Adsorbent drug may help shield microbiome from antibiotics' ill effects

Last Updated: 2017-12-13

By Reuters Staff

NEW YORK (Reuters Health) - An experimental product based on activated charcoal may help protect the gut microbiome from disruption by antibiotics, a phase 1 randomized trial suggests.

"DAV132 was highly effective to protect the gut microbiome of moxafloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments," Dr. Jean de Gunzburg of Da Volterra in Paris, the company developing DAV132, and colleagues report in Journal of Infectious Diseases, online November 23.

Orally administered antibiotics cause dysbiosis when they reach the cecum and colon, promoting Clostridium difficile infection, diarrhea and the growth of antibiotic-resistant bacteria, Dr. de Gunzburg and his colleagues note. They developed DAV132, which delivers the non-specific adsorbent activated charcoal to the late ileum, and showed in a pilot study that the experimental treatment did not affect plasma pharmacokinetics of a single dose of amoxicillin.

In the new study, 28 healthy volunteers receiving a five-day course of moxafloxacin (MXF) were randomized to receive DAV132 or placebo three times a day. Dr. de Gunzburg and colleagues also included two control groups of eight people each who received DAV132 only or placebo.

Peak free MXF in the placebo group was 136.2 micrograms/gram at day six, while MXF was undetectable by day 16. In patients who received DAV132, fecal free MXF ranged from 1 to 14 micrograms/gram feces per day, up to the sixth day of the study.

Plasma concentrations of MXF were similar in the two groups at day one and day five. One adverse effect occurred, a vulvovaginal mycotic infection that may have been related to MXF, but no DAV132-related adverse effects were observed.

Microbial richness had dropped to 54.6% of baseline by day 6 in volunteers who did not receive DAV132, and still did not return to baseline levels by day 37. At day 6, patients who took DAV132 along with MXF had 97.8% of their baseline microbial richness, similar to the effect in control patients who did not receive MXF. Microbial richness returned to baseline levels 11 days after the end of treatment in the DAV132 group.

One-third of the 252 metagenomic species (MGS) identified in volunteers' guts were altered in the patients who did not receive DAV132. Administering DAV132 protected 81% of the MGS affected by MXF, and partially protected 12%. All of the 34 MGS associated with microbiome richness were protected.

In ex vivo tests of DAV132 against 14 routinely used antibiotics, 13 were at least 95% adsorbed, while one, amoxicillin, was 92% adsorbed.

"The results of this phase 1 trial appear promising: DAV132 may constitute a breakthrough product to prevent short- and long-term detrimental effects of antibiotic treatments," Dr. de Gunzburg and his team write. "Further studies are under way to validate the potential of DAV132 in a clinical set-up."

Da Volterra sponsored the trial, and the investigators also received grants from the European Union and BPI France.

Dr. de Gunzburg was not available for an interview by press time.

SOURCE: http://bit.ly/2ymm0dN

J Infect Dis 2017.