Outbreak of Multidrug-Resistant Salmonella Heidelberg Infections Linked to Dairy Calf Exposure, United States, 2015-2018.

In August 2016, the Wisconsin Department of Health Services notified the U.S. Centers for Disease Control and Prevention of multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg infections in people who reported contact with dairy calves. Federal and state partners investigated this to identify the source and scope of the outbreak and to prevent further illnesses. Cases were defined as human Salmonella Heidelberg infection caused by a strain that had one of seven pulsed-field gel electrophoresis (PFGE) patterns or was related by whole genome sequencing (WGS), with illness onset from January 1, 2015, through July 2, 2018. Patient exposure and calf purchase information was collected and analyzed; calves were traced back from the point of purchase. Isolates obtained from animal and environmental samples collected on-farm were supplied by veterinary diagnostic laboratories and compared with patient isolates using PFGE and WGS. Antimicrobial susceptibility testing by standardized broth microdilution was performed. Sixty-eight patients from 17 states were identified. Forty (63%) of 64 patients noted cattle contact before illness. Thirteen (33%) of 40 patients with exposure to calves reported that calves were sick or had died. Seven individuals purchased calves from a single Wisconsin livestock market. One hundred forty cattle from 14 states were infected with the outbreak strain. WGS indicated that human, cattle, and environmental isolates from the livestock market were genetically closely related. Most isolates (88%) had resistance or reduced susceptibility to antibiotics of ≥5 antibiotic classes. This resistance profile included first-line antibiotic treatments for patients with severe salmonellosis, including ampicillin, ceftriaxone, and ciprofloxacin. In this outbreak, MDR Salmonella Heidelberg likely spread from sick calves to humans, emphasizing the importance of illness surveillance in animal populations to prevent future spillover of this zoonotic disease.

Modeling the Effect of Tylosin Phosphate on Macrolide-Resistant Enterococci in Feedlots and Reducing Resistance Transmission.

Tylosin phosphate (TYL) is administered to more than 50% of U.S. beef cattle to reduce the incidence of liver abscesses but may increase the risk of macrolide-lincosamide-streptogramin-resistant bacteria disseminating from the feedlot. Limited evidence has been collected to understand how TYL affects the proportion of resistant bacteria in cattle or the feedlot environment. We created a mathematical model to investigate the effects of TYL administration on Enterococcus dynamics and examined preharvest strategies to mitigate the impact of TYL administration on resistance. The model simulated the physiological pharmacokinetics of orally administered TYL and estimated the pharmacodynamic effects of TYL on populations of resistant and susceptible Enterococcus within the cattle large intestine, feedlot pen, water trough, and feed bunk. The model parameters' population distributions were based on the available literature; 1000 Monte Carlo simulations were performed to estimate the likely distribution of outcomes. At the end of the simulated treatment period, the median estimated proportion of macrolide-resistant enterococci was only 1 percentage point higher within treated cattle compared with cattle not fed TYL, in part because the TYL concentrations in the large intestine were substantially lower than the enterococci minimum inhibitory concentrations. However, 25% of the simulated cattle had a >10 percentage point increase in the proportion of resistant enterococci associated with TYL administration, termed the TYL effect. The model predicts withdrawing TYL treatment and moving cattle to an antimicrobial-free terminal pen with a low prevalence of resistant environmental enterococci for as few as 6 days could reduce the TYL effect by up to 14 percentage points. Additional investigation of the importance of this subset of cattle to the overall risk of resistance transmission from feedlots will aid in the interpretation and implementation of resistance mitigation strategies.