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Monitoring the concentration of antibiotics rapidly and cost-effectively is crucial for accurate clinical medication and timely identification of drug-induced illnesses. Here, we constructed a novel fluorescent assay kit to monitor Zavicefta, an effective antibiotic composed of avibactam (AVI) and ceftazidime (CFZ) to treat carbapenem-resistant gram-negative bacteria infections. AVI can emit fluorescence, but CFZ cannot. To enable simultaneous measurement of both in one kit, we designed molecularly imprinted polymer (MIP) modified quantum dots (QDs) for CFZ determination. MIPs have received significant attention as an artificial antibody due to their exceptional specificity for various targets, particularly drugs with small molecular weight. Under the excitation wavelength of 350 nm, the detection process involves a decrease in QDs' fluorescence signal at 600 nm owing to the "gate effect" between MIP and CFZ and the internal filtration effect between CFZ and QDs. Simultaneously, a fluorescence emission characteristic peak at 420 nm for AVI emerges. In addition, to simplify the operation procedure and improve determination throughput, the detection agents were incorporated into a hydrogel and placed in a 96-well plate, enabling concurrent quantification of AVI and CFZ within the respective range of 80-1000 μM and 1-1000 μM. The developed assay kit successfully determined AVI and CFZ in human serums and therapeutic drug monitoring in a live rabbit model. Recoveries of AVI and CFZ were 92.7-114%, with relative standard deviations below 6.0%. Moreover, a smartphone was employed to read the fluorescence signals, which was beneficial for cost reduction and out-of-lab analysis. This study will deliver a pragmatic resolution to developing high-throughput assay kits for drug determination., (© 2024. The Author(s).)

Objectives: The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing., Methods: Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing., Results: Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition., Conclusions: In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)