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**Ceftazidime-avibactam + fosfomycin** is an investigational combination therapy comprising two antibiotic agents—**ceftazidime-avibactam (CZA)** (a third-generation cephalosporin plus a non-β-lactam β-lactamase inhibitor), and **fosfomycin** (a phosphonic acid derivative). This combination is under development for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, particularly multidrug-resistant Pseudomonas aeruginosa and Escherichia coli. - **Mechanism of Action:** - **Ceftazidime** acts by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (mainly PBP3) leading to bacterial cell death[2][4][6]. - **Avibactam** inhibits class A, C, and some D β-lactamases, thereby protecting ceftazidime from enzymatic degradation and extending its antibacterial spectrum[4]. - **Fosfomycin** inhibits the early stage of bacterial cell wall synthesis by inactivating the enzyme MurA[5]. - **Synergy:** - The combination demonstrates **synergistic bactericidal activity** against multidrug-resistant strains, significantly reducing bacterial load and suppressing the emergence of resistance compared to monotherapy with either agent[1][3][5]. - **Clinical Need:** - Aimed at treating serious infections such as complicated urinary tract infections, intra-abdominal infections, and hospital-acquired pneumonia in the context of multidrug resistance, especially when limited treatment options are available[1][3][9][10].
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