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

NCT07478484 | Recruiting Phase 4

• 1 other identifier: 2026-SR-085
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ceftazidime-avibactam; Aztreonam; Gram-negative Bacterial Infection; Metallo-β-lactamase-producing; Carbapenem-resistant

Outcome Measures

Primary Outcomes (1)

• Clinical cure rate

  Clinical cure at Day 14 of treatment

  14 days

Study Arms (2)

concomitant infusion

EXPERIMENTAL

Drug: ceftazidime-avibactam combined with aztreonam

sequential infusion

ACTIVE COMPARATOR

Drug: ceftazidime-avibactam combined with aztreonam

Interventions

ceftazidime-avibactam combined with aztreonam DRUG

Ceftazidime-avibactam 2.5g every 8 hours (q8h) administered as a 3-hour concomitant intravenous infusion with aztreonam 2g q8h, versus ceftazidime-avibactam 2.5g q8h infused over 2 hours followed by a 1-hour intravenous infusion of aztreonam

concomitant infusion; sequential infusion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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;
• Patients receiving treatment with ceftazidime-avibactam in combination with aztreonam.

You may not qualify if:

• Patients aged under 18 years;
• 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);
• Pregnant or breastfeeding women;
• Patients unable to comprehend or comply with the study protocol;
• Any other condition which, in the investigator's discretion, makes the patient unsuitable for participation in the trial.

Sponsors & Collaborators

• Jing Zhou: lead

Study Sites (1)

Jing Zhou

Nanjin, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Interventions

Aztreonam

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 17, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

CN (1)