{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:20:10Z","timestamp":1760235610902,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>In order to mitigate the food animal sector\u2019s role in the growing threat of antimicrobial resistance (AMR), the World Health Organization (WHO) suggests the use of lower tier antimicrobials, such as florfenicol. Florfenicol has two dosing schemes used to treat primarily bovine respiratory disease. In this study, the objective was to characterize the plasma and gastrointestinal pharmacokinetics of each dosing regimen and assess the effect of these dosing regimens on the prevalence of resistant indicator bacteria over time. Twelve steers underwent abdominal surgery to facilitate the placement of ultrafiltration probes within the lumen of the ileum and colon, as well as placement of an interstitial probe. Following surgery, cattle were dosed with either 20 mg\/kg IM every 48 h of florfenicol given twice (n = 6) or a single, subcutaneous dose (40 mg\/kg, n = 6). Plasma, interstitial fluid, gastrointestinal ultrafiltrate, and feces were collected. Pharmacokinetic analysis demonstrated high penetration of florfenicol within the gastrointestinal tract for both the high and low dose group (300%, 97%, respectively). There was no significant difference noted between dosing groups in proportion or persistence of phenotypically resistant bacterial isolates; however, the percent of resistant isolates was high throughout the study period. The recommendation for the use of a lower tier antimicrobial, such as florfenicol, may allow for the persistence of co-resistance for antibiotics of high regulatory concern.<\/jats:p>","DOI":"10.3390\/microorganisms9091835","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T22:49:51Z","timestamp":1630363791000},"page":"1835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of the Intestinal Pharmacokinetics of Two Different Florfenicol Dosing Regimens and Its Impact on the Prevalence and Phenotypic Resistance of E. coli and Enterococcus over Time"],"prefix":"10.3390","volume":"9","author":[{"given":"Jennifer L.","family":"Halleran","sequence":"first","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryker","family":"Minch","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah J.","family":"Slyvester","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan E.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Prange","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Baynes","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek M.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC 27607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","unstructured":"CDC (2019). Antibiotic Resistance Threats in the United States, 2019, U.S. Department of Health and Human Services, CDC."},{"key":"ref_2","unstructured":"WHO (2021, August 19). Policy on Critically Important Antimicrobials for Human Medicine. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241515528."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1128\/JCM.38.12.4593-4598.2000","article-title":"Characterization of chloramphenicol and florfenicol resistance in Escherichia coli associated with bovine diarrhea","volume":"38","author":"White","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","unstructured":"Riviere, J., and Papich, M.G. (2018). Veterinary Pharmacology and Therapeutics, Wiley-Blackwell. [10th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/jac\/dkab116","article-title":"Genetic features of the poxtA linezolid resistance gene in human enterococci from France","volume":"76","author":"Dejoies","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1089\/mdr.2020.0122","article-title":"Mechanisms of Linezolid Resistance Among Clinical Staphylococcus spp. in Spain: Spread of Methicillin- and Linezolid-Resistant S. epidermidis ST2","volume":"27","author":"Hanke","year":"2021","journal-title":"Microb. Drug Resist."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1128\/AEM.01551-06","article-title":"Antimicrobial-Resistant Enteric Bacteria from Dairy Cattle","volume":"73","author":"Sawant","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1128\/AAC.05360-11","article-title":"Dosing Regimen Matters: The Importance of Early Intervention and Rapid Attainment of the Pharmacokinetic\/Pharmacodynamic Target","volume":"56","author":"Martinez","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/jvp.12236","article-title":"Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria","volume":"39","author":"Foster","year":"2015","journal-title":"J. Veter.-Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Foster, D.M., Jacob, M.E., Farmer, K.A., Callahan, B., Theriot, C.M., Kathariou, S., Cernicchiaro, N., Prange, T., and Papich, M.G. (2019). Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223378"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Foster, D.M., Martin, L.G., and Papich, M.G. (2016). Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159219"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2460\/ajvr.69.8.997","article-title":"Pharmacokinetics of florfenicol in serum and synovial fluid after regional intravenous perfusion in the distal portion of the hind limb of adult cows","volume":"69","author":"Gilliam","year":"2008","journal-title":"Am. J. Veter.-Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1365-2885.2011.01323.x","article-title":"Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection","volume":"35","author":"Holmes","year":"2011","journal-title":"J. Veter.-Pharmacol. Ther."},{"key":"ref_14","unstructured":"FDA (2021, June 28). NARMS Interpretative Criteria for Susceptibility Testing, adopted from CLSI (Clinical and Laboratory Standards Institute) M100-Ed30; 2021, Available online: https:\/\/www.fda.gov\/media\/108180\/download."},{"key":"ref_15","unstructured":"FDA (2021, June 28). NARMS Interpretative Criteria for Susceptibility Testing, adopted from CLSI (Clinical and Laboratory Standards Institute) M100-Ed30; 2012\u20132013, Available online: https:\/\/www.fda.gov\/drugs\/development-resources\/antibacterial-susceptibility-test-interpretive-criteria."},{"key":"ref_16","first-page":"90","article-title":"Pharmacokinetics tricks and traps: Flip-flop models","volume":"1","author":"Boxenbaum","year":"2000","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1365-2885.1994.tb00241.x","article-title":"Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle","volume":"17","author":"Lobell","year":"1994","journal-title":"J. Veter.-Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/jvp.12315","article-title":"Depletion of florfenicol in lactating dairy cows after intramammary and subcutaneous administration","volume":"39","author":"Kawalek","year":"2016","journal-title":"J. Veter.-Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1128\/CMR.00092-12","article-title":"Importance of relating efficacy measures to unbound drug concentrations for anti-infective agents","volume":"26","author":"Gonzalez","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1128\/AEM.01511-15","article-title":"Prevalence of Antimicrobial Resistance and Transfer of Tetracycline Resistance Genes in Escherichia coli Isolates from Beef Cattle","volume":"81","author":"Shin","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40104-016-0127-3","article-title":"Antimicrobial usage and resistance in beef production","volume":"7","author":"Cameron","year":"2016","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.ijmm.2013.03.001","article-title":"Antibiotic resistant enterococci\u2014Tales of a drug resistance gene trafficker","volume":"303","author":"Werner","year":"2013","journal-title":"Int. J. Med. Microbiol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/9\/1835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:55:17Z","timestamp":1760165717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/9\/1835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["microorganisms9091835"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9091835","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2021,8,30]]}}}