Effects of Intravenous Antimicrobial Drugs on the Equine Fecal Microbiome.

Alterations in the gastrointestinal microbiota after antimicrobial therapy in horses can result in loss of colonization resistance and changes in bacterial metabolic function. It is hypothesized that these changes facilitate gastrointestinal inflammation, pathogen expansion and the development of diarrhea. The objectives of this study were to determine the effect of intravenous administration of antimicrobial drugs (ceftiofur, enrofloxacin, oxytetracycline) on equine fecal bacterial communities over time, to investigate whether those changes are detectable after 5 days of treatment and whether they persist over time (30 days). Sixteen horses were randomly assigned into 4 treatment groups: group 1 (enrofloxacin, n = 4); group 2 (ceftiofur sodium, n = 4); group 3 (oxytetracycline, n = 4); group 4 (0.9% saline solution, placebo, n = 4). Antimicrobial therapy was administered for 5 days. Fecal samples were obtained before (day 0) and at 3, 5 and 30 days of the study period. Bacterial DNA was amplified using specific primers to the hypervariable region V1−V3 of the 16S rRNA gene using a 454 FLX-Titanium pyrosequencer. Antimicrobial therapy failed to cause any changes in physical examination parameters, behavior, appetite or fecal output or consistency throughout the study in any horse. There was a significant effect of treatment on alpha diversity indices (richness) over the treatment interval for ceftiofur on days 0 vs. 3 (p < 0.05), but not for other antimicrobials (p > 0.05). Microbial composition was significantly different (p < 0.05) across treatment group and day, but not for interactions between treatment and day, regardless of taxonomic level and beta-diversity distance metric. The most significant antimicrobial effects on relative abundance were noted after intravenous administration of ceftiofur and enrofloxacin. The relative abundance of Fibrobacteres was markedly lower on day 3 compared to other days in the ceftiofur and enrofloxacin treatment groups. There was an increase in Clostridia and Lachnospiraceae from day 0 to days 3 and 5 in ceftiofur and enrofloxacin treated groups. These findings showed the negative effect of antimicrobial drugs on bacterial communities associated with gut health (Fibrobacteres and Lachnospiraceae) and indicate that changes in specific taxa could predispose horses to gastrointestinal inflammation and the development of diarrhea.

Pathobiology and management of laboratory rodents administered CDC category A agents.

The Centers for Disease Control and Prevention Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. These agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. Frequently rodent models are used to study the pathobiology of these agents. Although much is known regarding naturally occurring infections in humans, less is documented on the sources of exposures and potential risks of infection to researchers and animal care personnel after the administration of these hazardous substances to laboratory animals. Failure to appropriately manage the animals can result both in the creation of workplace hazards if human exposures occur and in disruption of the research if unintended animal exposures occur. Here we review representative Category A agents, with a focus on comparing the biologic effects in naturally infected humans and rodent models and on considerations specific to the management of infected rodent subjects. The information reviewed for each agent has been curated manually and stored in a unique Internet-based database system called HazARD (Hazards in Animal Research Database, http://helab.bioinformatics.med.umich.edu/hazard/) that is designed to assist researchers, administrators, safety officials, Institutional Biosafety Committees, and veterinary personnel seeking information on the management of risks associated with animal studies involving hazardous substances.