title: Pharmacodynamics of florfenicol for calf pneumonia pathogens.
abstract: The antimicrobial properties of florfenicol were investigated for the bovine respiratory tract pathogens, Mannheimia haemolytica and Pasteurella multocida. Three in vitro indices of efficacy and potency were determined; minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and in vitro time-kill curves for six pathogenic strains of each organism. Each was monitored in two matrices, Mueller Hinton broth (MHB) and calf serum. MBC:MIC ratios were low, 1.8 : 1 for M haemolytica in both MHB and serum and 2.4 : 1 and 2.1 : 1 for P multocida in MHB and serum, respectively. The killing action of florfenicol had the characteristics of concentration dependency against M haemolytica and codependency (on time and concentration) against P multocida. Modelling of the time-kill data after 24 hours exposure was undertaken to quantify three levels of activity for the ratio, area under concentration-time curve over 24 hours (AUC24h)/MIC; bacteriostatic action (no change in bacterial count), 3log10 reduction and 4log10 reduction in bacterial count. Mean AUC24h/MIC values for P multocida in MHB (and serum) were 22.0 (23.3) hour, 34.5 (39.9) hour and 45.8 (50.4) hour, respectively. Similar numerical values were obtained for M haemolytica. For both bacterial species, interstrain variability was low; coefficients of variation ( per cent) in serum for 3log10 and 4log10 reductions in count were, respectively, 14.3 and 24.1 for P multocida and 7.8 and 11.4 for M haemolytica. These data form a rational basis for dosage selection for treatment of calf pneumonia caused by M haemolytica or P multocida.
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Campus, Hatfield, Herts., AL9 7TA, UK.
authors.forename: J
authors.initials: J
authors.lastname: Illambas
authors.forename: T
authors.initials: T
authors.lastname: Potter
authors.forename: P
authors.initials: P
authors.lastname: Sidhu
authors.forename: A N
authors.initials: AN
authors.lastname: Rycroft
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.forename: P
authors.initials: P
authors.lastname: Lees
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048090:Bovine Respiratory Disease Complex / Q000188:drug therapy / Q000382:microbiology; D002417:Cattle; D015169:Colony Count, Microbial / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D016978:Mannheimia haemolytica / Q000187:drug effects*; D016979:Pasteurella multocida / Q000187:drug effects*; D048089:Pneumonia of Calves, Enzootic / Q000188:drug therapy*; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; C035534:florfenicol; D013839:Thiamphenicol