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.

Fallen stock data: An essential source of information for quantitative knowledge of equine mortality in France.

BACKGROUND: Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiological purposes. In France, data from rendering plants are centralised in the Fallen Stock Data Interchange database (FSDI), managed by the French Ministry of Agriculture, while individual equine data are centralised in the French equine census database, SIRE, managed by the French horse and riding institute (IFCE). OBJECTIVES: To evaluate whether the combined use of the FSDI and SIRE databases can provide representative and accurate quantitative information on mortality for the French equine population and to propose enhancements of these databases to improve the quality of the resulting demographic information. STUDY DESIGN: Descriptive study. METHODS: Mortality ratios for the French equine population were calculated per year between 2011 and 2014 and temporal variations in equine mortality modelled during the same period. Survival analyses were performed on a sample of equines traceable in both the FSDI and SIRE databases. RESULTS: Estimates of the annual mortality ratios varied from 3.02 to 3.40% depending on the years. Survival rates of equines 2-years-old and over differed according to breed categories with the highest median age at death for the ponies. The weekly description of mortality highlighted marked seasonality of deaths whatever the category of equines. Modelling temporal variations in equine mortality also brought to light excess mortality. MAIN LIMITATIONS: Insufficient traceability of equines between the two databases. CONCLUSION: The FSDI database provided an initial approach to equine death ratios on a national scale and an original description of temporal variations in mortality. Improvement in the traceability of equines between the FSDI and SIRE databases is needed to enable their combined use, providing a representative description of equine longevity and a more detailed description of temporal variations in mortality.

Syndromic surveillance of abortions in beef cattle based on the prospective analysis of spatio-temporal variations of calvings.

Our objective was to study the ability of a syndromic surveillance system to identify spatio-temporal clusters of drops in the number of calvings among beef cows during the Bluetongue epizootic of 2007 and 2008, based on calving seasons. France was partitioned into 300 iso-populated units, i.e. units with quite the same number of beef cattle. Only 1% of clusters were unlikely to be related to Bluetongue. Clusters were detected during the calving season of primary infection by Bluetongue in 28% (n = 23) of the units first infected in 2007, and in 87% (n = 184) of the units first infected in 2008. In units in which a first cluster was detected over their calving season of primary infection, Bluetongue was detected more rapidly after the start of the calving season and its prevalence was higher than in other units. We believe that this type of syndromic surveillance system could improve the surveillance of abortive events in French cattle. Besides, our approach should be used to develop syndromic surveillance systems for other diseases and purposes, and in other settings, to avoid "false" alarms due to isolated events and homogenize the ability to detect abnormal variations of indicator amongst iso-populated units.

Pilot simulation study using meat inspection data for syndromic surveillance: use of whole carcass condemnation of adult cattle to assess the performance of several algorithms for outbreak detection.

The objective of this study was to assess the performance of several algorithms for outbreak detection based on weekly proportions of whole carcass condemnations. Data from one French slaughterhouse over the 2005-2009 period were used (177 098 slaughtered cattle, 0.97% of whole carcass condemnations). The method involved three steps: (i) preparation of an outbreak-free historical baseline over 5 years, (ii) simulation of over 100 years of baseline time series with injection of artificial outbreak signals with several shapes, durations and magnitudes, and (iii) assessment of the performance (sensitivity, specificity, outbreak detection precocity) of several algorithms to detect these artificial outbreak signals. The algorithms tested included the Shewart p chart, confidence interval of the negative binomial model, the exponentially weighted moving average (EWMA); and cumulative sum (CUSUM). The highest sensitivity was obtained using a negative binomial algorithm and the highest specificity with CUSUM or EWMA. EWMA sensitivity was too low to select this algorithm for efficient outbreak detection. CUSUM's performance was complementary to the negative binomial algorithm. The use of both algorithms on real data for a prospective investigation of the whole carcass condemnation rate as a syndromic surveillance indicator could be relevant. Shewart could also be a good option considering its high sensitivity and simplicity of implementation.

Identifying antimicrobial multiresistance patterns of Escherichia coli sampled from diarrhoeic calves by cluster analysis techniques: a way to guide research on multiresistance mechanisms.

Multiresistance is a critical issue. This study points out the usefulness of cluster analysis techniques to describe concisely the antimicrobial susceptibility patterns of bacterial isolates in a way that could effectively help in generating hypotheses on multiresistance mechanisms. Data were selected from the French antimicrobial resistance survey network on veterinary pathogens (Resapath). They were related to 1545 Escherichia coli isolates, which were isolated from faecal samples of diarrhoeic calves in France between 2002 and 2006. Ten clusters of isolates displaying similar features in terms of resistance profile to 13 relevant antimicrobials were computed. The presence of two to ten simultaneous resistances was detected in nine out of the ten clusters. Looking at potential mechanistic interpretations, results may suggest genetic links between some resistance mechanisms, but this should be confirmed by molecular investigation of the corresponding isolates. Looking at therapeutical potential implications, the high level of resistance and multiresistance to several antimicrobials observed in E. coli makes a critical reassessment of empiric oral antimicrobial therapy in calves highly desirable.

Complementary approach of data analysis and modeling to estimate the pattern of the BSE epidemic: the example of France.

Clinical surveillance was the only way to detect bovine spongiform encephalopathy (BSE) until July 2000 in France. From the 103 cases identified as such between 1991 and June 2000, we used a back-calculation method to reconstruct the longitudinal trend of BSE infections. Between July 1987 and June 1997, an estimated 51,300 (CI =[24,300-84,700]) cattle were infected in France. The comprehensive surveillance of BSE with rapid tests, set up in France since 2001 at the abattoir and fallen plant, allowed study of the relative exposure of the successive birth cohorts with nonconditional logistic regression models adjusted for possible confounding variables. The results were in agreement with those of the back-calculation model, estimating a decrease of the BSE exposure from the birth cohort July 1995-June 1996 that matched with the decrease of the infection after June 1996. In view of the long incubation period of BSE, it is not possible to precisely assess the impact of any control measure before several years. Modeling was therefore used to estimate prospectively the efficiency of the ban of meat and bone meal extended to all farm species in November 2000. Using parameters about age at infection and incubation time estimated earlier, we assessed the minimum time to first detection if infections still occurred. We have waited up to June 2007 to know if less than 100 infections occurred among French cattle during the 6 months following January 2001.

Estimates of the prevalence of transmissible spongiform encephalopathies in sheep and goats in France in 2002.

An active surveillance programme for transmissible spongiform encephalopathies (TSES) in sheep and goats was implemented in France in 2002 at abattoirs and rendering plants. The analysis of the results of this programme highlighted three biases: a potentially non-random sampling scheme in both rendering plants and abattoirs, a heterogeneous geographical sampling ratio, and the use of two diagnostic tests of unequal sensitivity. Simulations were run to estimate the prevalence of TSES by taking these biases into account. A comparison of the prevalence of TSES calculated from the raw data with the simulation results showed that the effects of non-random sampling were minor in comparison with the effects of the heterogeneous geographical sampling ratio and the use of two diagnostic tests.

Prevalence of BSE in cattle found dead, euthanased or emergency slaughtered on farms in western France in 2000, 2001 and 2002.

The overall trend and the trend within birth cohorts of the prevalence of bovine spongiform encephalopathy (BSE) in cattle found dead, euthanased or emergency slaughtered on farms in the Bretagne, Basse Normandie and Pays de la Loire regions of France, during the periods from August 7 to December 22 in 2000, 2001 and 2002, were analysed by non-conditional logistic regression, adjusted for the region and for the type of animals. The overall prevalence of BSE during these three periods decreased from 2.71 per 1000 in 2000 to 1.41 per 1000 in 2001 and 0.42 per 1000 in 2002. The prevalence within birth cohorts started to decrease for the cohort born between July 1, 1995 and June 30, 1996 (cohort 95/96) and the trend was reinforced for cohort 96/97, suggesting that the exposure of animals to the BSE agent had started to decrease for animals born after July 1995, that is, one year before the ban on specified risk materials in meat and bone meal was implemented in France. However, considering that most of the animals would have been infected at between six and 18 months of age, the decrease may have been due, at least partly, to this control measure.

Targeted surveillance to assess the prevalence of BSE in high-risk populations in western France and the associated risk factors.

A pilot study was set up for the first time in France in August 2000, to obtain more precise estimates on the BSE epidemic in France. Three categories of cattle at risk of BSE (found dead on-farm, euthanased and emergency slaughtered) were sampled exhaustively from August 7 to December 22, 2000, in the three regions assumed to be the most affected with BSE in France (Basse-Normandie, Bretagne and Pays de la Loire). The samples were checked by using Prionics tests, and positive samples were confirmed by Western blot or immunohistochemistry. The overall prevalence of positive cattle was 0.16 per cent. Multifactorial logistic regression showed that there was a significantly higher prevalence among cattle from the birth cohorts July 1993 to June 1994 and July 1994 to June 1995, than among those born before July 1993, and among the categories 'euthanased' and 'emergency slaughtered' than among the category 'dead on-farm, and a higher prevalence in the regions Pays de la Loire and Bretagne than in Basse-Normandie. No significant differences in the prevalence of BSE were observed between dairy, beef suckler and mixed herds.

Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature.

BACKGROUND: The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC). METHODS: A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed. Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients. RESULTS: The median follow-up for the whole series was 72 months. Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3--T4 lesions), and the 5-year overall survival rate was 54.4%. Metachronous inguinal metastases were seen in 19 patients (7.8%), and the 5-year overall survival rate of these patients was 41.4%. An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors). CONCLUSIONS: The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors.

The prognostic value of etoposide area under the curve (AUC) at first chemotherapy cycle in small cell lung cancer patients: a multicenter study of the groupe Lyon-Saint-Etienne d'Oncologie Thoracique (GLOT).

PURPOSE: To assess the potential relationships between systemic exposure to doxorubicin, etoposide and ifosfamide at first chemotherapy cycle and therapeutic effect, tumor response, toxicity, and survival, in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Twenty-four patients referred to five different centers with either thorax-limited or metastatic SCLC entered the study. All but one received two induction courses of the 3 day-AVI (doxorubicin 50 mg/m(2) day 1, etoposide 120 mg/m(2) day 1, 2, 3, ifosfamide 2000 mg/m(2) day 1, 2) regimen. Individual plasma samples were collected at the first course and complete concentration data on 24 courses were available. Drugs exposures were estimated using a population pharmacokinetic method and expressed as clearance (Cl), area under the curve (AUC), and AUC-intensity (AUC/cycle duration). Responding patients received thoracic irradiation+concomitant cisplatinum-etoposide (limited disease) or four more courses of AVI (extensive disease). The impact of exposure parameters on haematological toxicity, tumor response and overall survival was assessed using linear regression, the Mann-Whitney U-test and the log-rank test/Kaplan-Meier estimation, respectively. RESULTS: Twenty-three patients could be evaluated for response and survival. We found no relationship between drug exposure and haematological toxicity but all patients had received Granulocyte-Colony Stimulating Factor support. Tumor response was marginally influenced by ifosfamide AUC. In patients with etoposide AUC>254.8 mg h/l, 1-year survival was 50.0 vs. 9.1% in the other group (median 11.4 vs. 7.1 months, P=0.02), with respect to established prognostic factors. In patients with extensive disease only (n=15), 1-year survival was 42.9 vs. 0% (median 11.3 vs. 5.3 months, P=0.01). CONCLUSION: This study strongly suggests that SCLC patients should benefit from sufficient etoposide exposure at first cycle to improve survival. Adaptative control based on plasma concentration measurements should be tested in further studies assessing various polychemotherapy regimens.

[Curative treatment of non-metastatic esophageal cancer: concomitant chemoradiotherapy and high-dose-rate endoluminal curietherapy boost]. / Traitement à visée curative du cancer de l'oesophage non métastatique: chimio-radiothérapie concomitante et surdosage par curiethérapie endoluminale à haut débit de dose.

OBJECTIVES: The aim of this study was to evaluate the feasibility, toxicity, and efficacy of a curative combination of chemo-radiotherapy with high-dose-rate brachytherapy (HDRB) in patients with non metastatic esophageal cancer. PATIENTS AND METHODS: Fifty-two patients with esophageal carcinoma were treated with > 50 Gy external irradiation, concomitant chemotherapy (5FU-CDDP) followed by HDRB delivering 12.5 Gy (6-20) as a boost. Twelve patients were stage I, 20 stage IIa, 5 stage IIb, and 13 stage III, 1 Tis, 1 stage N unknown. Surgery was not indicated for medical reasons. RESULTS: The response rate was 96%, with complete response rate 85%. The 1-, 3-, 5-year overall survival rates were 78%, 33%, and 22% respectively. A local failure occurred in 32%, and distant metastasis in 16%. Severe (grade 3, 4) acute toxicity occurred in 6 cases, severe late toxicity in 2 cases and there was 1 toxic death. Tumoral length > or = 5 cm and stage IIa, IIb and III versus stage 1 indicated poor prognosis. CONCLUSION: This regimen is feasible and well tolerated. The 5-year overall survival is 22%, but the local failure rate is still very high. These results are encouraging and will be prospectively evaluated with currently ongoing randomized trial.

[Preoperative radiotherapy of rectal cancer. The Lyons experience, 1985-1996. Prognostic study apropos of 312 patients]. / La radiothérapie pré-opératoire du cancer du rectum. Expérience lyonnaise de 1985 à 1996. Etude pronostique à propos de 312 patients.

AIM OF STUDY: Preoperative radiotherapy is used increasingly in rectal cancer in Europe. This study is a retrospective analysis of a series of 312 patients with rectal adenocarcinoma treated by preoperative radiotherapy. MATERIAL AND METHOD: From 1985 to 1996, 312 patients were included in this study. Preoperative staging was: T2: 83, T3: 192 et T4: 21. On digital rectal examination, 25 patients were classified as N1. Endorectal sonographic staging was: uT1: 3, uT2: 77, uT3: 163, uN0: 122, uN1-2: 127. After surgery, pathological staging was: pT0: 43 (14%), pT1 24, pT2: 81, pT3: 151, pN0: 229, pN1-2: 81. Radiotherapy was delivered to the posterior pelvis with an accelerated schedule 39 Gy/13 fractions/17 days with x 18 MV. RESULTS: Median follow-up is 54 months. For pM0 patients (297 patients), the overall 5-year survival rate is 67%. Local failure rate is 9%. Since 1986, the rate of sphincter saving surgery is close to 65%. Various parameters related to the tumor were found to be significant prognostic factors on multivariate analysis in relation to 5-year overall survival rate: the T stage as judged by digital rectal examination and endorectal sonography, the N stage as evaluated on digital rectal examination but not with endorectal sonography. Pathological examination of the operative specimen retains a very strong prognostic value for pT and pN. CONCLUSION: Pathological examination of the specimen of rectal carcinoma retains a very strong prognostic value after preoperative radiation therapy. Endorectal sonography is of interest to evaluate T staging of the tumor but is not reliable for N stage.

[Radiotherapy of cancer of the anal canal. 15 years experience at the Lyon civil hospices and brief review of the literature]. / La radiothérapie du cancer du canal anal. Quinze ans d'expérience aux Hospices Civils de Lyon et brève revue de la littérature.

AIM: Retrospective analysis of a series of 287 anal canal carcinomas seen during a 15-year period in the Department of Radiotherapy Oncology of Hospices Civils de Lyon. MATERIAL AND METHOD: Between 1980 and 1995, 287 patients were managed in the radiotherapy department of Hospices Civils de Lyon. In 25 cases, the patients were referred for recurrence. Post or preoperative irradiation was performed in 12 and 23 cases. Palliative treatment was given to 15 cases and simple follow-up in 7 cases. Radiotherapy was given to 205 patients. In 71 cases irradiation alone and in 134 concomitant radiochemotherapy was given. RESULTS: The 5-year overall survival of the group treated by radiotherapy (205 patients) was 71.5% and the 10 year-overall survival was 60.8%. The specific survival at 5 and 10 years was 81.9% and 74.7% respectively. At 5 years the overall survival was 78% for the group treated by concomitant radiochemotherapy and 60% for the group treated by irradiation alone. CONCLUSION: Radiotherapy is the standard treatment for anal canal carcinoma. Radiochemotherapy seems to improve results in advanced cases. The best irradiation of technique has yet to be defined.