Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media

L Dorey,S Hobson,P Lees

doi:10.1016/j.rvsc.2016.11.001

Abstract

Pharmacodynamic properties of marbofloxacin were established for six isolates each of the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Three in vitro indices of potency were determined; Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Mutant Prevention Concentration (MPC). For MIC determination Clinical Laboratory Standards Institute guidelines were modified in three respects: (1) comparison was made between two growth media, an artificial broth and pig serum; (2) a high inoculum count was used to simulate heavy clinical bacteriological loads; and (3) five overlapping sets of two-fold dilutions were used to improve accuracy of determinations. Similar methods were used for MBC and MPC estimations. MIC and MPC serum:broth ratios for A. pleuropneumoniae were 0.79:1 and 0.99:1, respectively, and corresponding values for P. multocida were 1.12:1 and 1.32:1. Serum protein binding of marbofloxacin was 49%, so that fraction unbound (fu) serum MIC values were significantly lower than those predicted by correction for protein binding; fu serum:broth MIC ratios were 0.40:1 (A. pleuropneumoniae) and 0.50:1 (P. multocida). For broth, MPC:MIC ratios were 13.7:1 (A. pleuropneumoniae) and 14.2:1 (P. multocida). Corresponding ratios for serum were similar, 17.2:1 and 18.8:1, respectively. It is suggested that, for dose prediction purposes, serum data might be preferable to potency indices measured in broths.

Highlights

Accepted methods, guidelines and standards for Minimum Inhibitory Concentration (MIC) determination have been set by the European Union Committee on Antimicrobial Sensitivity testing (EUCAST) and the Clinical Laboratory Standards Institute (CLSI)
3.2.Minimum Inhibitory, Minimum Bactericidal and Mutant Prevention Concentrations Table 2 presents data as geometric means (SD) for MIC, Minimum Bactericidal Concentration (MBC) and MPC for broth, serum and serum values corrected for protein binding
The possible causes of these trends may be that at low antimicrobial drug concentrations where the isolates are susceptible, these tests may be influenced by the culture media and environmental conditions, these external conditions may not be so influential at high drug concentrations. 4.3 Conclusions The present study reports comparative MIC, MBC and MPC data for two growth matrices, broth and pig serum for the pig pneumonia pathogens, A. pleuropneumoniae and P. multocida

Summary

Introduction

Accepted methods, guidelines and standards for Minimum Inhibitory Concentration (MIC) determination have been set by the European Union Committee on Antimicrobial Sensitivity testing (EUCAST) and the Clinical Laboratory Standards Institute (CLSI). CLSI reports microbiological Cut-Offs (COWT) and EUCAST reports Epidemiological Cut-Offs (ECOFF) These are often identical but differences occur for some drugs. The CLSI/EUCAST standards are based on the use of broths, formulated to facilitate bacterial growth in vitro. They differ in composition from biological fluids and may not reflect bacterial growth conditions in vivo. To enable comparisons between broths and biological fluids as growth matrices, and to evaluate possible differences between them, previous authors have used serum, plasma and inflammatory exudate

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Discussion

Conclusion