PMID- 23966509 OWN - NLM STAT- MEDLINE DCOM- 20140331 LR - 20211021 IS - 1098-660X (Electronic) IS - 0095-1137 (Print) IS - 0095-1137 (Linking) VI - 51 IP - 11 DP - 2013 Nov TI - Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline. PG - 3547-54 LID - 10.1128/JCM.01498-13 [doi] AB - Doxycycline is a tetracycline that has been licensed for veterinary use in some countries, but no clinical breakpoints are available for veterinary pathogens. The objectives of this study were (i) to establish breakpoints for doxycycline and (ii) to evaluate the use of tetracycline as a surrogate to predict the doxycycline susceptibility of Staphylococcus pseudintermedius isolates. MICs and inhibition zone diameters were determined for 168 canine S. pseudintermedius isolates according to Clinical and Laboratory Standards Institute (CLSI) standards. Tetracycline resistance genes were detected by PCR, and time-kill curves were determined for representative strains. In vitro pharmacodynamic and target animal pharmacokinetic data were analyzed by Monte Carlo simulation (MCS) for the development of MIC interpretive criteria. Optimal zone diameter breakpoints were defined using the standard error rate-bounded method. The two drugs displayed bacteriostatic activity and bimodal MIC distributions. Doxycycline was more active than tetracycline in non-wild-type strains. MCS and target attainment analysis indicated a certainty of >/= 90% for attaining an area under the curve (AUC)/MIC ratio of >25 with a standard dosage of doxycycline (5 mg/kg of body weight every 12 h) for strains with MICs of /= 0.5 mug/ml) and zone diameter breakpoints (susceptible, >/= 25 mm; intermediate, 21 to 24 mm; resistant, /= 1 mug/ml) and zone diameter breakpoints (susceptible, >/= 23 mm; intermediate, 18 to 22 mm; resistant,