Susceptibility Breakpoint for Enrofloxacin against Swine Salmonella spp

Abstract

Susceptibility breakpoints are crucial for prudent use of antimicrobials. This study has developed the first susceptibility breakpoint (MIC < 0.25 g/ml) for enrofloxacin against swine Salmonella spp. based on wild-type cutoff (CO WT ) and pharmacokinetic-pharmacodynamic (PK-PD) cutoff (CO PD ) values, consequently providing a criterion for susceptibility testing and clinical usage of enrofloxacin. Salmonella spp. are leading zoonosis and food-borne pathogens. Approximately 10 to 20% of all human cases of salmonellosis in the European Union may be the result of contact with pigs and consumption of pig meat (1). Enrofloxacin, an FDA-and China-approved fluoroquinolone member, has been used broadly for treatment of swine disease caused by Gram-positive and -negative bacteria. For guiding susceptibility testing and clinical drug usage, the Clinical and Laboratory Standards Institute (CLSI) has developed a susceptibility breakpoint for enrofloxacin in swine for respiratory disease only (2). Before the present study, no breakpoint for enrofloxacin had been established for swine disease caused by enteric bacteria, such as Salmonella.In the present study, 214 swine Salmonella isolates were obtained from five representative districts (Henan, Hubei, Zhejiang, Anhui, and Shanghai) in China during the years 2003 to 2010. The MICs of enrofloxacin to these swine Salmonella isolates were determined by agar dilution susceptibility testing according to the CLSI M31-A3 guidance (2). Primary MIC distribution was subjected to statistical goodness-of-fit tests and nonlinear leastsquares regressions by following the procedure elaborated in a previous study (3). A wild-type cutoff (CO WT ) was developed based on the fitted MIC distribution by following CLSI M37-A3 guidance and some previous methods (3-5).As shown in the primitive enrofloxacin MIC distribution in Fig. 1A, MICs for enrofloxacin against 214 Salmonella isolates were in the range of approximately 0.125 to 8 g/ml. The percentages at each MIC (0.125, 0.25, 0.5, 1, 2, 4, and 8 g/ml) were 6.1%, 0.4%, 14.5%, 15%, 43.5%, 5.6%, and 15%, respectively. The standard goodness-of-fit tests demonstrated that primitive MIC distribution did not match a normal distribution, because a bimodal distribution was observed at MICs of 2 g/ml and 8 g/ml. To obtain unimodal MIC distribution, the 32 Salmonella isolates with a MIC of 8 g/ml were consequently removed. The other 182 swine Salmonella isolates were subsequently subjected to nonlinear least-squares regressions and goodness-of-fit tests. The best fit for the unimodal population was found when presumed MIC distribution was defined as being between 0.125 g/ml and 4.0 g/ ml. In the fitted unimodal MIC distribution (see Fig. 1B), the number of isolates estimated by nonlinear least-squares regression (183 isolates) was closest to the true number of isolates (182 isolates). Of the estimated number of Salmonella strains (183 isolates), more than 95% had enrofloxacin MICs in the range of approximately 0.5 to 2 g/ml. After NORMINV function and NORM...

Susceptibility breakpoint for Danofloxacin against swine Escherichia coli

“…To the best of our knowledge, this is the first study to establish the ECV and CO PD of DANO against E.coli by statistical method. The CO PD (0.03 μg/mL) was much lower than the ECV (8 μg/mL) established in our study, implying that the lower CO PD in our study may be due to the lower dose of drug administration to pigs, because previous studies concluded that the dose of drug administration may affect the PK-PD breakpoint [36–38]. This suggests that (i) more dosing regimens need to be designed in future investigation; (ii) Further studies are needed to illustrate the relationship between DANO non-WT values proposed in this study and its resistant molecular mechanisms.…”

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

“…The MIC 90 values of ENR against swine Camp. jejuni , Salmonella , E. coli , and Lawsonia intracellularis ( L. intracellularis ) that were collected from the literature are provided in Table 3 [ 10 , 11 , 55 , 56 , 57 ]. According to the predicted PK curve, the AUC 24h , C max , and T max of ENR in intestinal contents were 1065.23 μg h/mL, 201.07 μg/mL, and 1.0 h, respectively, at a dose of 5 mg/kg b.w.…”

Antibiotic Resistance Profiles of Salmonella Recovered From Finishing Pigs and Slaughter Facilities in Henan, China

“…Sixteen different molecules of antibiotics belonging to nine classes were used for the MIC assay. The cutoff values recommended by CLSI (CLSI, 2016) except for enrofloxacin (Hao et al, 2013) and colistin (EUCAST, 2019) were used for the categorization of the results (Figure 1). The intermediate category was merged with the resistant ones for the analysis of our data.…”