Contagion Editorial Team

The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) announced today it had added 3 new evidence-based guidelines for the treatment of 

The guidelines, developed by a multidisciplinary panel with representatives from IDSA and SHEA, include 3 recommendations on suggested treatments for patients with initial and recurring CDI episodes, based on new data for fidaxomicin and for bezlotoxumab, a monoclonal antibody targeting toxin B produced by 

According to the panel, the recommendations are the result of systematic review of available evidence and an assessment of the benefits and harms of alternative care options. The panel adhered to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and strength of recommendations. The guidelines are intended to aid clinicians in determining which treatments are best for individual patient scenarios.

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The organizations set out 3 recommendations for initial and recurrent C diff treatment.

IDSA, SHEA Announce New Clostridioides Difficile Clinical Guidelines

Gilead announced today positive data from 3 retrospective studies, which observed that hospitalized patients who received remdesivir had significantly lower risk for mortality compared with matched controls.

This news was presented as posters at the World Microbe Forum (WMF) this week.

Two of the analyses came from retrospective studies, which also observed that patients who received the therapy had a significantly increased likelihood of discharge from the hospital by Day 28. These retrospective studies observed treatment trends and outcomes in the United States from the HealthVerity and Premier Healthcare databases.

The third analysis compared clinical outcomes in patients receiving a 10-day treatment course of remdesivir in the extension phase of the global, open-label SIMPLE-Severe study with patients receiving standard of care in a real-world retrospective longitudinal cohort study.

This reduction in mortality was shown across a spectrum of baseline oxygen requirements. The results were also consistently observed at different timeframes over the course of the pandemic and across geographies, according to Gilead.

“Clinical trials help us understand the efficacy and safety profile of a treatment, but their size can limit our ability to assess all potential aspects of a treatment’s effect due to low event rates in the trials. Large real-world datasets with greater sample sizes and robust methodologies can be helpful to assess treatment effects in both the overall patient population and in clinically relevant subsets of patients,” Robert L. Gottlieb, MD, PhD, cardiologist at Baylor University Medical Center and Baylor Scott & White Research Institute, said. “These real-world analyses provide clinicians with additional data on the efficacy of remdesivir (Veklury) in patients hospitalized with COVID-19, including its effect on mortality and likelihood of discharge from the hospital.”

he HealthVerity Analysis they looked at assessed mortality and the likelihood of discharge in hospitalized COVID-19 patients who were treated with Veklury (n=24,856) versus matched controls (n=24,856) between May 1, 2020 and May 3, 2021. Controls were matched 1:1 to patients treated with Veklury using risk set sampling on date of admission, number of days from admission to start of Veklury, age, gender, baseline oxygen support requirement and corticosteroid use. A 1:1 propensity score matching was applied to establish comparable groups based on baseline clinical and demographic characteristics, comorbidities and concomitant medications. The primary endpoint was time to death.

This analysis found that in the overall population, patients receiving remdesivir had a statistically significant 23% lower mortality risk compared with controls (HR:0.77, 95% CI:0.73 to 0.81), regardless of baseline oxygen requirement. Overall, a significantly greater likelihood of discharge by Day 28 was observed in patients completing a full five-day course of remdesivir compared with controls (HR:1.19, 95% CI:1.14 to 1.25); this result was most pronounced in patients with lower oxygen requirements at baseline.

In the Premier analysis, they assessed mortality in hospitalized patients who were treated with remdesivir (n=28,855) versus matched patients who were not treated with remdesivir (n=16,687) between August and November 2020. The analysis included adult hospitalized patients who were treated with remdesivir within the first two days of hospitalization with those not treated with remdesivir during their hospitalization. Patients were matched on baseline level of oxygenation, hospital, within a 2-month hospital admission period, and all stayed in the hospital for a minimum of 3 days after initiating treatment. The primary endpoint was time to death.

In this analysis, patients overall who were treated with remdesivir had a significantly lower risk of mortality both at Day 14 (HR:0.76, 95% CI:0.70 to 0.83, p<0.0001) and at Day 28 (HR:0.89, 95% CI:0.82 to 0.96, p=0.003) compared with patients who did not receive Veklury. Patients who were treated with remdesivir and received either no oxygen (HR:0.69, 95%, CI:0.57 to 0.83, p<0.001), low-flow oxygen (HR:0.68, 95% CI:0.60 to 0.77, p<0.0001) or invasive mechanical ventilation/ECMO (HR:0.70, 95% CI:0.58 to 0.84, p=0.0001) at baseline had a significantly lower risk of 14-day mortality. 

A significant reduction in mortality was also noted at 28 days for these same groups of patients, no oxygen (HR:0.80, 95%, CI:0.68 to 0.94, p=0.007), low-flow oxygen (HR:0.77, 95% CI:0.68 to 0.86, p<0.0001) or invasive mechanical ventilation/ECMO (HR:0.81, 95% CI:0.69 to 0.94, p=0.007). Patients on high-flow oxygen at baseline who received remdesivir also had significantly lower 14-day mortality (HR:0.81, 95% CI:0.70 to 0.93, p=0.0043); at 28 days, the difference in mortality in patients receiving high-flow oxygen at baseline was not statistically significant (HR:0.97, 95% CI:0.84 to 1.11, p=0.646)

The SIMPLE-Severe study was a randomized, open-label, multicenter, Phase 3 study in hospitalized adult patients with severe COVID-19 (oxygen saturation of ≤94% on room air, or receiving supplemental oxygen and radiological evidence of pneumonia); these results have been previously presented. As the primary objective of the study was to evaluate five-day and 10-day dosing durations of remdesivir, the initial phase of the study did not include a standard of care comparator arm. The retrospective real-world analysis presented at WMF compared mortality outcomes of hospitalized patients with COVID-19 who received remdesivir in the open-label extension phase of the SIMPLE-Severe study (n=1,974) versus propensity-score weighted patients from a real-world retrospective longitudinal cohort study of hospitalized patients with COVID-19 who were not treated with remdesivir (n=1,426). Propensity score weighting was used to ensure consistent baseline demographics, region, clinical characteristics, concomitant medications and comorbidities. The primary endpoint was time to all-cause death.

This analysis found that in the overall population, treatment with remdesivir was associated with a statistically significant 54% lower mortality risk at 28 days versus those not treated with remdesivir regardless of a patient’s baseline oxygen requirements (HR:0.46, 95% CI:0.39 to 0.54, p<0.001). Patients who completed a full 10-day course of remdesivirhad a significantly shorter time to discharge within 28 days compared with those who did not receive remdesivir(HR:1.64, 95% CI:1.43 to 1.87, p<0.001); the result for time to discharge was not significant for patients receiving invasive mechanical ventilation or ECMO at baseline (HR:0.92, 95% CI:0.62 to 1.36, p=0.68).

Investigators looked at data from 3 analyses showed a reduction in mortality was observed across a spectrum of baseline oxygen requirements, at different timeframes, over the course of the pandemic, and in various geographies.

Remdesivir Demonstrates Reduced Mortality in Hospitalized Patients With COVID-19 

The Food and Drug Administration (FDA) approved an expansion for the therapy, Nuzyra, to include an oral-only dosing regimen for the treatment of Community-Acquired Bacterial Pneumonia (CABP) in adults.

Manufactured by biopharmaceutical company, Paratek, Nuzyra is a novel antibiotic with both once-daily oral and intravenous (IV) formulations. The oral-only dose for CABP has an initial dose of 300 mg twice on day 1 and 300 mg once daily thereafter for a total of 7 to 14 days. A modernized tetracycline, NUZYRA is specifically designed to overcome tetracycline resistance and exhibits activity across a spectrum of bacteria, including Gram-positive, Gram-negative, atypicals, and other drug-resistant strains.

“The approval of an oral-only dose regimen for Nuzyra in pneumonia represents a significant opportunity to offer clinicians the ability to treat patients in either the outpatient or primary care setting,” Adam Woodrow, president and chief commercial officer of Paratek, said. “Treating in this way potentially reduces or eliminates hospitalizations and the associated risk and costs from a hospital stay.”

Nuzyra had initially been approved by the FDA in October of 2018, and was indicated for the treatment of CABP and acute bacterial skin and skin structure infections (ABSSSI).

Paratek’s omadacycline (Nuzyra) is granted approval for an oral-only dosing regimen in adults.

FDA Approves Expansion of Community-Acquired Bacterial Pneumonia Therapy

The European Council met today and decided to update its travel restrictions from countries outside the EU based on people’s vaccine status.

“Today E.U. ambassadors agreed to update the approach to travel from outside the European Union,” Wigand told reporters. The European Council “now recommends that member states ease some restrictions, in particular for those vaccinated with an EU-authorized vaccine.”

This means certain vaccines available in certain countries would grant acceptance to travel in the EU. For example, people who had vaccines available in the US would be allowed entry into Europe; however, vaccines being created and administered in China and Russia would not.

The EU has been working towards vaccinating its own population. Inside the EU member states, 237.5 million vaccines have been delivered, 173.3 million administered, and 31.8 million people have received at least 1 dose.

The EU member states consists of Austria, Belgium, Bulgaria, Croatia, Republic of Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain and Sweden.

It is important to note, the United Kingdom is not included in the EU as it chose to withdrawal in 2020, and these travel guidelines would not reflect traveling to those countries including England, Wales, Scotland, and Northern Ireland.

The EU is also creating a list of countries they regard as having their COVID-19 incidence rates under control, which would mean all travelers from these countries could travel to the EU no matter their individual vaccination status.

While this new travel guidance has not been formally adopted there does not appear to be any roadblocks ahead for it.

The European Union (EU) agrees to look at easing restrictions for travelers from outside the continent, depending on vaccine or country status.