In Vitro Activity of Cefaclor/Beta-Lactamases Inhibitors (Clavulanic Acid and Sulbactam) Combination Against Extended-Spectrum Beta-Lactamase Producing Uropathogenic E. coli.

IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES
Ali Atoom, Bayan Alzubi, Dana Barakat, Rana Abu-Gheyab, Dalia Ismail-Agha, Awatef Al-Kaabneh, Nawfal Numan
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引用次数: 0

Abstract

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL-BLI combinations against ESBL-producing E. coli isolated from urinary tract infections (UTIs). Objective: This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing E. coli isolates derived from urine cultures of patients diagnosed with UTIs. Methods: The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. Results: The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time-kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. Conclusions: This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial.

头孢克洛/ β -内酰胺酶抑制剂(克拉维酸和舒巴坦)联合对广谱β -内酰胺酶产尿路致病性大肠杆菌的体外活性研究
背景:由多药耐药(MDR)表型引起的尿路感染(UTIs)被称为广谱β -内酰胺酶(ESBL)产生大肠杆菌,是一个重要的和日益增长的全球健康问题。为了应对不断上升的发病率,近年来引入了新型β -内酰胺酶抑制剂(BL/BLI)组合。虽然这些药物已经显示出疗效,但它们的临床应用受到高成本、有限可用性和新出现的耐药机制的限制。本研究的目的是测试一种具有成本效益的替代目前可用的BL-BLI组合的体外活性,以对抗从尿路感染(uti)中分离出来的产esbl的大肠杆菌。目的:研究头孢克洛(CFC)单用和联用β-内酰胺酶抑制剂克拉维酸(CA)和舒巴坦(SUL)对52株产esbl大肠杆菌的体外抑菌活性,这些大肠杆菌来源于诊断为uti的患者尿液培养物。方法:采用纸片扩散法和最小抑菌浓度法测定药敏范围。此外,采用时间杀伤法和圆盘近似法测定了接近组合的增效和杀菌活性。结果:CFC与CA或SUL联合使用时,CFC的MIC50和MIC90均由大于128µg/mL提高到8/4µg/mL。CFC/CA/SUL三联剂型MIC50和MIC90值分别为8/4/4µg/mL和64/32/32µg/mL。CFC/CA、CFC/SUL和CFC/CA/SUL组合的恢复敏感性分别为54%、54%和58%。圆盘近似和时间杀伤试验结果显示,当CFC与CA或SUL结合时,对分离物具有协同作用和杀菌作用,当通过圆盘扩散和MIC方法与CA或SUL结合时,CFC表现出敏感性恢复。结论:本研究提出了一种具有成本效益的组合,可以减轻耐药性的发展,并为包括碳青霉烯类药物在内的最后治疗选择提供节省的选择。然而,在临床环境中测试疗效是至关重要的。
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来源期刊
Antibiotics-Basel
Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍: Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.
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