Exposure to antimicrobials through the milk diet or systemic therapy is associated with a transient increase in antimicrobial resistance in fecal Escherichia coli of dairy calves

Abstract

The objective of this prospective cohort study was to describe the relationship between exposure to antimicrobials, through both the milk diet and systemic therapy, and to describe antimicrobial resistance of fecal Escherichia coli in dairy calves pre- and postweaning. A convenience sample of 15 Minnesota dairy farms was chosen, representing 3 equal cohorts of milk diet fed to preweaned calves: medicated milk replacer (MMR), nonmedicated milk replacer (NMR), or pasteurized nonsaleable milk (PNM). Five newborn calves were enrolled on each farm, with fecal samples collected from each calf at 1, 3, 5, and 16 wk of age. After isolation, 3 colonies of E. coli were randomly selected from each sample to determine antimicrobial susceptibility by minimum inhibitory concentration (Sensititer, Thermo Scientific, Waltham, MA) to 8 antimicrobials in 8 classes. The isolate was given an antimicrobial resistance score (ARS) according to the number of antimicrobial classes to which it was resistant. Any isolate resistant to 3 or more antimicrobials was defined as being multidrug resistant (MDR). Relationships between ARS and MDR (dependent variables) and possible explanatory variables were analyzed using mixed multivariable linear and logistic regression models, respectively, with critical P-values adjusted for multiple contrasts. Seventy percent of isolates were resistant to sulfadimethoxine. For wk 1 and 3, the mean ARS values were greatest for fecal E. coli from calves fed MMR or PNM compared with NMR, with no difference in ARS values between the MMR and PNM groups at either time point. At wk 5, the mean ARS value was greatest for fecal E. coli from calves fed MMR (3.56 ± 0.45; mean ± SE), intermediate for calves fed PNM (2.64 ± 0.45), and lowest for calves fed NMR (1.54 ± 0.45). However, by wk 16, the mean ARS values were ≤1.0 and did not differ among milk diets. Evaluation of the proportion of isolates with MDR mirrored the results of the ARS analysis (MDR more prevalent in MMR and PNM groups preweaning; no difference among milk diets at 16 wk). There was a tendency for an increase in ARS at wk 5 (1.28 ± 0.70), and the odds for MDR in fecal E. coli were estimated to be 5.2 (95% confidence interval = 0.67, 35.7) and 101.1 (95% confidence interval = 1.15, >999.9) higher at wk 3 and 5 if the calf was treated with a systemic antimicrobial within the 14-d period before sampling. These findings suggest that exposure to antimicrobials through the milk diet or systemic therapy may result in a transient increase in resistance in fecal E. coli, but once the antimicrobial pressure is removed, susceptible E. coli are able to flourish again, resulting in an overall decrease in resistance.

Estimating the Rates of Acquisition and loss of Resistance of Enterobacteriaceae to Antimicrobial Drugs in Pre-Weaned Dairy Calves

“…Berge et al [17] demonstrated that fecal pathogens shed by pre-weaned calves show an increase in AMR when the animals are exposed to prophylactic treatments with AMD, particularly ones added to milk replacer. A study conducted in Minnesota [26] showed similar results of transient resistance as this study does. Foutz et al [26] evaluated the AMR score (given to the isolate according to the number of antimicrobial classes to which it was resistant) between calves and observed that calves fed with medicated milk replacer had a higher AMR score than the calves fed unmedicated milk replacer.…”

“…A study conducted in Minnesota [26] showed similar results of transient resistance as this study does. Foutz et al [26] evaluated the AMR score (given to the isolate according to the number of antimicrobial classes to which it was resistant) between calves and observed that calves fed with medicated milk replacer had a higher AMR score than the calves fed unmedicated milk replacer. The resistance was transient resolving after weaning (at week 16), suggesting that once the antimicrobial pressure was removed there was a re-establishment of the susceptible E. coli bacteria [26].…”

The effect of intramammary pirlimycin hydrochloride on the fecal microbiome of early-lactation heifers

“…Other authors have determined the effect of systemic antimicrobials on the fecal microbiome and antimicrobial resistance among fecal microbiota of dairy cattle (Tragesser et al, 2006;Chambers et al, 2015), dairy calves (Foutz et al, 2018), and beef cattle (Ferguson et al, 2018;Holman et al, 2019). Similar to what was found herein with intramammary pirlimycin administration, some of these studies also found that the changes in fecal microbiota were temporary (Ferguson et al, 2018;Foutz et al, 2018).…”

“…Other authors have determined the effect of systemic antimicrobials on the fecal microbiome and antimicrobial resistance among fecal microbiota of dairy cattle (Tragesser et al, 2006;Chambers et al, 2015), dairy calves (Foutz et al, 2018), and beef cattle (Ferguson et al, 2018;Holman et al, 2019). Similar to what was found herein with intramammary pirlimycin administration, some of these studies also found that the changes in fecal microbiota were temporary (Ferguson et al, 2018;Foutz et al, 2018). More specifically, when evaluating the fecal microbiome of dairy cows treated with subcutaneously administered ceftiofur crystalline free acid sterile suspension compared with untreated controls, treated cows tended to have an increased abundance of Bacteroidia and a decrease in class Actinobacteria compared with control cows 3 d posttreatment (Chambers et al, 2015).…”

Biosensors for On-Farm Diagnosis of Mastitis

“…Therefore, the consequences of antimicrobial resistance in dairy pathogens potentially impacting human health are residual as long as safety measurements are applied and milk pasteurized (Oliver et al, 2010). However, several studies, demonstrated an increased prevalence of resistant bacteria in commensal populations from dairy animals undergoing antibiotic treatment (Foutz et al, 2018; Springer et al, 2018). Additionally, a common practice is to use non-salable milk from cows treated with antibiotics to feed young calves which carries the risk of increasing fecal shedding of AMR bacteria.…”