Clinical Research Directory

Individualized Precision Therapy With Ceftazidime and Avibactam Guided by PK/PD in Geriatric Populations

Ceftazidime-avibactam is a β-lactam/β-lactamase inhibitor combination treatment which has been developed to address infections caused by ESBL-, AmpC- and serine carbapenemase-producing Gram-negative bacteria. In elderly patients, significant interindividual variability often leads to inappropriate dosing (subtherapeutic or excessive), compromising efficacy or increasing toxicity risks. This prospective, multicenter study will enroll patients aged ≥60 years receiving ceftobiprole. Using LC-MS/MS for therapeutic drug monitoring (TDM), we will measure plasma concentrations and integrate individual characteristics (age, body weight, creatinine clearance, etc.). Population pharmacokinetic (PPK) modeling with Bayesian forecasting will be employed to estimate individual PK parameters and identify covariates influencing variability, thereby establishing a PPK model for ceftazidime-avibactam in the elderly. Based on pathogen-specific MIC values, dosing regimens (dose, frequency) will be dynamically optimized to guide precision therapy. Subsequent TDM data will continuously refine the PPK model, creating a self-optimizing system. This framework lays the groundwork for extending individualized treatment strategies to other antimicrobials in geriatric populations.

Different Administration Regimens of CAZ-AVI in Combination With ATM for the Treatment of CR-GNB

Metallo-β-lactamase-producing carbapenem-resistant Gram-negative bacteria (MBL-CR-GNB), due to their capacity to hydrolyze almost all β-lactam antibiotics, have become a critical global threat in antimicrobial resistance. Current novel β-lactamase inhibitors (e.g., avibactam, relebactam, vaborbactam) only inhibit serine enzymes and are ineffective against metallo-β-lactamases (MBL), severely limiting clinical treatment options. Aztreonam (ATM) is inherently stable against MBL, while avibactam (AVI) inhibits co-produced serine β-lactamases (e.g., KPC, OXA-48). Their combination achieves complementary synergistic antibacterial effects. The ceftazidime-avibactam plus aztreonam (CZA+ATM) regimen, operating via the mechanism of "avibactam protecting aztreonam", has demonstrated synergistic bactericidal activity against NDM, VIM, IMP and other MBL-producers in multiple real-world and clinical studies, significantly reducing infection-related mortality.However, although current domestic and international guidelines recommend the CZA+ATM combination for MBL infections, there is no consensus on optimal infusion strategies. Based on the above, this study hypothesizes that in patients with complicated infections caused by MBL-producing CR-GNB, different infusion modalities of ceftazidime-avibactam combined with aztreonam-concomitant infusion versus sequential infusion-will show no significant differences in PK/PD target attainment rates, clinical cure rates, microbiological eradication rates, or all-cause mortality, without increasing the risk of adverse events.