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Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Pharmacodynamics of florfenicol for calf pneumonia pathogens
J Illambas1, T Potter, P Sidhu
1Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Campus, Hatfield, Herts., AL9 7TA, UK.
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.
Insights
Florfenicol demonstrates potent antimicrobial activity against bovine respiratory pathogens Mannheimia haemolytica and Pasteurella multocida. These in vitro findings support florfenicol
Area of Science:
- Veterinary Pharmacology
- Antimicrobial Efficacy
- Bovine Respiratory Disease
Background:
- Bovine respiratory disease (BRD) is a significant economic concern in cattle production.
- Mannheimia haemolytica and Pasteurella multocida are primary bacterial pathogens associated with BRD.
- Florfenicol is a broad-spectrum antibiotic used in veterinary medicine.
Purpose of the Study:
- To evaluate the in vitro antimicrobial properties of florfenicol against key BRD pathogens.
- To determine the efficacy and potency of florfenicol using standard microbiological assays.
- To establish a basis for rational florfenicol dosage selection for treating calf pneumonia.
Main Methods:
- Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).
- In vitro time-kill curve analysis of florfenicol against six strains each of M. haemolytica and P. multocida.
- Assessment in Mueller Hinton broth (MHB) and calf serum, with modeling of AUC24h/MIC ratios.
Main Results:
- Low MBC:MIC ratios (≤2.4:1) indicated potent bactericidal activity.
- Florfenicol exhibited concentration-dependent killing of M. haemolytica and time- and concentration-dependent killing of P. multocida.
- Low interstrain variability was observed for both pathogens, with AUC24h/MIC values supporting bacteriostatic and bactericidal effects.
Conclusions:
- Florfenicol possesses significant in vitro antimicrobial activity against M. haemolytica and P. multocida.
- The determined efficacy indices provide a scientific rationale for florfenicol dosage optimization in treating calf pneumonia.
- These findings contribute to effective antimicrobial stewardship in cattle health management.
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