Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation

Objectives The aim of this study was to evaluate the bactericidal effects of moxalactam (MOX), cefotaxime (CTX), and cefoperazone/sulbactam (CFZ/SBT) against extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, using an in vitro pharmacokinetics (PK)/pharmacodynamics model. Methods Two clinical ESBL-producing strains (blaCTX-M-15 positive E. coli 3376 and blaCTX-M-14 positive K. pneumoniae 2689) and E. coli American Type Culture Collection (ATCC)25922 were used in the study. The PK Auto Simulation System 400 was used to simulate the human PK procedures after intravenous administration of different doses of MOX, CTX, and CFZ/SBT. Bacterial growth recovery time (RT) and the area between the control growth curve and bactericidal curves (IE) were employed to assess the antibacterial efficacies of all the agents. Results The minimum inhibitory concentrations of MOX, CTX, and CFZ/SBT against E. coli ATCC25922, 3376, and 2689 strains were 0.5, 0.5, 0.25; 0.06, >256, 256; and 0.5/0.5, 16/16, 32/32 mg/L. All the agents demonstrated outstanding bactericidal effects against E. coli ATCC25922 (RT >24 h and IE >120 log10 CFU/mL·h-1) with simulating PK procedures, especially in the multiple dose administration models. Against ESBL producers, CTX and CFZ/SBT displayed only weak bactericidal effects, and subsequent regrowth was evident. MOX exhibited potent antibacterial activity against all the strains tested. The values of effective parameters of MOX were much higher than those of CTX and CFZ/SBT (the bacterial RTs with the 3 agents were >24, <4, and <13 h, and the IEs were >110, <10, and <60 log10 CFU/mL·h-1, respectively). Conclusion MOX demonstrated excellent bactericidal effect, which is worthy of further exploration to serve as an alternative therapeutic agent against ESBL-producing Enterobacteriaceae.