Table 14.
Alali et al. (2004) | Berge et al. (2006) | Thames et al. (2012) | Pereira et al. (2014) | |
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Study design | Experimental study feeding milk spiked with antimicrobials | Experimental study feeding milk spiked with antimicrobials | Experimental study feeding milk spiked inoculated with antimicrobials | Experimental study feeding milk spiked with antimicrobials |
Country | US | US | US | US |
Farm | Two rooms in a Biosafety Level 2 facility | Calf ranch for heifer replacement, veal and dairy beef | Experimental study feeding milk spiked with antimicrobials | Experimental farm |
Treatment | 1 group fed spiked milk with oxytetracycline and neomycin/1 group control with no drug residue/both groups challenged with a nalidixic acid resistant E. coli O157:H7 strain after 1–2 weeks | 1 group fed spiked milk/one group residue free milk replacer | 1 group fed subtherapeutic concentrations of drug residues spiked in milk/1 group fed therapeutic concentrations in spiked milk/1 group fed residue free milk replacer | 1 group fed spiked milk with drug residues (DR)/1 group control with no drug residue (NR) |
Feeding scheme | Spiked milk fed from week 1 till 8 weeks after inoculation | Spiked milk fed from week 1 until week 4 | Subtherapeutic group was fed spiked milk from day 1 until weaning; therapeutic group was fed spiked milk from day 37 for 14 days | Spiked milk fed from week 1 till week 6; 7.6 L per day |
Antimicrobials/concentration | Oxytetracycline (200 mg/kg or 2 mg/kg body weight daily) and neomycin (400 mg/kg or 4 mg/kg body weight daily) | Tetracycline hydrochloride and neomycin sulfate at concentrations of 22 mg/kg body weight/day, each | Subtherapeutic group: neomycin sulfate and oxytetracyline hydrochloride at concentrations of 10 mg/calf per day, each. Therapeutic group: same Antimicrobials at concentrations each of 1,000 mg/calf per day | Ceftiofur, penicillin, ampicillin, oxytetracycline at concentrations of 0.1, 0.05, 0.01, 0.3 μg/mL, respectively |
Amount calves | 18 male calves (9 treated; 9 control) | 30 treated calves/60 control calves | 28 divided over three groups (treated/therapeutic/control) (amount of calves/group is not provided) | 30 male calves (15 treated; 15 control) in three individual studies of each 10 calves (5 treated/5 control) |
Method and criteria applied to interpret resultsa | Nalidixic acid resistant E. coli O157:H7 from faecal rectal material isolated on MacConkey agar with 20 μg/mL nalidixic acid and detection after enrichment | E. coli from faecal swabs isolated on MacConkey agar; 909 isolates; antimicrobial resistance by disk diffusion according to NCCLS (2002) | Quantitative PCR resistance genes detected in faecal samples | E. coli from faecal samples isolated on MacConkey agar; 270 isolates; antimicrobial resistance tested by disk diffusion according to CLSI (2008) |
Antimicrobial resistance | Amount of E. coli O157:H7 shed was compared between treated and non‐treated group | Resistance to 12 antimicrobials tested | Detection by PCR of the following resistance genes tet(C), tet(G), tet(W),tet(X) (tetracycline resistance), ermB, ermF (MLSs resistance), and sul1, sul2 (sulfonamides resistance) | Resistance to 12 antimicrobials |
Time animals tested for faecal shedding | Weekly, started from 2 days after inoculation to 8 weeks after inoculation | Day 1, day 14, day 28 | Daily for 7 days starting at week 6 and weekly after weaning till week 12 | Weekly from week 1 till week 6 |
Result |
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Main relevant results as reported in abstract | ‘The percentage of calves shedding nalidixic acid‐resistant E. coli O157:H7 in the feces in the antimicrobial‐fed group was higher (p < 0.001) early in the study period (d 6 and 10) compared with the control group fed no antimicrobials. There was no difference between treatment and control groups in the concentration of E. coli O157 in feces that were positive at quantifiable concentrations. A comparison of the duration of faecal shedding between treated and untreated calves showed no significant difference between groups. Supplementation of milk replacer with antimicrobials may increase the probability of E. coli O157:H7 shedding in dairy calves, but the effect appeared to be of low magnitude and short duration’ | In‐feed antimicrobials were associated with higher levels of multiple AMR in faecal E. coli. In calves not receiving in‐feed antimicrobials, older calves had higher levels of resistance compared to day‐old calves' | ‘Relative abundance (gene copies normalized to 16S rRNA genes) of tet(O) was higher in claves fed the highest dose of antimicrobial (therapeutic group) than in the other treatments. All genes, except tet(C) and intI1 were detectable in faeces from 6 weeks onward, and tet(W) and tet(G) significantly increased even in control calves' | ‘A significantly greater proportion of E. coli resistant to ampicillin, cefoxitin, ceftiofur, streptomycin and tetracycline was observed in DR calves when compared to NR calves. Additionally, isolates from DR calves had a significant decrease in susceptibility to ceftriaxone and ceftiofur when compared to isolates from NR calves. A greater proportion of E. coli isolates from calves in the DR group were resistant to 3 or more antimicrobial drugs when compared to calves in the ND group. These findings highlight the role that low concentrations of antimicrobial drugs have on the evolution and selection of resistance to multiple antimicrobial drugs in vivo’ |
Main uncertainties and limitations of the study |
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Because the body weight of the calves is not provided, it is not possible to quantify the actual doses of antimicrobials received by the calves fed with spiked milk. So no quantitative comparison with other studies is possible on the relationship between antimicrobial residue concentration and AMR induction |
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Limitations concerning the representativeness of the results because the animals were housed in an experimental farm and only a limited amount of animals were included in the study |
See Appendix E.