Study on the Antibacterial Efficacy of Ceftazidime‐Avibactam Combined With Aztreonam against Multidrug‐Resistant Bacteria in Hypothermic Organ Preservation Solution

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BACKGROUND: The use of antimicrobial agents in the preservation solution (PS) could prevent the bacterial transmission to recipients in organ transplantation. However, antibiotics may exhibit different decontamination efficacy in the hypothermic PS. This study aimed to evaluate the antibacterial activity of ceftazidime-avibactam (CAZ-AVI) combined with aztreonam (ATM) against multidrug-resistant bacteria (MDRB) at varying ratios and concentrations during 3 h, 0°C-4°C PS decontamination. METHODS: An in vitro model simulating PS decontamination was established. Five MDRB isolates were collected and tested (CRKP, CRPA, CREC, CRAB, and MRSA). CAZ-AVI and ATM were prepared at different ratios (1:1, 1:2, 1:4, 2:1) and concentration gradients (0.5×, 1×, 2×, 4× the baseline). Antibacterial efficacy was recorded and analyzed. RESULTS: For CRKP and CREC, the 2:1 ratio at 0.5× concentration (250 mg/L CAZ-AVI + 0.5 g/L ATM) showed significant antibacterial effects (p = 0.002 and p < 0.001, respectively). For CRPA, efficacy was observed at the 1× concentration with a 2:1 ratio (500 mg/L CAZ-AVI + 1.0 g/L ATM; p = 0.022), while for CRAB, the 1:1 ratio at 0.5× concentration (125 mg/L CAZ-AVI + 0.5 g/L ATM; p < 0.001) was effective. The combination was only effective against MRSA at high concentrations (1000 mg/L CAZ-AVI + 2.0 g/L ATM; p < 0.001). CONCLUSIONS: The combination of CAZ-AVI and ATM effectively decontaminates MDR Gram-negative bacteria in PS. The 2:1 ratio at baseline concentration is recommended for clinical use, with potential escalation of CAZ-AVI concentration if needed.

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