Persistent effects of ceftriaxone-sulbactam combination on extended-spectrum β-lactamases-producing E. coli

Objective To measure the minimal inhibitory concentration (MIC) and persistent effects of ceftriaxone-sulbactam combination (2∶1) on extended-spectrum β-lactamase-producing E. coli. The persistent effects include post-antibiotic effect (PAE),post-β-lactamase inhibitor effect (PLIE) and post antibiotic sub-MIC effect (PASME).Methods The MIC were determined by broth microdilution method. E. coli strains were exposed to certain concentration of ceftriaxone-sulbactam for 2 hours. The E. coli strains were cultured with various concentrations of antibiotic. The number of colony forming units (CFU) in incubated broth was counted by plating method. The PAE,PLIE and PASME of ceftriaxone-sulbactam on E. coli were calculated according to the logCFU/mL-time (h) curve.Results The MIC of ceftriaxone and ceftriaxone-sulbactam were 256 mg/L and 8/4 mg/L respectively. The PAE of ceftriaxone and ceftriaxone-sulbactam against extended-spectrum β-lactamase-producing E. coli were short or negative. PLIE induced by sulbactam on extended-spectrum β-lactamase-producing E. coli were short or negative at low exposure concentrations of ceftriaxone-sulbactam (2×MIC,4×MIC) and exceeded 6.5 h at 10×MIC.Conclusions The time-dependent ceftriaxone-sulbactam has significant effect on the PLIE of sulbactam against extended-spectrum β-lactamase-producing E. coli,which is concentration-dependent. In addition to increasing the time over MIC,increasing the peak concentration of ceftriaxone-sulbactam may also be beneficial for clinical outcomes of ceftriaxone-sulbactam combination therapy.