The post-exposure response of Enterobacteriaceae to ceftibuten

The responses of ten isolates of Enterobacteriaceae to ceftibuten exposure were monitored by measuring several parameters. Post-antibiotic effect (PAE), control-related effective regrowth time (CERT) and post-antibiotic sub-MIC effect (PA-SME) were determined by bacterial enumeration carried out either by impedance in combination with viable counting (IMP/VC) or by impedance in combination with bioluminescence (IMP/BIOL). Kill curves were carried out by bioluminescence, viable counting and direct microscopy and post-exposure morphology was established. Ceftibuten primarily provoked filamentation. Over 24 h, kill of up to 3.6 log10 was evident by viable counting and direct microscopy at and above the MIC. Minimal kill, of up to 0.26 log10, was shown by bioluminescence. PAE was found to be method dependent, with statistical differences established by Student's t-test. PAE values of up to 0.48 h and 1.47 h (by IMP/BIOL and IMP/VC respectively) were not concentration dependent above 1 x MIC. CERT values were not method dependent, with values of up to 1.71 h also showing a lack of concentration dependence above 1 x MIC. PA-SME may reflect the situation in vivo more accurately than either PAE or CERT. In PAE and CERT studies the antibiotic is eliminated almost immediately, whereas in vivo there is gradual decrease in antibiotic levels. These persisting levels are reflected more accurately by PA-SME. Compared with PAE and CERT, significantly longer values, of up to 7.27 h, were obtained by PA-SME, although this parameter was also found to be method dependent. The results of the PA-SME studies, which may be the most clinically relevant pharmacodynamic parameter, confirm the appropriateness of the current once- or twice-daily dosing schedules despite the lack of PAE.