DAV132 - Combating Resistance Amplification
Concept
DAV132 compound is developed as a novel class of products to be used in combination with antibiotics. It has two clinical objectives:
- Decrease significantly side effects of current antibiotics for patients under treatment ;
- Prevent emergence and dissemination of resistance in the commensal flora, therefore minimizing nosocomial infections in hospital settings as well as in the community, and prolonging the life span of novel antibiotics.
Mechanism of action
Discover the DAV132 mechanism of action in the following video:
The majority of orally administered antibiotics are only partially absorbed and for some of them, a significant part of the administered drug (depending on the antibiotic) remains intact in the intestinal tract. The outcome is similar for intramuscular or intravascular administered antibiotics that are recycled via the hepatobiliary route from the blood into the small intestine.
After antibiotic intakes, active residues progress to the colon, at doses that are orders of magnitude higher than the MIC (minimum inhibitory concentration) for most commensal bacteria. These residues provoke serious collateral damage amongst the commensal flora of patients. The microbiota balance is disturbed: resistant strains are selected; large bacterial populations are erased whereas some strains proliferate. The patient microbiota will take months to recover.
DAV132 is a non specific adsorbent which can irreversibly capture antibiotics in the late ileum, caecum and colon before they could alter significantly the microbiota. It is encapsulated in a specific drug delivery system (specific coating) patented by Da Volterra that allows a precise delivery to the lower gastro-intestinal tract in order to avoid all interactions with drug absorption that occurs in the small intestine.
Development status
Da Volterra has completed the optimization of its drug candidate, the preclinical evaluation of its product in animal studies and is almost done with the pre-IND studies. The clinical development of DAV132 is due to start in Q3 2012.
Publications
- Andremont, A. (2003). Commensal Flora May Play Key Role in Spreading Antibiotic Resistance. ASM news , 69 (12), 601-607.
- Baquero, F., Coque, T. M., & la, F. d. (2011). Ecology and evolution as targets: the need for novel eco-evo drugs and strategies to fight antibiotic resistance. Antimicrob Agents Chemother , 55 (8), 3649-3660.
- Fantin, B., Duval, X., Massias, L., Alavoine, L., Chau, F., Retout, S., et al. (2009). Ciprofloxacin Dosage and Emergence of Resistance in Human Commensal Bacteria. J.Infect.Dis. , 200 (3), 390-398.
- Nguyen TT; Chachaty E; Huy C; Mentre F; de Gunzburg J, Andremont A (2011), Correlation between counts of ciprofloxacin resistant enterobacteriaceae and ciprofloxacin concentrations in feces during treatment, Poster ICAAC Chicago, A1-1749.
- Pultz, M., Nerandzic, M., Stiefel, U., & Donskey, C. (2008). Emergence and acquisition of fluoroquinolone-resistant gram-negative bacilli in the intestinal tracts of mice treated with fluoroquinolone antimicrobial agents. Antimicrob.Agents Chemother. , 52 (9), 3457-3460.
- Tarkkanen, A., Heinonen, T., Jogi, R., Mentula, S., der, M. v., Donskey, C., et al. (2009). P1A recombinant beta-lactamase prevents emergence of antimicrobial resistance in gut microflora of healthy subjects during intravenous administration of ampicillin. Antimicrob.Agents Chemother. , 53 (6), 2455-2462.
- Tosh, P. K. & McDonald, L. C. (2012). Infection control in the multidrug-resistant era: tending the human microbiome. Clin Infect Dis 54(5), 707--713.
