AAI101 是一种广谱β-lactamase抑制剂，有抗耐药革兰氏阴性细菌。

AAI101 is an extended-spectrum β-lactamase inhibitor for the treatment of multi-drug resistant gram-negative bacterial infections.

AAI101, a novel extended-spectrum β-lactamase inhibitor.?Of the 223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49% ertapenem non-susceptible, 57% piperacillin/tazobactam non-susceptible, 90% were multidrug-resistant (resistant to 3 drug classes), 22% produced carbapenemases, and 67% produced ESBLs.?Addition of AAI101 restored the activity of cefepime such that the MIC50 was reduced from >64 mg/L for cefepime to 0.13 mg/L for cefepime/AAI101, supporting its continued development treatment for infections caused by these organisms.AAI101 shows potent activity against specific resistance phenotypes with MIC50 and MIC90 of 0.125 mg/L and 64 mg/L[1].?Cefepime-AAI101 MICs decreases with increasing concentrations of AAI101 (over the range from 1 to 16 mg/L) for most strains.?which is demonstrating a concentration dependence of AAI101 on restoration of the antibacterial activity of the cephalosporin[1].

Against a panel of 20 mostly carbapenemase-producing cefepime-nonsusceptible strains of the family Enterobacteriaceae, we evaluated the MICs of cefepime in the presence of various fixed AAI101 concentrations (1, 2, 4, 8, and 16 mg/liter) and the in vivo efficacy of simulated human doses of cefepime and cefepime-AAI101 in a neutropenic murine thigh infection model.?At 2 h after inoculation, mice were dosed with regimens that provided a profile mimicking the free drug concentration-time profile observed in humans given cefepime at 2 g every 8 h (q8h;?as a 30-min infusion) or cefepime-AAI101 at 2 g/0.5 g q8h (as a 30-min infusion).?Efficacy was determined by calculation of the change in thigh bacterial density (log10 number of CFU) after 24 h relative to the starting inoculum (0 h). After 24 h, bacterial growth of 2.7 0.1 log10 CFU (mean standard error) was observed in control animals.?Efficacy for cefepime monotherapy was observed against only 3 isolates, whereas increases in bacterial density similar to that in the control animals were noted for the remaining 17 strains (all with cefepime MICs of 64 mg/liter).?The humanized cefepime-AAI101 dosing regimen resulted in bacterial reductions of 0.5 log10 CFU for 12 of the 20 strains[2].

1001404-83-6

C11H14N4O5S

314.32

AAI101

DMSO:113.3 mg/mL (360.46 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years