Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline

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dc.contributor.authorMaaland, M.
dc.contributor.authorPapich, M.
dc.contributor.authorTurnidge, J.
dc.contributor.authorGuardabassi, L.
dc.date.issued2013
dc.description.abstractDoxycycline 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 ≤0.125 μg/ml. Tetracycline predicted doxycycline susceptibility, but current tetracycline breakpoints were inappropriate for the interpretation of doxycycline susceptibility results. Accordingly, canine-specific doxycycline MIC breakpoints (susceptible, ≤0.125 μg/ml; intermediate, 0.25 μg/ml; resistant, ≥0.5 μg/ml) and zone diameter breakpoints (susceptible, ≥25 mm; intermediate, 21 to 24 mm; resistant, ≤20 mm) and surrogate tetracycline MIC breakpoints (susceptible, ≤0.25 μg/ml; intermediate, 0.5 μg/ml; resistant, ≥1 μg/ml) and zone diameter breakpoints (susceptible, ≥23 mm; intermediate, 18 to 22 mm; resistant, ≤17 mm) were proposed based on the data generated in this study.
dc.description.statementofresponsibilityMarit Gaastra Maaland, Mark G. Papich, John Turnidge, Luca Guardabassi
dc.identifier.citationJournal of Clinical Microbiology, 2013; 51(11):3547-3554
dc.identifier.doi10.1128/JCM.01498-13
dc.identifier.issn0095-1137
dc.identifier.issn1098-660X
dc.identifier.orcidTurnidge, J. [0000-0003-4240-5578]
dc.identifier.urihttp://hdl.handle.net/2440/83453
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.rights© 2013, American Society for Microbiology. All Rights Reserved.
dc.source.urihttps://doi.org/10.1128/jcm.01498-13
dc.subjectAnimals
dc.subjectDogs
dc.subjectStaphylococcus
dc.subjectStaphylococcal Infections
dc.subjectDog Diseases
dc.subjectDoxycycline
dc.subjectTetracycline
dc.subjectAnti-Bacterial Agents
dc.subjectMicrobial Sensitivity Tests
dc.subjectModels, Theoretical
dc.titlePharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline
dc.typeJournal article
pubs.publication-statusPublished

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