An in vitro study on the pharmacokinetics/pharmacodynamics of ceftriaxone-sul-bactam

Objective To explore the pharmacokinetic/pharmacodynamic characteristics of ceftriaxone-sulbactam (4:1) against ESBLs-producing Enterobacteriaceae strains and evaluate the rationality of the formulation in an in vitro pharmacokinetic/phar-macodynamic (PK/PD) model. Methods The in vitro PK/PD model was established successfully. The PK profiles in humans following a single dose of intravenous administration of ceftriaxone, ceftriaxone-sulbactam (4:1) (synchronously or non-syn-chronously excretion), cefoperazone and cefoperazone-sulbactam (1:1) were simulated in the established model. The bactericidal effect against K. pneumoniae ATCC 700603 (SHV-18 producer), E. coli EC-l (CTX-M-3 producer) and EC-2 (TEM-1 producer) was compared. Results All the five models showed obvious antibacterial activity against E. coli EC-2. The bactericidal effect of ceftriaxone and cefoperazone against K. pneumoniae ATCC 700603 was weak, but the other three compounds demonstrated remarkable antibacterial activity. The maximal efficacy was achieved at 6h. Ceftriaxone and cefoperazone did not have potent bactericidal effect against E. coli EC-l. The bactericidal curves were similar to that of control. The antibacterial activity of cefoperazone-sulbactam and ceftriaxone-sulbactam in non-synchronous models was weak, but the antibacterial activity of ceftriaxone-sulbactam was significantly powerful than others in synchronous model. The bacterial count decreased from 10 6 to 10 1.5 CFU/mL at 6 h after incubation. Conclusions Ceftriaxone-sulbactam (4:1) showed better antibacterial activity in synchronous excretion model than in the nonsynchronous model. The clinical value of ceftriaxone-sulbactam compound is limited. The combination cannot provide meaningful synergistic bactericidal effect.