Mutant prevention concentration and mutant selection window for 10 antimicrobial agents against Rhodococcus equi.

This research investigates the efficiency of 10 different antimicrobial drugs and their combinations on Rhodococcus equi bacteria. The study found that the combination of a macrolide with rifampin is most effective at preventing the emergence of resistant mutants.

Research Context

• The research focuses on assessing the mutant prevention concentration (MPC) and mutant selection window for various antimicrobial agents against Rhodococcus equi, a bacterium broadly affecting foals and people worldwide.
• The tested agents – erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline – were chosen based on their in vitro activity and frequency of usage in treating infections caused by R. equi.

Methods and Techniques

• An agar plate assay was used to determine the MPC of each antimicrobial drug and combination, applying them against four virulent strains of R. equi.
• Pharmacodynamic parameters were calculated using available plasma and pulmonary pharmacokinetic variables.
• The bacterium’s response to each agent was observed, specifically focusing on any emerging drug resistance.

Key Findings

• The type of antimicrobial agent significantly affected the MPC. For instance, the MPC of clarithromycin was significantly lower, and the MPC of rifampin and amikacin were significantly higher than other tested agents.
• A combination of macrolides – erythromycin, clarithromycin, or azithromycin – with rifampin led to a considerable decrease in MPC and MPC/MIC ratio, suggesting it is more potent at preventing the development of resistant mutants.
• When combining minimum inhibitory concentration (MIC) and MPC with pharmacokinetic variables, only gentamicin and vancomycin were expected to maintain plasma concentrations above the MPC for a period of time.
• Only clarithromycin and the clarithromycin-rifampin combination were predicted to maintain concentrations in bronchoalveolar cells and pulmonary epithelial lining fluid above the MPC for the entire dosing interval.

Conclusion

• This research indicates that the combination of a macrolide with rifampin holds significant promise in decreasing the emergence of R. equi mutants resistant to treatment.
• Knowledge of each drug’s MPC can inform better treatment strategies, contributing to improving health outcomes in both veterinary and human medicine.