LB-5. DAV132 Protects Intestinal Microbiota of Patients Treated with Quinolones, a European Phase II Randomized Controlled Trial (SHIELD)

Abstract

Background. Antibiotics elicit intestinal dysbiosis with short and long-term deleterious effects. A colon-targeted adsorbent, DAV132, prevents dysbiosis in healthy humans and may protect antibiotic-treated patients. Methods. Hospitalized patients receiving oral/iv fluoroquinolones (FQ) for the treatment of or prophylaxis of febrile neutropenia were randomized to receive DAV132 (7.5g tid orally), or not, during FQ receipt and followed up 51d. Plasma FQ levels were assessed at D4 (LC-MS/MS). Feces were collected during and up to 30d after FQ receipt for assessment of free fecal FQ levels (LC-MS/MS), gut microbiome $α$/$β$ diversity (16S rRNA), resistance to colonization by C. difficile (Cd; ex-vivo proliferation). Relatedness of adverse events (AEs) to drugs was adjudicated by blinded independent experts. Results. 243 patients from 23 sites, median age 71y, ≥1 chronic comorbidity 95%, received levofloxacin (43%), ciprofloxacin (40%) or moxifloxacin (18%) for (79% iv). During receipt, fecal FQ levels were lowered by >97% with DAV132 vs. No DAV132 (p< 0.0001), whilst plasma levels did not change significantly. Microbiome diversity was significantly protected with DAV132 using all metrics, e.g. the change from D1 of Shannon index at End-of-FQ (difference of means at End-of-FQ 0.42, 95% CI: 0.085; 0.752). The proportions of patients with DAV132- and/or FQ-related AEs (primary endpoint) did not differ significantly (14.8 vs. 10.8%, difference of proportions: 3.9%; 95% CI: -4.7; 12.6). No Cd infection occurred. Resistance to colonization by Cd was reduced in stools of patients receiving FQ only, but was maintained in those of patients who also received DAV132 (p=0.035). The acquisition of fecal carriage of vancomycin- resistant enterococci (VRE) was reduced with DAV132 (p=0.019). Conclusion. DAV132 was well tolerated in elderly hospitalized patients with comorbidities. It neither altered antibiotic plasma levels nor elicited changes in concomitant drugs regimens. Intestinal microbiota diversity was protected and resistance to colonization by Cd was preserved. DAV132 is a promising, novel product to prevent antibiotic-induced intestinal dysbiosis.