Effect of Danofloxacin Treatment on the Development of Fluoroquinolone Resistance in Campylobacter jejuni in Calves

Abstract

Campylobacter is a leading cause of foodborne gastroenteritis. Recent studies have indicated a rise in fluoroquinolone-resistant (FQ-R) Campylobacter in cattle, where FQ is used to control bovine respiratory disease (BRD). To assess the effect of danofloxacin treatment on the development of FQ-resistance in C. jejuni, 30 commercial calves were divided into Group 1, Group 2, and Group 3 (n = 10), and were all inoculated orally with FQ-susceptible (FQ-S) C. jejuni; seven days later, Group 3 was challenged with transtracheal Mannheimia haemolytica, and one week later, Group 2 and Group 3 were injected subcutaneously with danofloxacin. Rectal feces were collected to determine relative percentages of FQ-R Campylobacter via culture. Before oral inoculation with C. jejuni, 87% of calves were naturally colonized by FQ-R C. jejuni. Two days after the inoculation, FQ-R C. jejuni decreased substantially in the majority of calves. Within 24 h of danofloxacin injection, almost all C. jejuni populations shifted to an FQ-R phenotype in both FQ-treated groups, which was only transitory, as FQ-S strains became predominant during later periods. Genotyping indicated that the spike seen in FQ-R C. jejuni populations following the injection was due mainly to enrichment of preexisting FQ-R C. jejuni, rather than development of de novo FQ resistance in susceptible strains. These results provide important insights into the dynamic changes of FQ-resistant Campylobacter in cattle in response to FQ treatment.

Influence of Single Dose Enrofloxacin Injection on Development of Fluoroquinolone Resistance in Campylobacter jejuni in Calves

“…This finding indicated that a single dose subcutaneous enrofloxacin treatment, as employed in the current study, did not result in any detectable level of FQ-resistance development from FQ-susceptible C. jejuni inhabiting the intestine of calves. As mentioned above, highly similar results were obtained with another FQ-antibiotic (danofloxacin) treatment of calves in a recent experimental study conducted by our research group [ 38 ], as well as in a field study in which feedlot cattle were treated with a single subcutaneous dose (7.5 mg/kg) of enrofloxacin for metaphylactic purposes [ 44 ].…”

“…Therefore, it is crucial to assess if the FQ treatment regimen can be optimized to minimize the selection pressure on Campylobacter and the magnitude of FQ-resistance in cattle. As shown in our recent study [ 38 ], single dose subcutaneous danofloxacin (an FQ antibiotic) treatment did not cause any quantifiable level of de novo resistance in FQ-susceptible C. jejuni strains in the intestine of either healthy or BRD-induced calves. In that study, the vast majority of calves were naturally colonized (an un-ideal situation for experimental purposes) by FQ-resistant C. jejuni prior to the experimental inoculation, which experienced a sharp but brief spike after the FQ injection.…”

“…In that study, the vast majority of calves were naturally colonized (an un-ideal situation for experimental purposes) by FQ-resistant C. jejuni prior to the experimental inoculation, which experienced a sharp but brief spike after the FQ injection. In contrast, the calves used in the current study were mostly free of natural Campylobacter colonization at the procurement, which was highly desirable to perform the principal goal of this investigation since finding (FQ-resistant) Campylobacter -free calves from commercial sources can be quite a difficult task [ 38 ]. A key finding of the present study is that single dose subcutaneous enrofloxacin treatment (regardless of the dose administered) did not result in the emergence of FQ resistance in FQ-susceptible C. jejuni colonizing the intestine of calves (irrespective of the BRD status).…”

“…The magnitude of colonization by Campylobacter in the chicken intestinal tract is typically very robust, reaching up to 9.0 log 10 CFU/g in the ceca [ 50 ]. However, the colonization level by Campylobacter in the cattle intestine is usually much lower than in chickens (i.e., 2 to 5 log10 CFU/g feces) [ 38 , 51 ]. Similarly, in the current study, the mean colonization level (as measured in freshly collected rectal feces) of C. jejuni ranged between 4.1 and 4.6 log10 CFU/g feces although this value was close to 7 log10 CFU/g prior to the enrofloxacin injection in a few individual calves (partly shown in Figure 1 ).…”

“…In an attempt to begin to better understand the driving factors responsible for the ongoing rise seen in FQ-resistance in bovine Campylobacter , we recently carried out a series of experiments to determine the effect of different FQ antibiotic treatment regimens on resistance development in both healthy and BRD-induced cattle. In the first study [ 38 ], we showed that a single dose of danofloxacin treatment had a minimal or no role in the emergence of de novo FQ-resistance in calves experimentally inoculated with FQ-susceptible C. jejuni strains. The current study is an expansion of the previous work and conducted to determine the effect of two different single doses of another commonly used FQ antibiotic (i.e., enrofloxacin) for BRD control on resistance development in C. jejuni in cattle.…”