Antibiotics-Basel
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2025
·Vol. 14
·期 9
·915
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IF 4.6
Ru Wang,Kun Mi,Aihua Lu,Chengyang Zhang,Lei Sun,Yuxiang Chen,Yuanhu Pan,Yanfei Tao,Lingli Huang
Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producingEscherichia coliposes a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) and sulbactam have been coadministered in the clinical settings; however, discrepancies in their pharmacokinetics raise concerns regarding the rationality of this combination.Methods: This study was designed to investigate the postβ-lactamase inhibitor effect (PLIE) under both static and dynamic conditions, with the aim of supporting the clinical application of this combination.Results: The minimum inhibitory concentration (MIC) of CRO/SBT (2:1 ratio) againstE. coliNCTC 13353 was determined to be 32/16 μg/mL. The PLIEs were determined to be −1.26, −0.57, and 0.37 h at CRO/SBT concentrations ranging from 1/2 MIC to 2 MIC, respectively. The results of CRO concentration, β-lactamase activity,blaCTX-M-15expression, and cell morphology collectively support that SBT exerts PLIEs and protects against the antibacterial activity of CRO. In the dynamic hollow-fiber infection model, CRO monotherapy showed no inhibitory effect onE. coli, whereas CRO/SBT combination therapy rapidly eliminated SBT, achieved comparable bactericidal effects, prolonged CRO exposure, and maintained low β-lactamase activity levels.Conclusions: In conclusion, CRO/SBT exerts an inhibitory effect on enzyme-producing strains by being able to produce PLIE to maintain the inhibition of β-lactamase.
研究领域:
微生物学
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感染病学
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药理学
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临床药学
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抗菌药物治疗
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Rongrong Xuan,Bingye Shi,Dongchen Li,Yihui Chen,Chunyan Hou,Rufeng Jiang,Mengyue Guo,Yongyan Zhang,Tingting Wang
In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic β-lactam antibiotics and β-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g −1 . The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 − 0.2 ng mL −1 . In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3–105.4 % for intra-day and 90.6–103.5 % for inter-day, with low relative standard deviations of 1.3–7.2 % and 4.9–10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.
研究领域:
分析化学
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药物分析
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纳米技术
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材料科学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2020
·
IF 3.232
Pan Yu,Jia-Ning Yang,Jin-Wu Yan,Zhi-Zhong Meng,W. David Hong,Adam P. Roberts,Stephen A. Ward,Lei Zhang,Shan Li
The rapid detection of β-lactamases (Blas) and effective screening of Bla inhibitors are critically important and urgent for solving antibiotic resistance and improving precision medicine. Here a novel fluorescent probe CDC-559 was designed and synthesized, which can be used for the selective and direct detection of AmpC Blas. More importantly, it can realize screening the Bla inhibitors with sulbactam sodium and tazobactam as model compounds, and the half-maximal inhibitory concentration are 0.279 μM and 0.053 μM, respectively. CDC-559 can be applied not only to examine the resistance of bacterial strains, but also to categorize its mode of action specifically, which is consistent with the essential result of the Blas. The research suggests that CDC-559 probe has tremendous potential in the rapid detection of AmpC Blas as well as the strains with AmpC-encoded gene, which is instructive in promoting better antibiotic stewardship practices and developments.
研究领域:
化学
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药理学
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微生物学
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生物医学工程
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DOI
PubMed
高影响因子
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