02810naa a2200457 a 450000100080000000500110000800800410001902400590006010000190011924501730013826000090031152014680032065000200178865000260180865000180183465000100185265000180186265000140188065000100189465000190190465000200192365000170194365000140196065000120197465000390198665000190202565000240204465000100206865000140207865300190209270000170211170000200212870000200214870000170216870000200218570000240220570000220222970000170225170000280226877300560229621846042026-02-24       2026    bl uuuu     u00u1 u    #d7 ahttps://doi.org/10.1016/j.smallrumres.2026.1077322DOI1 aLIMA, A. M. C.  aTime-kill curve analysis and pharmacodynamic modeling for in vitro evaluation of cloxacillin activity against Corynebacterium pseudotuberculosis.h[electronic resource]  c2026  aCurrent treatments for Corynebacterium pseudotuberculosis do not result in bacteriological cure and have low biosafety, requiring new therapeutic strategies. This study aimed to establish the tentative epidemiological cutoff (TECOFF) of cloxacillin for Corynebacterium pseudotuberculosis, assess bacterial response through time–kill curves, and identify PK/PD indices and targets describing the antimicrobial-pathogen interaction. The minimum inhibitory concentration (MIC) and time-kill curve were determined in cation-adjusted Miller-Hinton broth and the TECOFF was derived from MIC distribution. A sigmoid Emax model identified the PK/PD index and its targets (PDT) that best described the dose-response profile observed in the time-kill curves. PK/PD targets values were established for bactericidal (E = -3 log10) and eradication (E = -4 log10) activity. MICs for 35 isolates ranged from 4 to 16 µg/mL, with TECOFF of 16 µg/mL (CI 99.9 %). The PK/PD indices %T &gt MIC (R² = 0.85) and AUC/MIC (R² = 0.82) best described the relationship between pharmacokinetic and microbiological parameters, being strongly associated with the effect of cloxacillin against C. pseudotuberculosis. The PDT values were 45 % and 63 % for %T &gt MIC, and 31.79 and 45.5 for AUC48 h/MIC, for bactericidal and eradication activities, respectively. These findings support rational therapeutic protocols and highlight the need for validation in vivo under clinical conditions.  aAnimal diseases  aCaseous lymphadenitis  aGoat diseases  aGoats  aLymphadenitis  aRuminants  aSheep  aSheep diseases  aSmall ruminants  aAntibiótico  aBactéria  aCaprino  aCorynebacterium Pseudotuberculosis  aDoença Animal  aLinfadenite Caseosa  aOvino  aRuminante  aMal do caroço1 aFELIX, L. A.1 aWOSIACKI, S. R.1 aALVES, F. S. F.1 aSOUZA, V. de1 aSOUSA, N. P. de1 aRODRIGUES, M. L. C.1 aBRANDAO, H. de M.1 aFERRANTE, M.1 aFACCIOLI-MARTINS, P. Y.  tSmall Ruminant Researchgv. 258, 107732, May, 2026.