AUTHOR=Zhou Yu-Feng , Shi Wei , Yu Yang , Tao Meng-Ting , Xiong Yan Q. , Sun Jian , Liu Ya-Hong 

TITLE=Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.01513

DOI=10.3389/fmicb.2015.01513

ISSN=1664-302X

ABSTRACT=<p>Biofilm formations play an important role in <italic>Staphylococcus aureus</italic> pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to <italic>S. aureus</italic>, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and <italic>in vitro</italic> time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study <italic>S. aureus</italic> strains. The <italic>in vivo</italic> post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid <italic>E</italic><sub>max</sub> model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four <italic>S. aureus</italic> strains were 0.5 and 16 μg/mL, respectively. The BBCs (32–64 μg/mL) and MBECs (64–256 μg/mL) of these study strains were much higher than their corresponding BPC values (1–2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (<italic>f</italic>T &gt; MIC, <italic>R</italic><sup>2</sup> = 96.2%) and the MBIC (<italic>f</italic>T &gt; MBIC, <italic>R</italic><sup>2</sup> = 94.7%), respectively. In addition, the AUC<sub>24h</sub>/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (<italic>R</italic><sup>2</sup> = 93.1%). The values of AUC<sub>24h</sub>/MBIC for biofilm-static and 1-log<sub>10</sub>-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating <italic>S. aureus</italic> biofilm-related infections.</p>