OASIS evaluation of the French surveillance network for antimicrobial resistance in diseased animals (RESAPATH): success factors underpinning a well-performing voluntary system.

Antimicrobial resistance is a One Health issue requiring the development of surveillance systems in the human, environmental and animal sectors. In the European Economic Area, the surveillance of antimicrobial resistance in zoonotic pathogens and indicator bacteria in healthy food-producing animals is required legally, while countries are also expected to extend their surveillance to diseased animals in the frame of national action plans. In this context, evaluating existing antimicrobial resistance surveillance systems in animal health is important to improve systems in place, but also to help other countries learn from these experiences, understand success factors and anticipate challenges. With this aim, the French surveillance network for antimicrobial resistance in bacteria from diseased animals (RESAPATH) was evaluated using the Outil d'Analyse des Systèmes d'Information en Santé (OASIS) assessment tool. Key performance factors included (i) a strong and inclusive central institutional organisation defining clear and well-accepted surveillance objectives, scope and procedures, (ii) strong skills in epidemiology and microbiology and (iii) a win-win approach enabling the voluntary participation of 71 field laboratories and where free annual proficiency testing plays a pivotal role. The main area for improvement of RESAPATH was its time-consuming data management system.

Effects of antimicrobial exposure on the antimicrobial resistance of Escherichia coli in the digestive flora of dairy calves.

Veal calves are often identified as reservoirs for antimicrobial resistant Escherichia coli (E. coli). This production is closely linked with dairy production, as young calves - mostly males - are collected from dairy farms to enter the fattening process. The aim of this prospective study was to explore the factors on dairy farms that favour the selection of antimicrobial resistance (AMR) in the digestive E. coli strains of young calves and to assess whether the resistance levels and selection pressure were the same for males and females. The exposure of calves to antimicrobials was investigated through three factors: antimicrobial treatment of calves; feeding of calves with milk from cows treated with antimicrobials; and the consumption of colostrum from cows treated with antimicrobials at dry-off. The study design involved 100 dairy farms. A calf of each sex was selected from birth on each farm. Information on the calves' exposure to antimicrobials was collected daily and calves were sampled (rectal swab) two weeks after birth, then seven weeks after birth for females only. Laboratory analyses included culture on two distinct media: a non-selective medium (identifying dominant flora) and a medium containing ceftiofur to select the extended-spectrum beta-lactamase (ESBL) phenotype. Susceptibility testing was performed on an E. coli strain from each medium. Generalised linear models were used to assess associations between the resistance of E. coli strains and antimicrobial exposure. A set of 280 swabs from healthy calves were analysed. In dominant flora, high levels of resistance (>60 %) were identified for streptomycin, tetracycline and amoxicillin but AMR levels were low (3 %) for critically important antimicrobials (3rd- and 4th-generation cephalosporins and fluoroquinolones). For females staying in dairy farms, a marked decrease in resistance was observed for almost all antimicrobials between the age of 15 days and 7 weeks. A selective medium revealed an ESBL phenotype for 20.7 % of the calves. Whether for AMR or antimicrobial exposure, no significant difference was found between male and female calves. The antimicrobial treatment of calves was associated with an increased resistance of E. coli from dominant flora for amoxicillin (OR = 2.9), gentamicin (OR = 4.6), florfenicol (OR = 5.0) and trimethoprim-sulfonamide (OR = 5.6). The consumption by calves of milk from cows treated with antimicrobials was also associated with an increased resistance to amoxicillin (OR = 2.6), gentamicin (OR = 4.0), tetracycline (2.6) and trimethoprim-sulfonamide (OR = 2.2). In contrast, the models did not reveal any association between AMR and consumption of colostrum from cows treated with antimicrobials at dry-off.

Antimicrobial resistance in bacteria isolated from diseased horses in France.

BACKGROUND: Horses are one of the potential reservoirs of antimicrobial resistance (AMR) determinants that could be transferred to human subjects. OBJECTIVE: To describe the AMR patterns of major bacteria isolated from diseased horses in France. STUDY DESIGN: Retrospective observational study. METHODS: Data collected between 2012 and 2016 by RESAPATH, the French national surveillance network for AMR, were analysed. Only antimicrobials relevant in veterinary and human medicine for the isolated bacteria were considered. Mono- and multidrug resistance were calculated. The resistance proportions of major equine diseases were assessed and compared. Where data permitted, resistance trends were investigated using nonlinear analysis (generalised additive models). RESULTS: A total of 12,695 antibiograms were analysed. The five most frequently isolated bacteria were Streptococcus spp., Escherichia coli, Pseudomonas spp., Staphylococcus aureus, Pantoea spp. and Klebsiella spp. The highest proportions of resistance to gentamicin were found for S. aureus (22.1%) and Pseudomonas spp. (26.9%). Klebsiella spp. and E. coli had the highest proportions of resistance to trimethoprim-sulfamethoxazole (15.5 and 26.2%, respectively). Proportions of resistance to tetracycline were among the highest for all the bacteria considered. Resistance to third-generation cephalosporins was below 10% for all Enterobacteriaceae. The highest proportions of multidrug resistance (22.5%) were found among S. aureus isolates, which is worrying given their zoonotic potential. From 2012 to 2016, resistance proportions decreased in Pseudomonas spp. isolates, but remained the same for S. aureus. For Streptococcus spp. and E. coli, resistance proportions to trimethoprim-sulfamethoxazole increased. MAIN LIMITATIONS: Since antibiograms are not systematic analyses, any selection bias could impact the results. CONCLUSIONS: Such studies are essential to estimate the magnitude of the potential threat of AMR to public health, to design efficient control strategies and to measure their effectiveness. These findings may also guide the initial empirical treatment of horse diseases.

Antimicrobial resistance patterns of bacteria isolated from dogs with otitis.

Antimicrobial-resistant bacteria in dogs can be transmitted to humans and close contact between dogs and people might foster dissemination of resistance determinants. The aim of our study was to describe the antimicrobial resistance (AMR) pattern of the major causative agents of canine otitis - one of the most common diseases in dogs - isolated in France. Data collected between 2012 and 2016 by the French national surveillance network for AMR, referred to as RESAPATH, were analysed. Resistance trends were investigated using non-linear analysis (generalised additive models). A total of 7021 antibiograms were analysed. The four major causative agents of canine otitis in France were coagulase-positive staphylococci, Pseudomonas aeruginosa, Proteus mirabilis and streptococci. Since 2013, resistance to fluoroquinolones has been on the decrease in both P. aeruginosa and Staphylococcus pseudintermedius isolates. For P. aeruginosa, 19.4% of isolates were resistant to both enrofloxacin and gentamicin. The levels of multidrug resistance (acquired resistance to at least one antibiotic in three or more antibiotic classes) ranged between 11.9% for P. mirabilis and 16.0% for S. pseudintermedius. These results are essential to guide prudent use of antibiotics in veterinary medicine. They will also help in designing efficient control strategies and in measuring their effectiveness.

Antimicrobial resistance trends in Escherichia coli isolated from diseased food-producing animals in France: A 14-year period time-series study.

Antimicrobial resistance (AMR) among bacteria isolated from food-producing animals is a growing concern with implications for public health. AMR surveillance is essential to identify resistance trends and help in the design of effective and efficient control strategies. The aim of the study was to describe the antimicrobial susceptibility of pathogenic Escherichia coli isolated from three livestock productions in France (cattle, swine and poultry). The trend in resistance to the most commonly prescribed antibiotics in animal health was analysed as follows: amoxicillin (penicillin), spectinomycin or streptomycin (aminoglycoside), tetracycline and trimethoprim-sulfamethoxazole/Enrofloxacin and ceftiofur were also taken into account as members of critically important antimicrobial families in human and veterinary medicine, that is fluoroquinolones and third-generation cephalosporins, respectively. Data collected between 2002 and 2015 by the French national surveillance network of AMR referred to as RESAPATH were analysed. Resistance trends were investigated using non-linear analysis (generalized additive models) applied to time-series stratified by livestock production and antibiotic. Irrespective of the species and the antibiotic considered, resistance signals over time showed no significant annual cycle. Resistance to third-generation cephalosporins emerged during the period of the study, with a peak at 22% [20.5; 24.0] in poultry in 2010, decreasing afterwards, while it remained consistently below 10% for the other species. The proportion of resistance to fluoroquinolones was broadly similar between species and remained under 30%, with a slight decreasing trend after 2009. Resistances to tetracycline and amoxicillin remained high, between 90% and 40% over time in cattle and swine. After 2010, there was a decrease in resistance to these antibiotics for all species, especially to tetracycline for poultry with a drop from 84% in 2009 to 43% in 2015. These results contribute to risk assessment and constitute objective evidence on which to evaluate the efficacy of control measures implemented to limit AMR occurrence.

Quantitative and qualitative analysis of antimicrobial usage in white veal calves in France.

The development of antimicrobial resistance has made it necessary to measure antimicrobial usage in animal production sectors. France is a major European producer of white veal calves, but few data were previously available for that sector, even though these young animals are particularly susceptible to infection and considered as a reservoir of antimicrobial resistance. A cross-sectional study was conducted on 186 batches of French calves to estimate the exposure of white veal calves to antimicrobials and identify the potential risk factors related to antimicrobial usage. An indicator of calf exposure was calculated as a count of the number of antimicrobial treatments per calf. The indicator was based on veterinary prescriptions (products, quantity dispensed and dosage prescribed) and the estimated weight of calves at treatment, using the dates of treatment collected from farm registers. The study showed that calves were exposed to an average of 8.55 antimicrobial treatments (SD: 2.21, range: 2.75-15.86) over the five to six months of the fattening process. Group treatments were predominant (95.8%) and administered by the oral route. The "starting treatments", given during the first two weeks of the fattening period, were administered systematically (to all the calves in all the farms) and accounted for a third of all treatments. Tetracyclines, polypeptides and macrolides were the most widely used antimicrobials, with respectively 4.32, 1.59 and 1.01 treatments per calf. Only rare uses of 3rd and 4th generation cephalosporins and fluoroquinolones, considered as critically important in human medicine, were reported. Despite low variability of exposure between farms, a linear mixed-effects model highlighted a higher variability between farmers (ICC=0.14) or veterinarians (ICC=0.12), than between integrators (ICC=0.06). The number of calves per pen, introduced as a fixed effect in the model, was also significant: calves housed in pens of 6-10 and fed in buckets had on average 2.55 more antimicrobial treatments per calf than calves housed in pairs with the same feeding system. The model also highlighted an increase of 1.48 treatments per calf for farms with more than five percent of mortality, versus those with two percent or less. The present study showed that antimicrobial treatments are numerous in veal calf fattening farms, particularly at the arrival of the animals. Taking into account the development of resistance to antimicrobials, the necessity and the effectiveness of some of these treatments should be re-evaluated.

Numerical simulations of a buoyant autocatalytic reaction front in tilted Hele-Shaw cells.

We present a numerical analysis of solutal buoyancy effects on the shape and the velocity of autocatalytic reaction fronts, propagating in thin tilted rectangular channels. We use two-dimensional (2D) lattice Bathnagar-Gross-Krook (BGK) numerical simulations of gap-averaged equations for the flow and the concentration, namely a Stokes-Darcy equation coupled with an advection-diffusion-reaction equation. We do observe stationary-shaped fronts, spanning the width of the cell and propagating along the cell axis. We show that the model accounts rather well for experiments we performed using an Iodate Arsenous Acid reaction propagating in tilted Hele-Shaw cells, hence validating our 2D modelization of a three-dimensional problem. This modelization is also able to account for results found for another chemical reaction (chlorite tetrathionate) in a horizontal cell. In particular, we show that the shape and the traveling velocity of such fronts are linked with an eikonal equation. Moreover, we show that the front velocity varies nonmonotonically with the tilt of the cell, and nonlinearly with the width of the cell.

Lock-exchange experiments with an autocatalytic reaction front.

A viscous lock-exchange gravity current corresponds to the reciprocal exchange of two fluids of different densities in a horizontal channel. The resulting front between the two fluids spreads as the square root of time, with a diffusion coefficient reflecting the buoyancy, viscosity, and geometrical configuration of the current. On the other hand, an autocatalytic reaction front between a reactant and a product may propagate as a solitary wave, namely, at a constant velocity and with a stationary concentration profile, resulting from the balance between molecular diffusion and chemical reaction. In most systems, the fluid left behind the front has a different density leading to a lock-exchange configuration. We revisit, with a chemical reaction, the classical situation of lock-exchange. We present an experimental analysis of buoyancy effects on the shape and the velocity of the iodate arsenous acid autocatalytic reaction fronts, propagating in horizontal rectangular channels and for a wide range of aspect ratios (1/3 to 20) and cylindrical tubes. We do observe stationary-shaped fronts, spanning the height of the cell and propagating along the cell axis. Our data support the contention that the front velocity and its extension are linked to each other and that their variations scale with a single variable involving the diffusion coefficient of the lock-exchange in the absence of chemical reaction. This analysis is supported by results obtained with lattice Bathnagar-Gross-Krook (BGK) simulations Jarrige et al. [Phys. Rev. E 81, 06631 (2010)], in other geometries (like in 2D simulations by Rongy et al. [J. Chem. Phys. 127, 114710 (2007)] and experiments in cylindrical tubes by Pojman et al. [J. Phys. Chem. 95, 1299 (1991)]), and for another chemical reaction Schuszter et al. [Phys. Rev. E 79, 016216 (2009)].

[180 aorto-bifemoral bypasses for chronic occlusive arteritis]. / Réflexions à propos de 180 pontages aorto-bifémoraux pour artéritechronique oblitérante.

In the authors' experience, 180 aorto-bifemoral by-pass grafts represent 42.4% of all reconstructive operations for aorto-iliac atheromatous disease performed between 1st January 1972 and 1st July 1983. 37% of the patients presented a threatened amputation and 38.8% had a walking distance of less than 100 metres. The immediate post-operative mortality (1st month) was 2.2% (4 patients). The 5 year survival, expressed according to the actuarial method, was 89% and the patency was 91%. The long-term functional deterioration was due to a progressive alteration of the distal vascular bed and to complications: false aneurysms (2.2%), prosthetic infections (1%), aorto-intestinal fistulae (2.2%), thrombosed prostheses (7.3%). 7 complementary femoro-popliteal by-pass grafts (4%) and 13 major amputations (7.4%) were required. The authors stress the value of performing end-to-end aortic anastomoses rather than side-to-end anastomoses. The anastomoses should be well isolated from the gastrointestinal tract. The patients should be rigorously followed post-operatively and any complication detected should be treated actively.