Colon-targeted adsorbent may SHIELD gut microbiome from antibiotic disruption

DAV132, a novel, first-in-class, colon-targeted adsorbent capable of adsorbing a wide range of antibiotics, was well-tolerated in hospitalized elderly patients receiving oral/parenteral fluoroquinolones* (FQs), and protected the intestinal microbiota without influencing the plasma concentration of free FQs, the phase II European SHIELD trial has shown.

“All antibiotics elicit intestinal dysbiosis, causing degraded immunity and immune response, and dysfunctional gut barrier and colonization by opportunistic/pathogenic bacteria such as Clostridioides (C.) difficile,” said presenting author Professor Mark Wilcox from the Leeds Teaching Hospitals & University of Leeds, UK. “[Our study] achieved the primary endpoint; DAV132 is safe for use in hospitalized patients, even with several comorbidities and concomitant medications.”

A total of 243 patients (median age 71 years, 51 percent female) with suspected or documented bacterial infections** were randomized 1:1 to receive FQs with or without DAV132 7.5 g TID for 5–21 days. [ID Week 2020, abstract LB-5]

The percentages of patients reporting adverse events (AEs) were similar regardless of the presence (15 percent) or absence (11 percent) of DAV132. No serious AEs were reported.

Secondary outcomes

There was no difference in the frequency of infection resolution across all FQs, regardless of the presence or absence of DAV132, noted Wilcox. “[This suggests that] DAV132 captures FQs in the colon without impacting their plasma concentration nor clinical response to the antibiotic treatments.”

End-of-FQ treatment saw marked reductions in faecal concentrations of free FQs (>97 percent; p<0.0001 for all FQs) and VRE*** counts (p=0.019) with DAV132.

Baseline Shannon diversity index was maintained with DAV132, both at day 6 (p=0.006) and end-of-FQ treatment (p=0.03). These findings imply that DAV132 significantly preserved the diversity of the intestinal microbiome from FQ-induced disruption, noted Wilcox.

Moreover, as per CRACS^#, quantitative ex vivo proliferation of C. difficile in stools at end-of-FQ treatment was greater without DAV132 (p=0.035). This illustrates the ability of DAV132 to preserve resistance to C. difficile colonization, thus underlining its protective potential against antibiotic-induced C. difficile infection (CDI).

A promise in a tiny package

DAV132 adsorbents are packed as tiny beads/pellets that are coated for targeted delivery of the adsorbent core to the lower gastrointestinal tract, Wilcox explained. These were designed to be co-administered with any antibiotic from any class to protect the intestinal microbiota and consequently prevent degraded immunity, opportunistic infections, and antibiotic-induced disruption of the gut microbiome, he added.

“[Taken together, our findings suggest that] DAV132 is a promising novel product to prevent antibiotic-induced intestinal dysbiosis,” said Wilcox.

While the trial was not powered to demonstrate the efficacy of DAV132 against CDI and AAD^##, the incidences of CDI and AAD were low among those receiving (n=0 and 2, respectively) and not receiving DAV132 (n=0 and 5, respectively). “[These were] lower than expected,” said Wilcox. Also, the null incidence of CDI may be due to the low C. difficile carriage rate at baseline (2.5 percent). “We [will] aim for patients with higher CDI risk in a pivotal clinical trial [to] confirm its clinical efficacy,” he added.