Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers.

Fluoroquinolones are a class of antimicrobial commonly used in human medicine, and deemed critical by the World Health Organization. Nonetheless, two formulations are approved for the treatment of respiratory disease in beef cattle. The objective of this study was to determine the gastrointestinal pharmacokinetics and impact on enteric bacteria of cattle when receiving one of the two dosing regimens (high: 40 mg/kg SC once or low: 20 mg/kg IM q48hr) of danofloxacin, a commonly utilized synthetic fluoroquinolone in veterinary medicine. Danofloxacin was administered to 12 steers (age 7 months) fitted with intestinal ultrafiltration devices at two different dosing regimens to assess the gastrointestinal pharmacokinetics, the shifts in the gastrointestinal microbiome and the development of resistant bacterial isolates. Our results demonstrated high intestinal penetration of danofloxacin for both dosing groups, as well as, significant differences in MIC values for E. coli and Enterococcus between dosing groups at selected time points over a 38 day period. Danofloxacin treatment consistently resulted in the Euryarchaeota phyla decreasing over time, specifically due to a decrease in Methanobrevibacter. Although microbiome differences were minor between dosing groups, the low dose group had a higher number of isolates with MIC values high enough to cause clinically relevant resistance. This information would help guide veterinarians as to appropriate dosing schemes to minimize the spread of antimicrobial resistance.

Clostridioides difficile carriage in animals and the associated changes in the host fecal microbiota.

The relationship between the gut microbiota and Clostridioides difficile, and its role in the severity of C. difficile infection in humans is an area of active research. Intestinal carriage of toxigenic and non-toxigenic C. difficile strains, with and without clinical signs, is reported in animals, however few studies have looked at the risk factors associated with C. difficile carriage and the role of the host gut microbiota. Here, we isolated and characterized C. difficile strains from different animal species (predominantly canines (dogs), felines (cats), and equines (horses)) that were brought in for tertiary care at North Carolina State University Veterinary Hospital. C. difficile strains were characterized by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16S rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts. Here, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes including ones known to cause CDI in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridium hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.

Understanding and interpreting community sequencing measurements of the vaginal microbiome.

Community-wide high-throughput sequencing has transformed the study of the vaginal microbiome, and clinical applications are on the horizon. Here we outline the three main community sequencing methods: (1) amplicon sequencing, (2) shotgun metagenomic sequencing, and (3) metatranscriptomic sequencing. We discuss the advantages and limitations of community sequencing generally, and the unique strengths and weaknesses of each method. We briefly review the contributions of community sequencing to vaginal microbiome research and practice. We develop suggestions for critically interpreting research results and potential clinical applications based on community sequencing of the vaginal microbiome. TWEETABLE ABSTRACT: We review the advantages and limitations of amplicon sequencing, metagenomics, and metatranscriptomics methods for the study of the vaginal microbiome.

The afferent vagus and regulation of breathing in response to inhaled CO2 in awake newborn lambs.

Changes in steady state minute ventilation, tidal volume and frequency were determined in unanesthetized lambs before and after bilateral cervical vagotomy while breathing 3, 6, and 9% CO2 in 20% O2 balance N2. The slope of delta VE/delta PaCO2 fell from 0.068 to 0.033 while frequency response depended on intact vagi. Electrical stimulation of the cut proximal vagus (after bilateral vagotomy) restored CO2 responsiveness to control values. From these observations, it may be concluded that the afferent vagus is involved in the control of ventilation during hypercapnia and helps to modulate ventilatory frequency by inhibiting tidal volume.