{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:28:11Z","timestamp":1787509691502,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a \u201cmoving target\u201d along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Rhodococcus equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    infection in foals, for nearly 40\u2009years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>R. equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    minimum inhibitory concentrations (MICs), as well as better efficacy, compared with other approaches, and limiting the rate of antimicrobial resistance to either single agent. However, rifampin acts as a perpetrator drug for many co\u2010administered drugs. This critical review evaluates the available evidence for rifampin use in foals with\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>R. equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    , concerning pharmacokinetic\/pharmacodynamic characteristics of rifampin in foals, in\u00a0vitro microbiological studies and selection of antimicrobial resistance, as well as an analysis of randomized clinical trials. Rifampin is a nuclear pregnane X receptor activator, which results in strong negative drug interactions towards itself and other drugs, for drug\u2010absorption routes either by upregulation of presystemic elimination mechanisms (e.g., intestinal and hepatic CYP3A4), or functional drug\u2010absorption carriers (e.g., intestinal P\u2010glycoprotein) and\/or inhibition of intestinal and\/or hepatic drug\u2010uptake carriers (e.g., OATP1B1, OATP2B1, MRP2). Chronic rifampin administration results in decreases in the serum and target site\/s concentrations of many parent drugs, including itself. Rifampin concomitant therapies do not demonstrate a significant advantage over monotherapy with macrolides, in randomized controlled blinded and double\u2010blinded clinical trials for subclinical, and mild\u2010to\u2010moderate bronchopneumonia in foals with pulmonary abscesses, regardless of initial pulmonary abscess score. Efficacy of rifampin concomitant therapies for severe\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Rhodococcus equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    pneumonia has not been fully investigated, but there is sufficient accumulated evidence in foals to raise major concerns about the incorrect use of rifampin in equine medicine. These concerns include rifampin as a bacteriostatic antibiotic against\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>R. equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    , with changing pharmacokinetics during treatment that decreases parent\/coparent concentrations as well as the risk of selecting for multi\u2010resistant\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>R. equi<\/jats:italic>\n                    <\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/jvp.70007","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T08:40:19Z","timestamp":1750754419000},"page":"345-358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Is Rifampin (Rifampicin) Essential for the Treatment of\n                    <i>Rhodococcus equi<\/i>\n                    Infections in Foals? A Critical Review of the Role of Rifampin"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9694-1400","authenticated-orcid":false,"given":"Keith Edward","family":"Baptiste","sequence":"first","affiliation":[{"name":"Danish Medicines Agency  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels Christian","family":"Kyvsgaard","sequence":"additional","affiliation":[{"name":"Danish Medicines Agency  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Omar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology Faculty of Veterinary Medicine, University of Tripoli  Tripoli Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Damborg","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences Faculty of Health and Medical Sciences, University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Dowling","sequence":"additional","affiliation":[{"name":"Western College of Veterinary Medicine  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201057479\u20109"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02260\u201019"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw080"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2013.07.006"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.12662"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00907"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.12796"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13567"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21995"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/2046\u20100481\u201060\u201012\u2010728"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.1985.46.02.442"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102885.1992.tb01021.x"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102885.1992.tb00999.x"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1902.121210"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2016.1222640"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01121\u201014"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2011.02.004"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13508"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.8.2784\u20102787.2001"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.1990.197.01.114"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.022285"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00042"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.arba\u20100004\u20102016"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.237.1.74"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2012.05.031"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6663"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1517\u201083822014000200040"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20103306.1997.tb03129.x"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci11020092"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jevs.2023.104845"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12504"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20101135(87)90121\u20100"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2019.07.010"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/1462\u20102920.15020"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1458496"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102885.1993.tb00156.x"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13871"},{"key":"e_1_2_14_39_1","unstructured":"McCracken J. 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