Oral DAV131, a Charcoal-Based Adsorbent, Inhibits Intestinal Colonization by β-Lactam-Resistant Klebsiella pneumoniae in Cefotaxime-Treated Mice

Abstract

f Antibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistant Klebsiella pneumoniae strain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 10 6 CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (P < 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (P < 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

Impact of Fluoroquinolones on Human Microbiota. Focus on the Emergence of Antibiotic Resistance

“…Yet, before this occurs, we hope to see more successful ways of limiting the impact of antibiotics on microbiota, and not only concerning FQ, such as charcoal-based coating techniques to limit the impact of antibiotics in the proximal colon. The proof of concept has been made and clinical studies have recently begun [85,86]. Closer down the line, FMT may also be an alternative treatment for subjects colonized with multi resistant organisms and suffering recurring infections.…”

“…For example, the use of an enteric-coated formulated activated-charcoal-based products meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon have been proven effective in limiting colonization by strains of cefotaxime-resistant Klebsiella spp. in a mouse model of gut colonization [85]. In human volunteers, these products have recently shown that they can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine [86].…”

Microbiome Disturbances and Autism Spectrum Disorders

“…Consequently, activated charcoal may be useful in microbe-induced neurobehavioral disorders, including ASD. A few studies suggest activated charcoal suppresses the growth of antibiotic-resistant intestinal bacteria (Khoder et al, 2010;Grall et al, 2013). However, similar to antibiotic treatments, it is likely that any beneficial effects of this intervention will be short-lived, and disease symptomology will return upon cessation of this therapy.…”

Sept questions autour du microbiote intestinal et de la résistance aux antibiotiques

“…Les résultats obtenus par les équipes mobiles d'antibiothérapie montrent notamment, en parallèle d'une moindre fréquence de portage de bactéries multirésistantes, une réduction du risque d'infections à Clostridium difficile, ce qui souligne indirectement que l'impact global sur le microbiote intestinal des sujets hospitalisés a été diminué [24]. À moyen terme, l'inactivation de l'antibiotique au niveau du côlon par un adsorbant [25] ou une bêtalactamase [26] est également une stratégie de préservation du microbiote intestinal. Enfin, si la transplantation fécale a montré chez l'animal [27], voire chez l'homme, [28] son efficacité à diminuer les densités intestinales des bactéries multirésistantes, sa mise en oeuvre reste complexe et soulève la question de son innocuité [29].…”