Moxalactam Disodium

Using an in vitro pharmacokinetic/pharmacodynamics model simulating human intravenous dosing, moxalactam, cefotaxime, and cefoperazone/sulbactam were tested against ESBL‑producing E. coli (CTX‑M‑15) and K. pneumoniae (CTX‑M‑14). Cefotaxime and cefoperazone/sulbactam showed only weak effects, with rapid bacterial regrowth. In contrast, moxalactam produced sustained bactericidal activity (regrowth time >24 h, area between control growth and bactericidal curves >110 log₁₀ CFU/mL·h⁻¹). The authors conclude that moxalactam is a promising alternative for treating infections caused by ESBL‑producing Enterobacteriaceae and warrants further investigation.

Fig. 1 In vitro dynamic time-kill curves using human exposures of moxalactam, cefotaxime, and cefoperazone/sulbactam against Escherichia coli ATCC25922 and CTX-M-producing E. coli and Klebsiella pneumoniae. (Huang C, et al., 2018)

The X‑ray structure of Mox‑1, a plasmid‑mediated class C β‑lactamase that hydrolyzes moxalactam and cefepime, was solved at 1.5 Å resolution. While overall resembling other AmpC enzymes, Mox‑1 shows significant differences in the hydrogen‑bonding network of the substrate‑binding cavity and lacks main‑chain electron density in two regions (residues 214‑216 in the Ω loop and 303‑306 in the B3 β‑strand), indicating structural flexibility. This flexibility likely allows moxalactam to bind without steric clashes, explaining Mox‑1’s unique hydrolytic profile.

Fig. 2 Superposition of Mox-1 and the E. coli AmpC enzyme complexed with moxalactam. (Oguri T, et al., 2014)