Ridinilazole Triggers Sustained Clinical Response in CDI and Inhibits Recurrence of Infection | Latest news for doctors, nurses and pharmacists

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In patients with Clostridioides difficile infections (CDI), treatment with ridinilazole (RDZ) leads to high and sustained rates of clinical response, according to a study presented at the recent Virtual ID Week 2022. Compared to vancomycin (VAN), RDZ also prevents more strongly recurrent CDIs (rCDIs).

Researchers conducted a global, phase III, double-blind, randomized trial recruiting 759 patients, 745 of whom were included in the modified intention-to-treat analysis. RDZ was given at 200 mg twice daily, while VAN was given at 125 g every 6 hours.

The primary endpoint was sustained clinical response (SCR), defined as CR and the absence of rCDI for 30 days after the end of treatment.

Seventy-three percent of patients treated with RDZ achieved the primary outcome, while 70.7% did so in the VAN group. The difference was not statistically significant (p=0.4672). [IDWeek 2022, abstract 730]

However, when examining the individual components of the SCR, the researchers found that the RDZ significantly protected against recurrence, producing a rate less than half that of the VAN comparators (8.1% vs. 17.3%; p= 0.0002). This effect was more pronounced in the subgroup of patients not taking other antibiotics (6.7% in the RDZ versus 16.5% in the VAN; p=0.0005).

Gentle on the gut microbiome

According to the researchers, VAN has been shown to be an effective treatment for CDI, typically achieving >80% clinical response. However, the recurrence rate of infection remains high after NPV at around 20% to 30%. One potential reason for this is that VAN is a nonselective antibiotic, which also affects other microbiome organisms, resulting in gut dysbiosis.

Several species of gut microbes convert primary bile acids to secondary bile acids, which in turn exert inhibitory effects against
It’s hard germination. RDZ is being developed as a highly selective, DNA-binding antibiotic. To assess these properties, the researchers defined key microbiome parameters, such as diversity, composition and levels of secondary bile acids, as secondary endpoints.

Their analysis showed that immediately at the end of treatment, RDZ-treated patients had significantly higher alpha diversity than VAN comparators (p

The relative abundances of major microbial phyla were also significantly better in the RDZ arm. At the end of the treatment, VAN contributed to a strong disruption of the microbial profile, leading to a greater relative abundance of Proteobacteria and Firmicutes, while eliminating almost all species of Bacteroidetes.

In the RDZ group, the Bacteroidetes phylum retained a relative abundance of 31% at the end-of-treatment evaluation.

Relative abundance rebounded in both groups 40 days after the end of treatment but remained numerically better in the RDZ arm. Secondary bile acid levels were also significantly higher in the RDZ arm at the end of treatment (p

The researchers also found that greater microbiome diversity was significantly correlated with higher SCR and lower rCDI. The same was true for higher concentrations of secondary bile acids.

In terms of safety, treatment-related adverse events occurred in 36.4% of RDZ patients and 35.5% of VAN patients. Only 0.8% of the RDZ arm was discontinued due to toxicities, compared to 2.9% in the VAN comparators.

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