{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:42:57Z","timestamp":1788374577735,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Pasteurella multocida<\/jats:italic> is a key bacterial agent involved in most respiratory disorders in rabbits. The objective of this study was to evaluate the risk of selecting <jats:italic>Pasteurella multocida<\/jats:italic> strains resistant to enrofloxacin (ENRO) in food producing rabbits treated with ENRO via drinking water, according to the standard husbandry practices. Indeed, despite the EU community guidelines recommend a prudent use of antibiotics and promote new strategies to prevent bacterial diseases, antimicrobial therapy remains the primary approach for pasteurellosis management in rabbits. Therefore, the potential risk of selecting resistant bacteria in food-producing animals requires identifying optimized dosage regimens to minimize resistance emergence and to extend the useful lifetime of the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we isolated <jats:italic>Pasteurella multocida<\/jats:italic> strains from bacterial colonies sampled in nasal swabs collected from 6 healthy rabbits and 12 rabbits suffering respiratory disorders. Animals were sourced from industrial farms and were randomly selected to investigate the inter-individual variability in antimicrobial exposure associated with treatment via drinking water. Sick rabbits underwent an approved ENRO treatment (10\u202fmg\/kg for 5\u202fdays) administered via drinking water, following standard husbandry practices. We investigated the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC), and the mutant prevention concentration (MPC) of ENRO against bacterial strains in healthy rabbits and in sick rabbits before and after treatment. We recorded plasma drug concentrations of treated animals, and we applied the mutant selection window (MSW) approach to each subject. Finally, we calculated the PK\/PD indices for concentration-dependent antimicrobials to assess ENRO\u2019s clinical efficacy and it\u2019s potential for promoting resistance using published pharmacokinetic (PK) parameters and maximum drug plasma concentrations recorded in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we showed that treatment with ENRO improved clinical signs in rabbits with pasteurellosis but failed to completely eradicate the pathogen, consistent with previous studies. MPC-based analysis showed acquired resistance and potential ENRO-induced shift to a lesser sensitivity in the <jats:italic>P. multocida<\/jats:italic> population. Moreover, MSW analysis revealed that 45% of treated rabbits exhibited potential for drug resistance selection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that the current ENRO dosing regimen for pasteurellosis in rabbits is inadequate and may contribute to resistance development.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2025.1474409","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:44:44Z","timestamp":1739443484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Simulation of a field condition to evaluate the risk of enrofloxacin-resistant Pasteurella multocida strain selection in food producing rabbits treated via drinking water"],"prefix":"10.3389","volume":"12","author":[{"given":"Elena","family":"Circella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Lucatello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Montanucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Belloli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Capolongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/s0195-5616(00)06009-5","article-title":"Respiratory diseases of rodents and rabbits","volume":"30","author":"Langan","year":"2000","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.cvex.2021.01.006","article-title":"Respiratory disorders in rabbits","volume":"24","author":"Jekl","year":"2021","journal-title":"Vet Clin Exot Anim"},{"key":"ref3","first-page":"121","article-title":"The bacterial flora of the upper respiratory tract of normal rabbits","volume":"57","author":"Ajuwape","year":"2002","journal-title":"Israel J Vet Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.vetmic.2006.02.003","article-title":"Epidemiology and susceptibility of pathogenic bacteria responsible for upper respiratory tract infections in pet rabbits","volume":"115","author":"Rougier","year":"2006","journal-title":"Vet Microbiol"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1002\/9780470693780","volume-title":"Rabbits: Health, husbandry and diseases","author":"Richardson","year":"2000"},{"key":"ref6","volume-title":"Critically important antimicrobials for human medicine, 6th revision","year":"2018"},{"key":"ref7","year":"2019"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1258\/002367790780865994","article-title":"In vivo activity of orally administered antibiotics and chemotherapeutics against acute septicaemic pasteurellosis in rabbits","volume":"24","author":"Okerman","year":"1990","journal-title":"Lab Anim"},{"key":"ref9","first-page":"572","article-title":"Efficacy of enrofloxacin in the treatment of respiratory pasteurellosis in rabbits","volume":"41","author":"Broome","year":"1991","journal-title":"Lab Anim Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"40","DOI":"10.4236\/ojvm.2016.62006","article-title":"A review of Enrofloxacin for veterinary use","volume":"6","author":"Trouchon","year":"2016","journal-title":"Open J Vet Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.vetmic.2019.07.017","article-title":"Antimicrobial resistance of Pasteurella multocida isolated from diseased food producing animals and pets","volume":"235","author":"Bour\u00e9ly","year":"2019","journal-title":"Vet Microbiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1007\/s40262-019-00791-z","article-title":"What antibiotic exposures are required to suppress the emergence of resistance for gram-negative Bacteria? 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