建立头孢吡肟-他尼波巴坦标准肉汤微量稀释MIC法。

IF 5.4 2区 医学 Q1 MICROBIOLOGY
Journal of Clinical Microbiology Pub Date : 2025-09-10 Epub Date: 2025-08-19 DOI:10.1128/jcm.00661-25
Adam Belley, Susan M Cusick, Dan C Pevear, Laura Koeth, Jeanna DiFranco-Fisher, Nimmi Kothari, Stephen Hawser, Greg Moeck
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引用次数: 0

摘要

正在研究的β-内酰胺/β-内酰胺酶抑制剂联合头孢吡肟-taniborbactam用于治疗对第三代头孢菌素和碳青霉烯类耐药的革兰氏阴性病原体引起的严重感染。建立符合临床实验室标准协会(CLSI) M07和国际标准组织20776-1:2019标准的头孢吡肟-他尼波巴坦药敏试验参考方法对于告知患者护理是必要的。本研究建立了头孢吡肟-taniborbactam (taniborbactam固定浓度为4µg/mL)的参比肉汤微量稀释MIC法。在CLSI M23二级研究中,包括9个临床微生物实验室,ctx - m -15生产者大肠杆菌NCTCC 13353被确定为适合常规质量控制(QC),因为头孢吡肟(≥64µg/mL)和头孢吡肟-坦尼波巴坦(0.12至1µg/mL)的范围不重叠,从而同时控制头孢吡肟的抗菌活性和坦尼波巴坦β-内酰胺酶抑制。在获得的头孢吡肟-他尼波巴坦MIC结果中,99.6%(269/270)在确定的QC范围内;同样,来自一项监测研究和sure -1 iii期临床研究(clintrials.gov标识符NCT03840148)的两个中心微生物实验室的QC值分别为100%(79/79)和98.0%(98/100)在范围内。对标准培养基(pH值、阳离子含量或添加人血清、白蛋白、聚山酸酯-80或肺表面活性剂)或测定参数(接种量密度、培养时间和气氛)的修改显示,只有接种滴度(例如,≥5 × 106 CFU/mL)超过CLSI M07标准(2-8 × 105 CFU/mL), MIC值才会高于QC范围。结果表明,头孢吡肟-他尼波巴坦肉汤微量稀释MIC参比法在符合批准标准的情况下具有稳健性和可靠性。重要性:这项研究的重点是一种名为头孢吡肟-塔尼波巴坦的新型抗生素组合,该组合正在开发中,用于治疗由细菌引起的严重感染,这些细菌通常对目前的治疗具有耐药性。为了确保这种新的抗生素组合一旦被批准用于临床,就能安全有效地使用,我们开发了一种标准化的实验室方法来测量其对某些细菌的活性,这些细菌在质量控制测试中被广泛使用。该方法在多个实验室进行了评估,证明该方法可靠、准确、一致。它在不同的测试条件下也表现良好,表明它是指导治疗决策的可靠工具。这是应对抗生素耐药感染挑战的重要一步,因为它将帮助临床医生评估头孢吡肟-坦尼波巴坦作为一种潜在的治疗选择,因为他们正在努力改善严重感染患者的护理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Establishing the reference broth microdilution MIC method for cefepime-taniborbactam.

The investigational β-lactam/β-lactamase inhibitor combination cefepime-taniborbactam is intended as therapy for serious infections caused by Gram-negative pathogens resistant to third-generation cephalosporins and carbapenems. Establishing a susceptibility testing reference method for cefepime-taniborbactam that conforms to the Clinical Laboratory Standards Institute (CLSI) M07 and International Standards Organization 20776-1:2019 standards is necessary to inform patient care. This study describes the reference broth microdilution MIC method for cefepime-taniborbactam (taniborbactam fixed at 4 µg/mL). In a CLSI M23 Tier 2 study that included nine clinical microbiology laboratories, the CTX-M-15-producer Escherichia coli NCTCC 13353 was determined to be appropriate for routine quality control (QC) as ranges for cefepime (≥64 µg/mL) and cefepime-taniborbactam (0.12 to 1 µg/mL) were non-overlapping, thereby simultaneously controlling for cefepime antibacterial activity and taniborbactam β-lactamase inhibition. Of the cefepime-taniborbactam MIC results obtained, 99.6% (269/270) were within the identified QC range; similarly, 100% (79/79) and 98.0% (98/100) of the QC values from a surveillance study and from the two central microbiology laboratories of the CERTAIN-1 Phase 3 clinical study (clintrials.gov identifier NCT03840148) were in range, respectively. Modifications to the standard medium (pH, cation content, or supplementation with human serum, albumin, polysorbate-80, or pulmonary surfactant) or assay parameters (inoculum density, incubation duration, and atmosphere) revealed that only inoculum titers (e.g., ≥5 × 106 CFU/mL) exceeding the CLSI M07 standard (2-8 × 105 CFU/mL) increased MIC values above the QC range. These results demonstrate the robustness and reliability of the cefepime-taniborbactam broth microdilution MIC reference method when performed following the approved standards.

Importance: This study focuses on a new antibiotic combination called cefepime-taniborbactam that is being developed to treat serious infections caused by bacteria that are often resistant to current treatments. To make sure this new antibiotic combination can be used safely and effectively once it has been approved for clinical use, we developed a standardized laboratory method to measure its activity against certain bacteria that are widely used during quality control testing. The method was assessed in multiple labs and proved to be reliable, accurate, and consistent. It also held up well under different testing conditions, showing that it is a dependable tool for guiding treatment decisions. This is an important step in meeting the challenge of antibiotic-resistant infections since it will help clinicians evaluate cefepime-taniborbactam as a potential treatment option as they strive to improve the care of patients suffering from serious infections.

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来源期刊
Journal of Clinical Microbiology
Journal of Clinical Microbiology 医学-微生物学
CiteScore
17.10
自引率
4.30%
发文量
347
审稿时长
3 months
期刊介绍: The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.
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