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Antoine Andremont

Publications and source records attributed to Antoine Andremont.

At least 19 recordsLinked to original sources

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs&#x2009;+&#x2009;BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs&#x2009;+&#x2009;BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p&#x2009;<&#x2009;0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗

Evaluation of critical formulation parameters influencing the bioactivity of beta-lactamases entrapped in pectin beads.

The bioactivity of beta-lactamases upon entrapment in calcium-pectinate beads was evaluated. Non-amidated (NAP) and amidated pectin (AP) beads were prepared according to the ionotropic gelation method using calcium chloride (CaCl(2)) as gelling agent, washed and dried at 37 degrees C in an oven for 2h. Both enzyme activity and protein content were determined as well as bead calcium content. NAP allowed a better encapsulation of the protein than AP. Increasing both CaCl(2) concentration and bead residence time in the gelation medium led to a significant loss of beta-lactamase activity. The drying process of beads also lowered the enzyme activity. Moreover, bead calcium content increased as the CaCl(2) concentration augmented. Being very hygroscopic, the excess of CaCl(2) correlates with an increase of moisture content in beads that affects enzyme activity. After elimination of free calcium from beads, it was shown that a small amount is needed to form the Ca-pectinate network and that the activity of beta-lactamases is preserved in these conditions. Therefore, the bioactivity of encapsulated beta-lactamases in pectin beads mainly depends on formulation parameters such as pectin type, CaCl(2) concentration, washing and drying processes.

Calcium↗

Effect of human vicinity on antimicrobial resistance and integrons in animal faecal Escherichia coli.

OBJECTIVES: To determine the level of antimicrobial resistance and the occurrence of class 1, 2 and 3 integrons in faecal Escherichia coli from several animal populations variously exposed to human contact. METHODS: A collection of 341 faecal E. coli isolates was constituted from several animal populations subject to various degrees of exposure to humans: 18 animals never exposed to humans (living in the Antarctic or Gabon), 71 wild animals living in a low human density area (mountainous region of the Pyrenees, France), 61 wild animals living in a higher human density area (Fontainebleau forest near Paris, France), and 128 extensively reared farm animals and 42 pet dogs, both living in the Pyrenees. Resistance to antimicrobial agents was determined by the method of disc diffusion and quantified using the resistance score of BE Murray, JJ Mathewson, HL DuPont, CD Ericsson and RR Reves (Antimicrobial Agents and Chemotherapy 1990; 34: 515-18). Integrons were characterized by triplex real-time PCR and sequencing. The absence of epidemiologic clones was confirmed by PCR-based methods. RESULTS: A gradient of resistance ranging from absence to high prevalence (resistance score of 18.7%) and a gradual increase in the prevalence of class 1 integrons (from 0% to 16%), both correlated with the increase in exposure to humans, were observed. In wild animals with little contact with humans, resistance, when present, was not mediated by integrons. CONCLUSIONS: Our findings firmly establish that the current prevalence of antimicrobial resistance found in animal faecal bacteria, as well as the prevalence of integrons, is clearly anthropogenic. The presence of integrons may constitute an adaptive process to environments whose antimicrobial pressure exceeds a certain threshold.

Animals↗

Acquired gentamicin resistance by permeability impairment in Enterococcus faecalis.

Enterococci are intrinsically resistant to low levels of aminoglycosides. We previously selected in vitro and in vivo Enterococcus faecalis with intermediate-level resistance to gentamicin that did not abolish synergism with a cell-wall-active agent (E. Aslangul et al., Antimicrob. Agents Chemother. 49:4144-4148, 2005). The aim of this study was to investigate the mechanism of resistance to gentamicin in the 1688-G3 third-step mutant (MIC, 512 microg/ml) of E. faecalis JH2-2. No mutations were found in the genes for L6 ribosomal protein and the four copies of 16S rRNA. Production of a known aminoglycoside-modifying enzyme was unlikely due to the distinct resistance phenotype and absence of the corresponding genes. Efflux was also unlikely since ethidium bromide MICs were similar for JH2-2 and 1688-G3 and since the pump inhibitors reserpine and verapamil had no effect on gentamicin resistance in both strains. To study gentamicin accumulation, we developed a nonisotopic method based on a fluorescent polarization immunoassay. Impaired gentamicin accumulation was observed in 1688-G3 compared to JH2-2 and was only partially reversible by the N,N'-dicyclohexylcarbodiimide (DCCD) uncoupler agent. The lower sensitivity of 1688-G3 to DCCD suggested alteration of the FoF1-ATPase. However, no mutations were detected in the structural genes (atp) for the Fo channel and no difference in transcript levels of atpB and atpE was found between 1688-G3 and JH2-2. Our data are compatible with acquisition of intermediate-level gentamicin resistance by uptake impairment in E. faecalis.

Adenosine Triphosphate↗

Successful long-term program for controlling methicillin-resistant Staphylococcus aureus in intensive care units.

OBJECTIVE: To evaluate the effectiveness of screening strategy and contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA). DESIGN AND SETTING: Prospective observational cohort from 1 February 1995 to 31 December 2001 in three intensive care units (45 beds) in a French teaching hospital. PATIENTS: 8,548 patients admitted to the three ICUs had nasal screening on ICU admission and weekly thereafter. Contact precautions were used in MRSA-positive patients. The following variables were collected: age, gender, severity score, length of stay, workload, and colonization pressure (percentage of patient-days with an MRSA to the number of patient-days in the unit). Alcohol-based handrub solution was introduced in July 2000. We compared the period before this (P1) with that thereafter (P2). RESULTS: Of the 8,548 admitted patients 554 (6.5%) had MRSA at ICU admission, and 456 of the 7,515 (6.1%) exposed patients acquired MRSA. Acquisition incidence decreased from 7.0% in P1 to 2.8% in P2. Independent variables associated with MRSA acquisition were: age (adjusted odds ratio 1.013), severity score (1.047), length of ICU stay (1.015), colonization pressure (1.019), medical ICU (1.58), and P2 (0.49). CONCLUSIONS: MRSA control in these ICUs characterized by a high prevalence of MRSA at admission was achieved via multiple factors, including screening, contact precautions, and use of alcoholic handrub solution. Our results after adjustment of risk factors for MRSA acquisition and the steady improvement in MRSA over several years strengthen these findings. MRSA spreading can be successfully controlled in ICUs with high colonization pressure.

Adult↗

In vitro and in vivo evaluation of pectin beads for the colon delivery of beta-lactamases.

The aim of the present study was to provide a "proof of concept" of colon delivery of beta-lactamases by pectin beads aiming to degrade residual beta-lactam antibiotics, in order to prevent the emergence of resistant bacterial strains. Pectin beads were prepared according to ionotropic gelation method using CaCl2 as a gelling agent. Particles were then washed and soaked in polyethylenimine (PEI). Coating beads with PEI considerably improved their stability in simulated intestinal medium. In vitro studies showed that beta-lactamases were released from pectin beads in colonic medium due to the action of pectinolytic enzymes. When ampicillin was added to this medium, the release of beta-lactamases induced, as expected, the antibiotic inactivation. Finally, after oral administration of loaded-beads to CD1 mice, beta-lactamases were retrieved in high concentrations in faeces. Observation by SEM of beads extracted from mice intestinal tracts concluded the core degradation of beads without any modification of the PEI coating layer. This study demonstrates that a multiparticulate system with suitable characteristics for site-specific colonic delivery can be prepared. This system could be used to target beta-lactamases to the colon in order to hydrolyse antibiotic residues during treatment and prevent their impact on colonic microflora.

Animals↗

High prevalence of carriage of methicillin-resistant Staphylococcus aureus at hospital admission in elderly patients: implications for infection control strategies.

BACKGROUND: Despite contact isolation precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA), MRSA infections are increasing in many countries. OBJECTIVE: To evaluate the role of a potential unrecognized reservoir of MRSA carried by patients in acute care wards, we determined the prevalence of MRSA at hospital admission, with special emphasis on screening-specimen yields. SETTING: A 1100-bed teaching hospital in Paris, France. METHODS: Nasal screening cultures were performed at admission to a tertiary-care teaching hospital for patients older than 75 years. RESULTS: MRSA was isolated from 63 (7.9%) of 797 patients. On the multivariate analysis, variables significantly associated with MRSA carriage were presence of chronic skin lesions (adjusted odds ratio [AOR], 5.10; 95% confidence interval [CI95], 2.52-10.33); transfer from a nursing home, rehabilitation unit, or long-term-care unit (AOR, 4.52; CI95, 2.23-9.18); and poor chronic health status (AOR, 1.80; CI95, 1.02-3.18). Without admission screening, 84.1% of MRSA carriers would have been missed at hospital admission and 76.2% during their hospital stay. Furthermore, 81.1% of days at risk for MRSA dissemination would have been spent without contact isolation precautions had admission screening not been performed. CONCLUSIONS: MRSA carriage at hospital admission is far more prevalent than MRSA-positive clinical specimens. This may contribute to failure of contact isolation programs. Screening cultures at admission help to identify the reservoir of unknown MRSA patients.

Aged↗

Relationship between the level of acquired resistance to gentamicin and synergism with amoxicillin in Enterococcus faecalis.

In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 < MIC < 500 microg/ml), we selected in vitro three consecutive generations of mutants of Enterococcus faecalis JH2-2 with MICs of gentamicin at 128 microg/ml for G1-1477, 256 microg/ml for G2-1573, and 512 microg/ml for G3-1688. E. faecalis 102, which is highly resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 microg/ml (1/16th the MIC), 16 microg/ml (one-eighth the MIC), 64 microg/ml (one-quarter the MIC), and 256 microg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P < 0.05) but not in those infected with the strains G3-1688 and 102. Thus, intermediate levels of resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 microg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.

Amoxicillin↗

Integron-associated antibiotic resistance and phylogenetic grouping of Escherichia coli isolates from healthy subjects free of recent antibiotic exposure.

The study of integrons in 181 Escherichia coli isolates from three groups of healthy subjects who lived in communities and had not taken antibiotics for at least 1 month showed that the presence of integrons was associated with antibiotic resistance and phylogenetic grouping of the bacterial host and dependent on a subject's living environment.

Anti-Bacterial Agents↗

Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia.

Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models. The 14-day mortality was not significantly different for the two groups. However, among critically ill patients, combination antibiotic therapy was associated with lower 14-day mortality (23.4 versus 55.3%, p = 0.0015). This improvement in survival was independent of country of origin, intensive care unit support, class of antibiotics, or in vitro activity of the antibiotics prescribed. Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness.

Adolescent↗

Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity.

A matched case-control study was performed to identify risk factors for acquiring multidrug-resistant Pseudomonas aeruginosa (MDRPA) in intensive care unit (ICU) patients during a 2-year period. MDRPA was defined as P. aeruginosa with combined decreased susceptibility to piperacillin, ceftazidime, imipenem, and ciprofloxacin. Thirty-seven patients who were colonized or infected with MDRPA were identified, 34 of whom were matched with 34 control patients who had cultures that showed no growth of P. aeruginosa. Matching criteria were severity of illness and length of ICU stay, with each control patient staying in the ICU for at least as long as the time period between the corresponding case patient's admission to the ICU and the acquisition of MDRPA. Baseline demographic and clinical characteristics and the use of invasive procedures were similar for case patients and control patients. Multivariate analysis identified duration of ciprofloxacin treatment as an independent risk factor for MDRPA acquisition, whereas the duration of treatment with imipenem was of borderline significance. These data support a major role for the use of antibiotics with high antipseudomonal activity, particularly ciprofloxacin, in the emergence of MDRPA.

Aged↗

Antimicrobial resistance in commensal flora of pig farmers.

We assessed the quantitative contribution of pig farming to antimicrobial resistance in the commensal flora of pig farmers by comparing 113 healthy pig farmers from the major French porcine production areas to 113 nonfarmers, each matched for sex, age, and county of residence. All reported that they had not taken antiimicrobial agents within the previous month. Throat, nasal, and fecal swabs were screened for resistant microorganisms on agar containing selected antimicrobial agents. Nasopharyngeal carriage of Staphylococcus aureus was significantly more frequent in pig farmers, as was macrolide resistance of S. aureus from carriers. Nongroupable streptococci from the throat were more resistant to the penicillins in pig farmers. The intestinal isolation of enterococci resistant to erythromycin or vancomycin was not significantly higher in pig farmers in contrast to that of enterobacteria resistant to nalidixic acid, chloramphenicol, tetracycline, and streptomycin. Prevalence of resistance in predominant fecal enterobacteria was also significantly higher in pig farmers for cotrimoxazole, tetracycline, streptomycin, and nalidixic acid. We determined a significant association between pig farming and isolation of resistant commensal bacteria.

Adult↗

Antibacterial resistance, Wayampis Amerindians, French Guyana.

Drug resistance in fecal bacteria was high in Wayampis Amerindians who did not take antibacterial agents and were not hospitalized for 1 year. In the Wayampis Amerindians, an isolated traditional community in French Guyana, antibacterial use was 0.64 treatments per person per year. Hospitalization rate was 6.1% per year. Antibacterial drug-resistant bacteria can spread in persons who are not taking antibacterial agents.

Adolescent↗

An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome.

We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.

Adolescent↗

The stenlying effect of high hydrostatic pressure on thermally and hydrolytically labile nanosized carriers.

PURPOSE: To investigate whether high hydrostatic pressure (HHP) treatment allows the sterilization of thermosensitive polymer nanoparticle suspensions without jeopardizing their physicochemical integrity. METHODS: Application of HHP was explored on a wide variety of thermosensitive poly(cyanoacrylate) nanoparticles, varying by their type (nanospheres or nanocapsules), by their preparation method (nanoprecipitation or emulsion/solvent evaporation), as well as by their surface characteristics. Physicochemical characterization before and after pressurization included turbidimetry, size measurement, zeta potential, scanning electron microscopy and infrared analysis. A sterility test also conducted according to pharmacopoeial requirements on an importantly contaminated nanoparticle suspension. RESULTS: Poly(cyanoacrylate) nanoparticles appeared to be extremely baroresistant. Continuous or oscillatory HHP treatment up to 500 MPa during 30 min induced generally neither physical, nor chemical damage. However, precautions should be taken when surface modifiers are adsorbed onto nanoparticles, as a layer destabilization may occur. Finally, this process allowed the successful inactivation of vegetative bacteria, yeast, and fungi. CONCLUSIONS: This work proposes HHP as a new method for polymer drug carriers sterilization, taking into account that further exploration in this area is needed to propose novel protocols for spores inactivation.

Chemistry, Pharmaceutical↗