{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:15:40Z","timestamp":1783131340335,"version":"3.54.6"},"reference-count":27,"publisher":"American Veterinary Medical Association (AVMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of <jats:italic>Mannheimia haemolytica<\/jats:italic> at various bacterial densities and drug concentrations.<\/jats:p>\n<jats:p><jats:bold>SAMPLE<\/jats:bold> 4 unique isolates of <jats:italic>M haemolytica<\/jats:italic> recovered from clinically infected cattle.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. <jats:italic>Mannheimia haemolytica<\/jats:italic> suspensions (10<jats:sup>6<\/jats:sup> to 10<jats:sup>9<\/jats:sup> CFUs\/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log<jats:sub>10<\/jats:sub> reduction in viable cells (percentage of cells killed) was measured at various points.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of <jats:italic>M haemolytica<\/jats:italic> by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.<\/jats:p>","DOI":"10.2460\/ajvr.76.10.860","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T14:50:52Z","timestamp":1443451852000},"page":"860-868","source":"Crossref","is-referenced-by-count":16,"title":["Bactericidal effects of various concentrations of enrofloxacin, florfenicol, tilmicosin phosphate, and tulathromycin on clinical isolates of Mannheimia haemolytica"],"prefix":"10.2460","volume":"76","author":[{"given":"Joseph M.","family":"Blondeau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantelle D.","family":"Shebelski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine K.","family":"Hesje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Evidence to support the rationale that bacterial eradication in respiratory tract infection is an important aim of antimicrobial therapy","first-page":"129","volume":"47","author":"Dagan","year":"2001"},{"key":"ref2","series-title":"Calf pneumonia","first-page":"237","volume":"1","author":"Bryson","year":"1985"},{"key":"ref3","series-title":"Dairy calf pneumonia: the disease and its impact","first-page":"379","volume":"13","author":"Ames","year":"1997"},{"key":"ref4","series-title":"Involvement of microbial respiratory pathogens in acute interstitial pneumonia in feedlot cattle","first-page":"1519","volume":"62","author":"Loneragan","year":"2001"},{"key":"ref5","series-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically","year":"2009"},{"key":"ref6","series-title":"Mutant prevention concentrations (MPC) of fluoroquinolones for clinical isolates of Streptococcus pneumoniae","first-page":"433","volume":"45","author":"Blondeau","year":"2001"},{"key":"ref7","series-title":"The role of PK\/PD parameters to avoid selection and increase of resistance: mutant prevention concentration","first-page":"1","volume":"16","author":"Blondeau","year":"2004"},{"key":"ref8","series-title":"New concepts in antimicrobial susceptibility testing: the mutant prevention concentration and mutant selection window approach","first-page":"383","volume":"20","author":"Blondeau","year":"2009"},{"key":"ref9","series-title":"Minimal inhibitory and mutant prevention concentrations for azithromycin, clarithromycin and erythromycin with clinical isolates of Streptococcus pneumoniae","first-page":"631","volume":"68","author":"Metzler","year":"2013"},{"key":"ref10","series-title":"Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine isolates of Mannheimia haemolytica","first-page":"85","volume":"160","author":"Blondeau","year":"2012"},{"key":"ref11","series-title":"The specific polysaccharide content of pneumonic lungs","first-page":"505","volume":"76","author":"Frisch","year":"1942"},{"key":"ref12","series-title":"Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Use of the protected specimen brush technique in 54 mechanically ventilated patients","first-page":"1004","volume":"142","author":"Fagon","year":"1990"},{"key":"ref13","series-title":"Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis","first-page":"549","volume":"88","author":"Feldman","year":"1976"},{"key":"ref14","series-title":"Bacterial counts in cerebrospinal fluid of children with meningitis","first-page":"278","volume":"9","author":"Bingen","year":"1990"},{"key":"ref15","series-title":"Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals","year":"2013"},{"key":"ref16","series-title":"Optimal killing of Streptococcus pneumoniae by gemifloxacin, levofloxacin and moxifloxacin","author":"Blondeau"},{"key":"ref17","series-title":"Application of two methods to determine killing of Streptococcus pneumoniae by various fluoroquinolones","first-page":"366","volume":"18","author":"Blondeau","year":"2006"},{"key":"ref18","series-title":"The epidemiology of bovine respiratory disease: what is the evidence for predisposing factors?","first-page":"1095","volume":"51","author":"Taylor","year":"2010"},{"key":"ref19","series-title":"The bovine respiratory disease complex","first-page":"233","volume":"15","author":"Lillie","year":"1974"},{"key":"ref20","series-title":"An evaluation of bovine respiratory disease complex in feedlot cattle: impact on performance and carcass traits using treatment records and lung lesion scores","first-page":"1821","volume":"87","author":"Schneider","year":"2009"},{"key":"ref21","series-title":"A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes","first-page":"639","volume":"24","author":"Wilson","year":"2002"},{"key":"ref22","series-title":"Efficacy of oral ciprofloxacin vs clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis","first-page":"730","volume":"27","author":"Chodosh","year":"1998"},{"key":"ref23","series-title":"Predicting antimicrobial resistance in invasive pneumococcal infections","first-page":"1288","volume":"40","author":"Vanderkooi","year":"2005"},{"key":"ref24","series-title":"Bactericidal properties of moxifloxacin and post-antibiotic effect","first-page":"43","volume":"43","author":"Boswell","year":"1999"},{"key":"ref25","series-title":"Chapter 5: drug selection and optimization of dosage schedules to minimize antimicrobial resistance","first-page":"49","author":"Lees","year":"2006"},{"key":"ref26","series-title":"Mutant prevention concentration of gemifloxacin for clinical isolates of Streptococcus pneumoniae","first-page":"440","volume":"47","author":"Hansen","year":"2003"},{"key":"ref27","series-title":"Effect of fluoroquinolone concentration on selection of resistant mutants of Mycobacterium bovis BCG and Staphylococcus aureus","first-page":"1756","volume":"43","author":"Dong","year":"1999"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/76\/10\/ajvr.76.10.860.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/76\/10\/ajvr.76.10.860.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/76\/10\/ajvr.76.10.860.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:36:38Z","timestamp":1741350998000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/76\/10\/ajvr.76.10.860.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":27,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.76.10.860","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2015,10]]}}}