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DAV132, Novel Colon-Targeted Adsorbent, Protects Intestinal Microbiota From Antibiotic-Induced Dysbiosis

The composition of the gut microbiome is easily disrupted by antibiotics, leaving the host susceptible to further infection or other disturbance of gut flora that can lead to both short- and long-term deleterious effects.

The composition of the gut microbiome is easily disrupted by antibiotics, leaving the host susceptible to further infection or other disturbance of gut flora that can lead to both short- and long-term deleterious effects.

To combat antibiotic-induced dysbiosis, investigators overseas have developed a novel product, DAV132, that works as a colon-targeted adsorbent for patients treated with quinolones. Results from the phase 2 SHIELD trial were presented virtually at ID Week 2020.

“The gut microbiota has long been known by clinicians but, until recently, it was not clear how it was intervening in the overall health of individuals. During the last decade, the multiple roles of the microbiota have been unveiled and links with infectious diseases, immunology, oncology, and antimicrobial resistance have been uncovered,” Jean de Gunzburg, PhD, and Antoine Andremont, PhD, both of Da Volterra, the biotechnology company behind DAV132, told Contagion® in emailed comments.

“The SHIELD study is the culmination of this quest for a safe and efficient product to spare the microbiota when patients need antibiotics,” de Gunzburg and Andremont continued. “The overarching goal of the team was to demonstrate that antibiotics (lifesaving drugs) could be used in patients when needed without the detrimental impact on the gut microbiota and its consequences.”

A total of 243 patients from 23 sites, all of whom were hospitalized and receiving oral or intravenous (IV) fluoroquinolones (FQ) for the treatment of or prophylaxis of febrile neutropenia, were randomized to receive 7.5 g of DAV132 orally three times per day at the time of their antibiotic receipt. Participants were followed for up to 51 days.

Investigators measured plasma FQ levels via liquid chromatography with tandem mass spectrometry (LC-MS/MS) at day 4 and collected fecal samples during and up to 30 days after receipt of FQ. The team assessed for free fecal FQ levels (LC-MS/MS), gut microbiome α/β diversity (16S rRNA), and resistance to colonization by Clostridioides difficile.

Median participant age was 71 years with ≥1 chronic comorbidity 95%. Quinolones received included levofloxacin (43%), ciprofloxacin (40%), or moxifloxacin (18%). The primary end point was the proportion of patients who received DAV132 and/or FQ-related adverse events (AEs).

Participant plasma levels did not change significantly with DAV132 vs no DAV132, but fecal FQ levels decreased by >97% with DAV132 vs no DAV132 during FQ receipt. DAV132 also significantly protected microbiome diversity, investigators determined, but the proportion of patients who received DAV132 and/or experienced FQ-related AEs did not differ significantly (14.8 vs. 10.8%, difference of proportions: 3.9%; 95% CI: -4.7; 12.6).

There were no reports of C difficile infection, but patients who received DAV132 with FQ maintained resistance to C difficile colonization (P = .035) compared with patients receiving FQ only. In addition, DAV132 reduced the acquisition of fecal carriage of vancomycin-resistant enterococci (P = .019).

“DAV132 was well tolerated in elderly hospitalized patients with comorbidities. It neither altered antibiotic plasma levels nor elicited changes in concomitant drugs regimens,” investigators concluded. “Intestinal microbiota diversity was protected and resistance to colonization by [C difficile] was preserved. DAV132 is a promising, novel product to prevent antibiotic-induced intestinal dysbiosis.”

Future clinical studies will evaluate DAV132’s role in reducing the risk of C difficile infection, reducing the burden of antimicrobial resistance, reducing the severity of graft-vs-host disease in patients with hematologic malignancies receiving hematopoietic stem cell transplants, and increasing the overall survival of patients with cancer.

“For clinicians, this means that microbiota-protective therapies such as DAV132 are one step closer to the patients’ beds and could provide significant clinical benefits in a variety of pathologies associated with intestinal microbiota disruption,” de Gunzburg and Andremont said.

The study, “DAV132 Protects Intestinal Microbiota of Patients Treated with Quinolones, a European Phase II Randomized Controlled Trial (SHIELD),” was presented virtually at ID Week 2020.