Extended-spectrum cephalosporin resistance in Escherichia coli in cows and calves after dry cow therapy with cephapirin or cloxacillin.

The use of intramammary antimicrobials at drying-off is a common preventive measure against mastitis in dairy cows, but its potential to select gut bacteria for developing antimicrobial resistance remains debated. This controlled field study investigated whether dry cow therapy with the first-generation cephalosporin, cephapirin, results in greater selection of extended-spectrum cephalosporin-resistant (ESC-R) and extended-spectrum beta lactamase (ESBL) producing Escherichia coli in dairy cows and their neonatal calves than treatment with the narrow-spectrum penicillin cloxacillin. On three dairy farms with high antibiotic use and an ESBL history, twenty-two dairy cows carrying ESC-R E. coli before drying off were systematically allocated to receive cephapirin or cloxacillin using alternating assignment within farms according to expected dry-off date. Fecal and colostrum samples from cows and their offspring were collected longitudinally for quantitative and genomic analysis. Cephapirin residues in colostrum were consistently below the maximum residue limit. In this field trial, we found no evidence that dry cow therapy with the first-generation cephalosporin cephapirin resulted in greater selection or transmission of ESC-R E. coli than dry cow therapy with the narrow-spectrum penicillin cloxacillin in dairy cows and their offspring when using a 1.0 log10 non-inferiority margin. Using the tight primary 0.5 log₁₀ margin, non-inferiority was not demonstrated in cows after dry cow therapy, whereas the overall calf estimate met this criterion of non-inferiority. Wide confidence intervals, particularly in cows, reflect the limited sample size and imprecision of the estimates and preclude definitive conclusions. Intestinal colonization with ESC-R E. coli in dairy cows was transient throughout the dry period, whereas neonatal calves rapidly became colonized after birth and exhibited a high prevalence and level of carriage. The observed diversity of resistance genes and sequence types, together with evidence for horizontal rather than vertical transmission, indicates that the calf environment may represent an important reservoir of resistant E. coli. Further research is needed to identify the sources of environmental transmission and to better understand factors influencing early-life colonization, thereby informing mitigation strategies to reduce the emergence and dissemination of ESBL/AmpC-producing E. coli on dairy farms.