Pharmacokinetics/pharmacodynamics analysis of trimethoprim and sulfamethoxazole for methicillin-resistant Staphylococcus aureus infection after intravenous and per os administration in Thoroughbred horses

Objective

A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the dosage regimens of trimethoprim/sulfamethoxazole for methicillin-resistant Staphylococcus aureus (MRSA) infections after intravenous (IV) and per os (PO) administration in horses.

Methods

Trimethoprim/sulfamethoxazole plasma concentrations were measured in six horses after a single IV administration of 15 mg/kg (2.5 mg/kg trimethoprim and 12.5 mg/kg sulfamethoxazole) and PO administration of 30 mg/kg (5.0 mg/kg trimethoprim and 25.0 mg/kg sulfamethoxazole). The data were modeled using a nonlinear mixed-effects model. The probability of target attainment (PTA) of the PK/PD target defined as the ratio of the area under the free plasma concentration-time curve to the minimum inhibitory concentration (MIC) over 25 h was calculated for 5000 horses using Monte Carlo simulations.

Results and conclusion

Trimethoprim/sulfamethoxazole dosage regimens of 15 mg/kg IV and 30 mg/kg PO at the approved interval of q12h did not attain therapeutic targets for MRSA infections in horses. More frequent administration (q8h) may be necessary to achieve these targets. In addition, this standard dosage achieved only 90 % PTA against the MIC of 0.125/2.38 mg/L and did not achieve against the MIC for the CLSI breakpoint for humans (2.0/38 mg/L).