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This combination therapy involves the co-administration of the monobactam antibiotic aztreonam and the beta-lactamase inhibitor clavulanic acid (typically administered as the fixed-dose combination amoxicillin-clavulanate). Aztreonam is unique among beta-lactams for its stability against metallo-beta-lactamases (MBLs), but it is susceptible to hydrolysis by Class A extended-spectrum beta-lactamases (ESBLs) and Class C AmpC beta-lactamases. By adding clavulanic acid, which inhibits these serine beta-lactamases, the combination restores aztreonam's activity against MBL-producing Enterobacterales that co-produce ESBLs or AmpC. This therapeutic strategy is being investigated by the Centre Hospitalier Universitaire de Nîmes in the Phase 3 ASSET clinical trial as a carbapenem-sparing regimen for the treatment of serious infections, including sepsis and septic shock, particularly in clinical settings with a high prevalence of multi-drug resistant Gram-negative bacteria.
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