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

A Clinical Study on Sequential Infusion Versus Concomitant Infusion of Ceftazidime-avibactam Combined With Aztreonam for the Treatment of Metallo-β-lactamase-producing Carbapenem-resistant Gram-negative Bacterial Infections.

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.

Inclusion Criteria:

1. Patients diagnosed with complicated intra-abdominal infection (cIAI), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), or bloodstream infection (BSI);
2. Patients with confirmed infections caused by metallo-β-lactamase-producing carbapenem-resistant Gram-negative bacteria (MBL-CR-GNB), as determined by genotypic testing using next-generation sequencing (NGS) or carbapenem resistance gene testing;
3. Patients receiving treatment with ceftazidime-avibactam in combination with aztreonam.

Exclusion Criteria:

1. Patients aged under 18 years;
2. Patients with known hypersensitivity to ceftazidime, avibactam, aztreonam, or any of the excipients; or those with a history of severe hypersensitivity reactions (e.g., anaphylactic shock, severe skin reactions) to any other β-lactam antibacterial agents (such as penicillins, monobactams, or carbapenems);
3. Pregnant or breastfeeding women;
4. Patients unable to comprehend or comply with the study protocol;
5. Any other condition which, in the investigator's discretion, makes the patient unsuitable for participation in the trial.