicate that the population of individuals hospitalized for COVID-19 has shifted and the prevalence of the studied outcomes changed. However, they suggest that prediction models derived earlier in the pandemic may maintain discrimination after recalibration," the researchers conclude.
Jul 27 JAMA Netw Open study

BioNTech launches malaria vaccine development project

BioNTech, the German biotechnology company that teamed with Pfizer to produce one of the two mRNA COVID-19 vaccines, yesterday announced the launch of a project to develop a malaria vaccine using the same platform.

In a statement, it said its goal is to deliver a safe and highly effective mRNA vaccine with durable immunity to prevent malaria infections and deaths. It will assess multiple vaccine candidates that target known malaria targets, such as circumsporozoite protein and new antigens identified during preclinical studies. The first clinical trial is slated to start at the end of 2022.

The company said another goal is to ramp up sustainable vaccine production and supply solutions with African manufacturers with the capacity to make various mRNA vaccines, part of a broader effort to expand vaccine access to low- and middle-income countries.

BioNTech said it is developing vaccines against nine different infectious diseases, with clinical trials of a tuberculosis vaccine candidate expected to begin in 2022.
Jul 26 BioNTech press release

Stewardship / Resistance Scan for Jul 27, 2021

News brief

Study: Use of restricted antibiotics rose after hospital ASP discontinued

The discontinuation of an antimicrobial stewardship program (ASP) at a South Korean hospital led to a rapid return of antibiotic use patterns observed before the ASP was implemented, researchers reported yesterday in Clinical Microbiology and Infection.

The interrupted time-series analysis looked at antibiotic use at the 859-bed hospital from September 2015 through August 2019. The hospital ASP, which focused on restricting the use of certain antibiotics, was implemented in September 2016 and discontinued in March 2018 after an infectious disease (ID) specialist resigned. Infection control measures at the hospital remained largely the same throughout the study period.

Immediately after discontinuation, the use of restrictive antibiotics increased by 41.06 days of therapy (DOT) per 1,000 patient-days in the hospital's general ward and by 391.04 DOT/1,000 patient-days in the intensive care unit (ICU). Increases were driven by the use of carbapenems in the general ward and ICU and glycopeptides in the ICU. In addition, there were positive changes in the slope for the use of restrictive antibiotics in the general ward and the ICU.

While the use of broad-spectrum antibiotics declined after discontinuation of the ASP, the study authors suggest a large proportion of broad-spectrum antibiotic prescribing may have been shifted to restrictive antibiotics.

"Therefore, instead of a reduction in the use of broad-spectrum antibiotics, the use of restrictive antibiotics increased," the authors wrote. "We suggest that the restrictive intervention for antibiotics is probably not educative and is not sustained."

The study notes that the number of active ID specialists in South Korea is limited, and that despite an emphasis on the importance of antimicrobial stewardship, many ASPs have been discontinued because of a shortage of workers.
Jul 26 Clin Microbiol Infect study

FDA rejects new drug application for sulopenem

Pharmaceutical company Iterum Therapeutics said yesterday that the US Food and Drug Administration (FDA) has rejected the company's new drug application (NDA) for approval of its oral antibiotic sulopenem etzadroxil/probenecid.

Iterum is seeking approval of the antibiotic for treatment of uncomplicated urinary tract infections (UTIs) in patients who do not do not respond to treatment with fluoroquinolones. But in a Jul 23 Complete Response Letter (CRL) to the company, the FDA said it could not approve the NDA in its current form.

While the FDA acknowledged the results of a phase 3 clinical trial indicated that patients with ciprofloxacin-resistant UTIs had a better response to oral sulopenem compared with ciprofloxacin, the agency said additional data from another clinical trial are needed to support approval for treatment of women with uncomplicated UTIs caused by fluoroquinolone-resistant pathogens.

The FDA also recommended that Iterum conduct further nonclinical research to determine the optimal dosing regimen.

"We are disappointed in this outcome and believe that the data package submitted was adequate for the approval of oral sulopenem," Iterum Therapeutics Chief Executive Officer Corey Fishman said in a company press release. "Regardless, we will evaluate the points raised in the CRL for discussion with the FDA to determine an expeditious path forward. We remain confident in the value of, and unmet medical need for, oral sulopenem to treat multi-drug resistant infections, including fast-growing quinolone non-susceptible pathogens."

The company says sulopenem has received Qualified Infectious Disease Product and Fast-Track designations from the FDA for seven indications.
Jul 26 Iterum Therapeutics press release