Ceftazidime-avibactam for the treatment of infections caused by carbapenem-resistant Gram-negative pathogens in Chinese patients: A phase IV, multi-center, open‑label study.

BACKGROUND

Ceftazidime-avibactam is approved in China for complicated intra‑abdominal infections (cIAIs), hospital-acquired/ventilator-associated pneumonia (HAP/VAP), and other infections with limited treatment options due to aerobic Gram‑negative bacteria. This post-approval phase IV study assessed the effectiveness and safety of ceftazidime-avibactam in Chinese adults with carbapenem-resistant Gram-negative bacterial infections.

METHODS

In this prospective, multi-center, open-label, active-controlled study in China, patients with bloodstream infections, cIAIs, complicated urinary tract infections, and HAP/VAP were randomized to ceftazidime-avibactam or best available treatment (BAT). The primary efficacy endpoint was clinical response at the test-of-cure (TOC) visit in the microbiologically modified intention-to-treat (mMITT) analysis set. Endpoint comparisons were descriptive with nominal P-values.

RESULTS

Overall, 59 patients received ceftazidime-avibactam (n=30) or BAT (n=29), mostly for primary HAP/VAP (>70%, both arms). The most common baseline isolate was Klebsiella pneumoniae (ceftazidime-avibactam, 66.7% [16/24]; BAT, 84.6% [22/26]). In the mMITT set (n=27, each arm), clinical cure (95% confidence interval) at TOC was higher for ceftazidime-avibactam (59.3% [40.6-76.1]) than BAT (25.9% [12.4-44.3]). Microbiological response at TOC favored ceftazidime‑avibactam (59.3%) over BAT (25.9%). All-cause mortality at day 28 was similar for ceftazidime-avibactam (4/30 [13.3%]) and BAT (4/29 [13.8%]; intention‑to‑treat analysis set). Adverse events (AEs) in patients treated with ceftazidime‑avibactam versus BAT included: all-causality AEs, 24 (80.0%) vs. 26 (89.7%); serious AEs, 7 (23.3%) vs. 11 (37.9%); severe AEs, 6 (20.0%) vs. 11 (37.9%); and AEs leading to death, 5 (16.7%) vs. 7 (24.1%).

CONCLUSIONS

These results support the effectiveness and safety of ceftazidime‑avibactam in Chinese patients with carbapenem-resistant infections and limited treatment options.

GOV IDENTIFIER: NCT04882085.