Danofloxacin Treatment Alters the Diversity and Resistome Profile of Gut Microbiota in Calves

Beyi, Ashenafi Feyisa; Brito-Goulart, Debora; Hawbecker, Tyler; Slagel, C.; Ruddell, Brandon; Hassall, Alan; Dewell, Reneé D.; Dewell, Grant A.; Şahin, Orhan; Zhang, Qijing; Plummer, Paul J.

doi:10.3390/microorganisms9102023

Cited by 12 publications

(14 citation statements)

References 74 publications

(114 reference statements)

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“…We observed that the microbiome diversity of treated cattle was significantly disturbed in the short term, increasing ARGs conferring resistance to tetracyclines compared to control animals without exposure to OTC. This finding is consistent with previous studies that reported the perturbation of the gut microbiome following antibiotic treatment within a few days after antibiotic exposure [ 25 , 26 , 27 ].…”

Section: Discussionsupporting

confidence: 93%

Short-Term Impact of Oxytetracycline Administration on the Fecal Microbiome, Resistome and Virulome of Grazing Cattle

Rovira

2023

Antibiotics

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Antimicrobial resistance (AMR) is an important public health concern around the world. Limited information exists about AMR in grasslands-based systems where antibiotics are seldom used in beef cattle. The present study investigated the impacts of oxytetracycline (OTC) on the microbiome, antibiotic resistance genes (ARGs), and virulence factor genes (VFGs) in grazing steers with no previous exposure to antibiotic treatments. Four steers were injected with a single dose of OTC (TREAT), and four steers were kept as control (CONT). The effects of OTC on fecal microbiome, ARGs, and VFGs were assessed for 14 days using 16S rRNA sequencing and shotgun metagenomics. Alpha and beta microbiome diversities were significantly affected by OTC. Following treatment, less than 8% of bacterial genera had differential abundance between CONT and TREAT samples. Seven ARGs conferring resistance to tetracycline (tet32, tet40, tet44, tetO, tetQ, tetW, and tetW/N/W) increased their abundance in the post-TREAT samples compared to CONT samples. In addition, OTC use was associated with the enrichment of macrolide and lincosamide ARGs (mel and lnuC, respectively). The use of OTC had no significant effect on VFGs. In conclusion, OTC induced short-term alterations of the fecal microbiome and enrichment of ARGs in the feces of grazing beef cattle.

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Section: Discussionsupporting

confidence: 93%

Short-Term Impact of Oxytetracycline Administration on the Fecal Microbiome, Resistome and Virulome of Grazing Cattle

Rovira

2023

Antibiotics

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“…Subcutaneously administered enrofloxacin to calves achieved the intestinal concentration that could decrease intestinal bacteria 42 . Further, our metagenomic studies 21 , 22 have revealed that the fecal microbial diversity has been significantly changed in calves; some bacterial taxa responded differently to the low and high enrofloxacin doses. The fecal resistome profiles have been affected remarkably in FQs administered groups compared to the control groups 21 , 22 .…”

Section: Discussionmentioning

confidence: 84%

“…On the eighth day, both groups were administered a single dose of danofloxacin (8 mg/kg body weight, ADVOCIN™, danofloxacin mesylate , Pfizer Animal Health) in the neck, subcutaneously. The animal study was described in more detail in our recent publication 21 .…”

Section: Methodsmentioning

confidence: 99%

Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves

Beyi

Mochel

Magnin

et al. 2022

Sci Rep

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Danofloxacin and enrofloxacin are fluoroquinolones (FQs) used to treat and control bovine respiratory disease (BRD) complex. While low toxicity, high bactericidal activity, and availability in single and multiple dosing regimens make them preferable, the increasing incidence of FQ-resistance in foodborne pathogens and effects on gut microbiota necessitate evaluating their pharmacokinetics (PKs). The objective of this study was to determine the exposure level of gut microbiota to subcutaneously administered FQs and compare their PKs between plasma and feces in healthy and Mannheimia haemolytica infected calves. A single dose of danofloxacin (8 mg/kg), low dose (7.5 mg/kg), or high dose (12.5 mg/kg) of enrofloxacin was administered to calves. Blood and feces were collected from calves under experimental conditions over 48 h, and FQ concentrations were measured using Ultra High-Pressure Liquid Chromatography. While moderate BRD signs were exhibited in most calves in the infected cohorts, the plasma PKs were similar between healthy and sick calves. However, the fecal danofloxacin concentration was lower in the BRD group (area under concentration–time curve [AUCinf], BRD median = 2627, healthy median = 2941 h*μg/mL, adj.P = 0.005). The dose normalized plasma and fecal danofloxacin concentrations were higher than those of enrofloxacin and its metabolite ciprofloxacin. Further, FQs had several fold higher overall concentrations in feces than in plasma in both groups. In conclusion, parenterally administered FQs expose gut microbiota to high concentrations of the antibiotics.

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“…Both experimental and observational studies indicated that antibiotic use and thus, the resultant selection pressure is an important factor driving the emergence and persistence of ARB and their resistance genes [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Mastitis is the most frequent disease of dairy cattle; and ceftiofur is the most commonly used antimicrobial drug used to manage it [ 5 , 68 ].…”

Section: Use Of Beta-lactam Antibiotics In the Usa Dairy Cattle Farmsmentioning

confidence: 99%

Extended-Spectrum Beta-Lactamases Producing Enterobacteriaceae in the USA Dairy Cattle Farms and Implications for Public Health

Gelalcha

Dego

2022

Antibiotics

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Antimicrobial resistance (AMR) is one of the top global health threats of the 21th century. Recent studies are increasingly reporting the rise in extended-spectrum beta-lactamases producing Enterobacteriaceae (ESBLs-Ent) in dairy cattle and humans in the USA. The causes of the increased prevalence of ESBLs-Ent infections in humans and commensal ESBLs-Ent in dairy cattle farms are mostly unknown. However, the extensive use of beta-lactam antibiotics, especially third-generation cephalosporins (3GCs) in dairy farms and human health, can be implicated as a major driver for the rise in ESBLs-Ent. The rise in ESBLs-Ent, particularly ESBLs-Escherichia coli and ESBLs-Klebsiella species in the USA dairy cattle is not only an animal health issue but also a serious public health concern. The ESBLs-E. coli and -Klebsiella spp. can be transmitted to humans through direct contact with carrier animals or indirectly through the food chain or via the environment. The USA Centers for Disease Control and Prevention reports also showed continuous increase in community-associated human infections caused by ESBLs-Ent. Some studies attributed the elevated prevalence of ESBLs-Ent infections in humans to the frequent use of 3GCs in dairy farms. However, the status of ESBLs-Ent in dairy cattle and their contribution to human infections caused by ESBLs-producing enteric bacteria in the USA is the subject of further study. The aims of this review are to give in-depth insights into the status of ESBL-Ent in the USA dairy farms and its implication for public health and to highlight some critical research gaps that need to be addressed.

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Danofloxacin Treatment Alters the Diversity and Resistome Profile of Gut Microbiota in Calves

Cited by 12 publications

References 74 publications

Short-Term Impact of Oxytetracycline Administration on the Fecal Microbiome, Resistome and Virulome of Grazing Cattle

Short-Term Impact of Oxytetracycline Administration on the Fecal Microbiome, Resistome and Virulome of Grazing Cattle

Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves

Extended-Spectrum Beta-Lactamases Producing Enterobacteriaceae in the USA Dairy Cattle Farms and Implications for Public Health

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