Antimicrobial susceptibility in E. coli and Pasteurellaceae at the beginning and at the end of the fattening process in veal calves: Comparing 'outdoor veal calf' and conventional operations.

Animal husbandry requires practical measures to limit antimicrobial resistance (AMR). Therefore, a novel management and housing concept for veal calf fattening was implemented on 19 intervention farms (IF) and evaluated regarding its effects on AMR in Escherichia (E.) coli, Pasteurella (P.) multocida and Mannheimia (M.) haemolytica in comparison with 19 conventional control farms (CF). Treatment intensity (-80%) and mortality (-50%) were significantly lower in IF than in CF, however, production parameters did not differ significantly between groups. Rectal and nasopharyngeal swabs were taken at the beginning and the end of the fattening period. Susceptibility testing by determination of the minimum inhibitory concentration was performed on 5420 isolates. The presence of AMR was described as prevalence of resistant isolates (%), by calculating the Antimicrobial Resistance Index (ARI: number of resistance of one isolate to single drugs/total number of drugs tested), by the occurrence of pansusceptible isolates (susceptible to all tested drugs, ARI=0), and by calculating the prevalence of multidrug (≥3) resistant isolates (MDR). Before slaughter, odds for carrying pansusceptible E. coli were higher in IF than in CF (+65%, p=0.022), whereas ARI was lower (-16%, p=0.003), and MDR isolates were less prevalent (-65%, p=0.001). For P. multocida, odds for carrying pansusceptible isolates were higher in IF before slaughter compared to CF (+990%, p=0.009). No differences between IF and CF were seen regarding the prevalence of pansuceptible M. haemolytica. These findings indicate that easy-to-implement measures to improve calf management can lead to a limitation of AMR in Swiss veal fattening farms.

Effects of the novel concept 'outdoor veal calf' on antimicrobial use, mortality and weight gain in Switzerland.

The aim of the intervention study 'outdoor veal calf' was to evaluate a novel concept for calf fattening which aimed at reducing antimicrobial use without compromising animal health. Management practices such as commingling of calves from multiple birth farms, crowding, and suboptimal barn climate are responsible for high antimicrobial use and mortality in the veal calf population. The risk of selecting bacteria resistant to antimicrobials and of economic losses is accordingly elevated. The 'outdoor veal calf' concept, implemented in nineteen intervention farms (IF), is based on three main measures: 1. purchased calves are transported directly from neighboring birth farms to the fattening facility instead of commingling calves in livestock dealer trucks; 2. each calf is vaccinated against pneumonia after arrival and completes a three-week quarantine in an individual hutch; and 3. the calves spend the rest of the fattening period in outdoor hutches in groups not exceeding 10 calves. The covered and bedded paddock and the group hutches provide shelter from cold weather and direct sunshine, constant access to fresh air is warranted. Nineteen conventional calf fattening operations of similar size served as controls (CF). Every farm was visited once a month for a one-year period, and data regarding animal health, treatments, and production parameters were collected. Treatment intensity was assessed by use of the defined daily dose method (TIDDD in days per animal year), and calf mortality and daily weight gain were recorded in both farm groups. Mean TIDDD was 5.3-fold lower in IF compared to CF (5.9 ±â€¯6.5 vs. 31.5 ±â€¯27.4 days per animal year; p < 0.001). Mortality was 2.1-fold lower in IF than in CF (3.1% ± 2.3 vs. 6.3 % ± 4.9; p = 0.020). Average daily gain did not differ between groups (1.29 ±â€¯0.17 kg/day in IF vs. 1.35 ±â€¯0.16 kg/day in CF; p = 0.244). A drastic reduction in antimicrobial use and mortality was achieved in the novel 'outdoor veal calf' system without compromising animal health. The principles of risk reduction used in designing the system can be used to improve management and animal health, decrease the need for antimicrobial treatments and thus selection pressure on bacteria in veal operations.

Antibiotic and quaternary ammonium compound resistance in Escherichia coli from calves at the beginning of the -fattening period in Switzerland (2017).

INTRODUCTION: In the Swiss veal calf production, antimicrobials and disinfectants are used to control bacterial infectious diseases, leading to a risk of selecting for a resistant bacterial population. While the prevalence of antibiotic resistance in E. coli from calves has been monitored at slaughterhouses in Switzerland since 2006, the resistance situation of E. coli from young calves entering the fattening period is not known. A total of 100 calves entering the fattening period in 20 geographically distant farms in Switzerland were screened for the presence of E. coli using rectal swabs in 2017. Genetic diversity between isolates was determined using repetitive palindromic Polymerase Chain Reaction (rep-PCR) revealing a genetically diverse E. coli population. Susceptibility to 13 antibiotics and to alkyldimethylbenzylammonium (ADBAC) was determined by the measurement of the minimal inhibitory concentration. Antibiotic and quaternary ammonium compound (QAC) resistance genes were identified using microarray and Polymerase Chain Reaction (PCR). Sixty-four percent of the isolates were resistant to at least one antibiotic, and 52% also exhibited decreased susceptibility to ADBAC. Resistance to more than 3 antibiotics was found in 40% of the isolates. Isolates exhibited resistance to tetracycline (57%) associated with the presence of tet genes (tet(A), (B), (E), (G)), to sulfonamides (61%) (sul1, sul2, sul3), ampicillin (56%) (blaTEM-1), trimethoprim (32%) (dfrA), phenicols (31%) (catA1, cmlA1, floR), gentamicin (27%) (ant(2")-Ia, aac(3)-IVa, aac(3)-VIa), and cefotaxime (2%) (blaCTX-M-14 (ESBL)). Mutations in GyrA (S83L) and ParC (S80I) were found in the fluoroquinolone-resistant isolates (6%). All isolates were susceptible to colistin, tigecycline and meropenem. No association between the presence of decreased susceptibility to ADBAC and qac genes was observed. In conclusion, antibiotic and QAC resistant E. coli are present in the gastrointestinal tract of young calves at the beginning of the fattening period, emphasizing the need for appropriate and reduced use of antibiotics and QAC-containing disinfectants in order to limit further selection of these bacteria during the fattening period.

INTRODUCTION: Dans la production de veaux en Suisses, des antimicrobiens et des désinfectants sont utilisés pour contrôler les maladies infectieuses bactériennes, ce qui entraîne un risque de sélection d'une population bactérienne résistante. Si la prévalence de la résistance de E. coli aux antibiotiques chez les veaux est surveillée dans les abattoirs suisses depuis 2006, la situation de la résistance de E. coli chez les jeunes veaux au début de la période d'engraissement n'est pas connue. Un total de 100 veaux entrant dans la période d'engraissement dans 20 exploitations géographiquement éloignées de Suisse ont été testés en 2017 pour détecter la présence de E. Coli à l'aide de prélèvements rectaux. La diversité génétique entre les isolats a été déterminée à l'aide de la réaction de polymérase en chaîne répétitive palindrome (rep-PCR) révélant une population de E.coli génétiquement diversifié. La sensibilité à 13 antibiotiques et au chlorure d'alkyldiméthylbenzylammonium (ADBAC) a été déterminée par la mesure de la concentration inhibitrice minimale. Les gènes de résistance aux antibiotiques et aux composés d'ammonium quaternaire (QAC) ont été identifiés à l'aide d'une puce à ADN et de la réaction de polymérase en chaîne (PCR). Soixante-quatre pour cent des isolats étaient résistants à au moins un antibiotique et 52% présentaient également une diminution de la sensibilité à l'ADBAC. Une résistance à plus de 3 antibiotiques a été trouvée dans 40% des isolats. Les isolats présentaient une résistance à la tétracycline (57%) associée à la présence de gènes tet (tet (A), (B), (E), (G)), aux sulfonamides (61%) (sul1, sul2, sul3), à l'ampicilline (56%) (blaTEM-1), au triméthoprime (32%) (dfrA), aux phénicols (31%) (catA1, cmlA1, floR), à la gentamicine (27%) (ant(2'')-Ia, aac (3) -IVa, aac (3) -VIa) et à la céfotaxime (2%) (blaCTX-M-14 (BLSE)). Les isolats résistants aux fluoroquinolones (6%) présentaient des mutations dans GyrA (S83L) et ParC (S80I). Tous les isolats étaient sensibles à la colistine, à la tigécycline et au méropénème. Aucune association entre la présence d'une sensibilité diminuée à l'ADBAC et les gènes qac n'a été observée. En conclusion, des E. coli résistants aux antibiotiques et aux QAC sont présents dans le tractus gastro-intestinal des jeunes veaux au début de la période d'engraissement, ce qui souligne la nécessité d'un usage approprié et réduit d'antibiotiques et de désinfectants contenant un QAC afin de limiter la sélection ultérieure de ces bactéries au cours de la période d'engraissement.

Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases.

An acidic domain (AD) of gp130 was previously found to interact with the Src family kinase (SFK) Hck. Here, the influence of myristoylated peptides derived from this AD was assessed in the mouse myeloma cell line, 7TD1. The IL-6-dependent growth of 7TD1 cells was reduced by approximately 75%, if 100 microM of myristoylated 18mer peptide (18AD) was included in the growth medium, but was unaffected by a control peptide with scrambled sequence (18sc). A similar differential inhibition by peptides 18AD and 18sc was observed for the erythropoietin-dependent growth of BaF-EH cells expressing chimeric erythropoietin receptor-gp130 and human Hck and for the human myeloma cell line INA-6. While the peptide 18AD concentration inhibiting 50% was approximately 30 microM in 7TD1 and BaF-EH cells, peptide 18AD did not significantly inhibit growth of IL-6-independent MM1.S myeloma and OKT1 hybridoma cells or of BaF-EH cells supplied with IL-3. Treatment with 100 microM peptide 18AD caused the same degree or 60% of apoptosis induction as IL-6 deprivation in 7TD1 or INA-6 cells, respectively. Co-immunoprecipitation experiments revealed that peptide 18AD interfered with the association of Hck and gp130 in 7TD1 lysates in a concentration-dependent manner. IL-6-treatment of INA-6 cells induced the kinase activities of Fyn, Lyn and Hck, but not Src, and the IL-6-induced SFK activities were inhibited by peptide 18AD. Expression in 7TD1 cells of a kinase-inactive Hck mutant (K269R) elicited a dominant-negative effect on cell number increases providing further evidence that SFKs are required for gp130 signalling in myeloma cells.