Phase 3 trial provides more positive data for recurrent C diff microbiome drug

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A phase 3 clinical trial found that SER-109, an investigational microbiome therapeutic for the treatment of recurrent Clostridioides difficile infection (CDI), was well tolerated and showed clinical benefit in a population with prevalent comorbidities, researchers reported today in JAMA Network Open.

The single-arm ECOSPOR IV trial was conducted among two cohorts of adults who had a history of recurrent CDI: rollover patients from the ECOSPOR III trial who had a CDI recurrence within 8 weeks of receiving either SER-09—a therapeutic composed of Firmicutes bacterial spores—or placebo, and patients with at least one CDI recurrence.

Patients in both cohorts received four SER-109 capsules daily for 3 days following symptom resolution after initial antibiotic treatment. The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs), and cumulative rates of recurrent CDI through week 24. A total of 263 patients were enrolled from October 2017 to April 2022, with 29 in cohort 1 and 234 in cohort 2. Comorbidities were prevalent in the overall population.

Overall, 141 patients (53.6%) had TEAEs, which were mostly mild and gastrointestinal; none of the 8 deaths or 33 serious TEAEs were considered treatment-related. Just 23 patients (8.7%) had recurrent CDI at week 8 and 36 (13.7%) at week 24. Analysis by select baseline characteristics showed consistent low rates of recurrent CDI up to week 8 in all subgroups, but rates were lower in patients younger than 65 years compared with those 65 and older (4.0% vs 13.1%) and in patients enrolled based on positive polymerase chain reaction results versus those with positive toxin enzyme immunoassay results (4.3% vs 10.4%).

These data support an important role for SER-109 as part of a paradigm shift.

The investigators say the combined safety data from this trial and efficacy data from the ECOSPOR III trial, which demonstrated the superiority of SER-109 compared with placebo in reducing CDI recurrence, suggest that the use of purified Firmicutes spores benefits patients with recurrent CDI.

"These data support an important role for SER-109 as part of a paradigm shift in the clinical management of recurrent CDI," they wrote.

Increased antibiotic prescribing for respiratory infections seen in England during COVID-19

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An analysis of patient-level primary care data shows that antibiotic prescribing for upper respiratory tract infections (URTIs) increased in England in the 2 years after COVID-19 lockdown measures were implemented, researchers reported late last week in JAC-Antimicrobial Resistance.

Using IQVIA data on patients who were diagnosed as having a URTI at general practices in England from April 2014 through May 2022, researchers with the UK Health Security Agency, IQVIA, and the London School of Hygiene and Tropical Medicine conducted an interrupted time series analysis to compare antibiotic prescribing for URTI consultations before and during the pandemic. They identified 518,859 patients with at least one URTI consultation during the study period, 50.7% of whom received an antibiotic.

Results revealed that antibiotic prescribing rates for URTI consultations were decreasing before the pandemic. But there was an immediate, significant increase of 105.7 antibiotic items per 1,000 URTI consultations at the beginning of the pandemic, which corresponded to a 27% increase compared with the predicted value for April 2020 had pre-pandemic trends continued. A significant increase in prescribing during the pandemic was seen across all subgroups, with the greatest increase observed in patients aged 12 to 17 years. The increases were mostly sustained to May 2022.

We recommend that other countries consider conducting similar analyses.

Although overall consultation rates for URTI declined substantially in England following the introduction of measures to reduce the spread of COVID-19, the authors note that telephone consultations rose by 270%, and they suggest that the diagnostic uncertainties arising as a consequence of conducting remote clinical assessments may have resulted in more clinicians being likely to prescribe antibiotics for URTIs. But they say the persistent increase in prescribing seen through May 2022 is concerning.

"We recommend that other countries consider conducting similar analyses to assess the impact of the pandemic on antibiotic prescribing," they wrote. "Future studies should consider investigating consultation setting on prescribing rates, and patient and prescriber attitudes."

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