Abstract
BackgroundImproper use of antimicrobials results in poor treatment and severe bacterial resistance. Breakpoints are routinely used in the clinical laboratory setting to guide clinical decision making. Therefore, the objective of this study was to establish antimicrobial susceptibility breakpoints for danofloxacin against Escherichia coli (E.coli), which is an important pathogen of digestive tract infections.ResultsThe minimum inhibitory concentrations (MICs) of 1233 E. coli isolates were determined by the microdilution broth method in accordance with the guidelines in Clinical and Laboratory Standards Institute (CLSI) document M07-A9. The wild type (WT) distribution or epidemiologic cutoff value (ECV) was set at 8 μg/mL with statistical analysis. Plasma drug concentration data were used to establish pharmacokinetic (PK) model in swine. The in vitro time kill test in our study demonstrated that danofloxacin have concentration dependent activity against E.coli. The PK data indicated that danofloxacin concentration in plasma was rapidly increased to peak levels at 0.97 h and remained detectable until 48 h after drug administration. The pharmacodynamic cutoff (COPD) was determined as 0.03 μg/mL using Monte Carlo simulation. To the best of our knowledge, this is the first study to establish the ECV and COPD of danofloxacin against E.coli with statistical method.ConclusionsCompared to the COPD of danofloxacin against E.coli (0.03 μg/mL), the ECV for E.coli seemed reasonable to be used as the final breakpoint of danofloxacin against E.coli in pigs. Therefore, the ECV (MIC ≤8 μg/mL) was finally selected as the optimum danofloxacin susceptibility breakpoint for swine E.coli. In summary, this study provides a criterion for susceptibility testing and improves prudent use of danofloxacin for protecting public health.
Highlights
Improper use of antimicrobials results in poor treatment and severe bacterial resistance
Pathogenic E. coli associated with gastrointestinal disorders have been divided into eight pathotypes based on their virulence profiles: enteropathogenic E. coli (EPEC); enterohaemorrhagic E. coli (EHEC); enterotoxigenic E. coli (ETEC); enteroinvasive E. coli (EIEC); enteroaggregative E. coli (EAEC); diffusely adherent E. coli (DAEC); adherent invasive E. coli (AIEC); and shiga toxin-producing
Epidemiological cut-off values The minimum inhibitory concentrations (MICs) distribution (0.008-128 μg/mL) for DANO was statistically consistent with a normal distribution because the skewness (− 0.321) and kurtosis (− 0.731) were negative
Summary
Improper use of antimicrobials results in poor treatment and severe bacterial resistance. Quinolones, which trap DNA gyrase or topoisomerase IV to form reversible drug enzyme DNA cleavage complexes, to cause bacteriostasis, have a high bioavailability, good tissue penetration, long half-lives, high efficacy, and low incidence of adverse effects. Because of these characteristics, they are widely used against several respiratory and gastrointestinal infections in both humans. Danofloxacin (DANO), a third generation fluoroquinolone antimicrobial drug with rapid bactericidal activity, is often employed to treat colibacillosis in swine via oral or intramuscular administration [9, 10] Their extensive use has serious non-desirable impacts and represents a public health danger. Plasmid-mediated fluoroquinolone resistance genes (qnrS and aac (6′)-Ib-cr) are detected in both patients and pigs in Shandong, China, and these resistance genes can be transmitted horizontally [13]
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