A modelling framework to characterize the impact of antibiotics on the gut microbiota diversity.

Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route).

A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have considerably improved patient outcomes in various cancer types, but their efficacy remains poorly predictable among patients. The intestinal microbiome, whose balance and composition can be significantly altered by antibiotic use, has recently emerged as a factor that may modulate ICI efficacy. The objective of this systematic review and meta-analysis is to investigate the impact of antibiotics on the clinical outcomes of cancer patients treated with ICIs.

An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones.

Background: DAV132 (colon-targeted adsorbent) has prevented antibiotic-induced effects on microbiota in healthy volunteers.

Objectives: To assess DAV132 safety and biological efficacy in patients.

Patients And Methods: An open-label, randomized [stratification: fluoroquinolone (FQ) indication] multicentre trial comparing DAV132 (7.

Microbiota-based markers predictive of development of Clostridioides difficile infection.

Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset.

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics.

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3/4 generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.

Spare and repair the gut microbiota from antibiotic-induced dysbiosis: state-of-the-art.

Homeostasis of the intestinal microbiota is currently recognized as a major contributor to human health. Furthermore, intestinal dysbiosis is associated with a multitude of consequences, including intestinal colonization by antibiotic-resistant or pathogenic bacteria, such as Clostridioides difficile, and reduced efficacy of promising anticancer immunotherapies. By far, the most immediate and drastic exposure leading to dysbiosis is antibiotic treatment.

A Colon-Targeted Adsorbent (DAV132) Does Not Affect the Pharmacokinetics of Warfarin or Clonazepam in Healthy Subjects.

DAV132 is a novel colon-targeted adsorbent that prevents the deleterious impact of antibiotics on gut microbiota without modifying their systemic availability. A randomized, Latin-square crossover, open-label trial with 2 substudies in 18 and 24 healthy volunteers evaluated the pharmacokinetic (PK) bioequivalence of warfarin, a drug with a narrow therapeutic index (NTI), and clonazepam, both widely used for the treatment of chronic conditions, with or without coadministration of DAV132 7.5 g.

Optimization of an Assay To Determine Colonization Resistance to Clostridioides difficile in Fecal Samples from Healthy Subjects and Those Treated with Antibiotics.

A healthy, intact gut microbiota is often resistant to colonization by gastrointestinal pathogens. During periods of dysbiosis, however, organisms such as can thrive. We describe an optimized colonization resistance assay for in stool (CRACS) and demonstrate the utility of this assay by assessing changes in colonization resistance following antibiotic exposure.

Modeling the Effect of DAV132, a Novel Colon-Targeted Adsorbent, on Fecal Concentrations of Moxifloxacin and Gut Microbiota Diversity in Healthy Volunteers.

To prevent antibiotic-induced perturbations on gut microbiota, DAV132, a novel colon-targeted adsorbent, which sequesters antibiotic residues in the lower gastrointestinal tract, was developed. We built an integrated pharmacological model of how DAV132 reduces fecal free moxifloxacin and preserves gut microbiota. We used plasma and fecal free moxifloxacin concentrations, and Shannon diversity index from 16S ribosomal RNA gene metagenomics analysis of fecal microbiota, of 143 healthy volunteers assigned randomly to receive moxifloxacin only, or with 10 DAV132 dose regimens, or to a control group.

NSCLC Immunotherapy Efficacy and Antibiotic Use: A Systematic Review and Meta-Analysis.

Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic-induced disruption of the microbiota may impact ICI efficacy. We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI.

Impact of oral amoxicillin and amoxicillin/clavulanic acid treatment on bacterial diversity and β-lactam resistance in the canine faecal microbiota.

Background: Aminopenicillins with or without a β-lactamase inhibitor are widely used in both human and veterinary medicine. However, little is known about their differential impact on the gut microbiota and development of antimicrobial resistance.

Objectives: To investigate changes in the faecal microbiota of dogs treated with amoxicillin or amoxicillin/clavulanic acid.

DAV131A Protects Hamsters from Lethal Infection Induced by Fluoroquinolones.

Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota, resulting in loss of resistance to colonization by exogenous bacteria such as that may cause severe diarrhea in humans and lethal infection in hamsters. We show here that DAV131A, a charcoal-based adsorbent, decreases the intestinal levels of the fluoroquinolone antibiotics levofloxacin and ciprofloxacin in hamsters, protects their intestinal microbiota, and prevents lethal infection by .

Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection.

Antibiotic disruption of the intestinal microbiota favors colonization by Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis and quantified the link between this intensity and mortality. We administered either moxifloxacin ( = 70) or clindamycin ( = 60) to hamsters by subcutaneous injection from day 1 (D) to D and challenged them with a toxigenic strain at D Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D and D using diversity indices determined from 16S rRNA gene profiling.

Protection of the Human Gut Microbiome From Antibiotics.

Background: Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.

Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis.

Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D] to D) were orally infected at D with spores.

Removal of antibiotics in wastewater by enzymatic treatment with fungal laccase - Degradation of compounds does not always eliminate toxicity.

In this study, the performance of immobilised laccase (Trametes versicolor) was investigated in combination with the mediator syringaldehyde (SYR) in removing a mixture of 38 antibiotics in an enzymatic membrane reactor (EMR). Antibiotics were spiked in osmosed water at concentrations of 10μg·L(-1) each. Laccase without mediator did not reduce the load of antibiotics significantly.

Mathematical modeling of bacterial kinetics to predict the impact of antibiotic colonic exposure and treatment duration on the amount of resistant enterobacteria excreted.

Fecal excretion of antibiotics and resistant bacteria in the environment are major public health threats associated with extensive farming and modern medical care. Innovative strategies that can reduce the intestinal antibiotic concentrations during treatments are in development. However, the effect of lower exposure on the amount of resistant enterobacteria excreted has not been quantified, making it difficult to anticipate the impact of these strategies.

Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects.

During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter.

Identification of new transformation products during enzymatic treatment of tetracycline and erythromycin antibiotics at laboratory scale by an on-line turbulent flow liquid-chromatography coupled to a high resolution mass spectrometer LTQ-Orbitrap.

This work describes the formation of transformation products (TPs) by the enzymatic degradation at laboratory scale of two highly consumed antibiotics: tetracycline (Tc) and erythromycin (ERY). The analysis of the samples was carried out by a fast and simple method based on the novel configuration of the on-line turbulent flow system coupled to a hybrid linear ion trap - high resolution mass spectrometer. The method was optimized and validated for the complete analysis of ERY, Tc and their transformation products within 10 min without any other sample manipulation.

Oral DAV131, a charcoal-based adsorbent, inhibits intestinal colonization by β-lactam-resistant Klebsiella pneumoniae in cefotaxime-treated mice.

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.

Correlation between fecal concentrations of ciprofloxacin and fecal counts of resistant Enterobacteriaceae in piglets treated with ciprofloxacin: toward new means to control the spread of resistance?

We assessed in a piglet model the relationship between fecal ciprofloxacin concentrations and ciprofloxacin-resistant Enterobacteriaceae counts. Twenty-nine piglets were orally treated with placebo or with 1.5 or 15 mg ciprofloxacin/kg of body weight/day from day 1 (D1) to D5.