Scholarlink

Objective <p>Evaluating the activity of six β-lactams in combination with different β-lactamase inhibitors to identify the most potent combination against <i>Mycobacterium</i> tuberculosis(MTB) in vitro.</p> Methods <p>A total of 105 MDR-TB strains from different regions of Henan province were included in this study.Drug susceptibility of sixβ-lactams alone or in combination with β-lactamase inhibitors was examined by broth dilution method against 105 clinical isolates.Mutations of <i>blaC</i>, <i>ldt</i><sub><i>mt1</i></sub>,<i>dacB2</i>and <i>ldt</i><sub><i>mt2</i></sub> were analyzed by PCR and DNA sequencing.</p> Results <p>Out of the β-lactams used herein, tebipenem was the most effective against MDR-TB and had an MIC<sub>90</sub> value of 16&#xa0;µg/ml.Clavulanic acid, tazobactam, and sulbactam, demonstrated the best synergy with tebipenem, resultingin an 32-fold reduction in theMIC values for 12, 5, and 20 strains, respectively. Simultaneously, these three types ofβ-lactamase inhibitors had the least impact on imipenem.Clavulanic acid caused the maximum 8-fold reduction in the MIC value of imipenem, while tazobactam and sulbactam only resulted in the maximum 4-fold reduction in the MIC value of imipenem. Besides, after the addition ofβ-lactamase inhibitors, the MICs of most β-lactam drugs were reduced more evidently in the presence of avibactamand tazobactamcompared to other β-lactamase inhibitors. In addition, 13.33% (14/105) of isolates harbored mutations in the blaC gene, with three different nucleotide substitutions: AGT333AGG 、AAC638ACCand ATC786ATT. For the strains with a Ser111Arg andAsn213Thrsubstitution inBlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the meropenem-sulbactam combinationsthan that in a synonymous single nucleotide polymorphism (SNP) group.</p> Conclusion <p>the combination of tebipenem and relebactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg and Asn213Thr substitution of BlaC may be associated with increased susceptibility of MDR-TB isolates to meropenem in thepresence of clavulanate and sulbactam.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月28日

查看全文
  • Jie Shi,
  • Danwei Zheng,
  • Ruyue Su,
  • Xiaoguang Ma,
  • Yankun Zhu,
  • Shaohua Wang,
  • Wenjing Chang,
  • Dingyong Sun

摘要

Objective

Evaluating the activity of six β-lactams in combination with different β-lactamase inhibitors to identify the most potent combination against Mycobacterium tuberculosis(MTB) in vitro.

Methods

A total of 105 MDR-TB strains from different regions of Henan province were included in this study.Drug susceptibility of sixβ-lactams alone or in combination with β-lactamase inhibitors was examined by broth dilution method against 105 clinical isolates.Mutations of blaC, ldtmt1,dacB2and ldtmt2 were analyzed by PCR and DNA sequencing.

Results

Out of the β-lactams used herein, tebipenem was the most effective against MDR-TB and had an MIC90 value of 16 µg/ml.Clavulanic acid, tazobactam, and sulbactam, demonstrated the best synergy with tebipenem, resultingin an 32-fold reduction in theMIC values for 12, 5, and 20 strains, respectively. Simultaneously, these three types ofβ-lactamase inhibitors had the least impact on imipenem.Clavulanic acid caused the maximum 8-fold reduction in the MIC value of imipenem, while tazobactam and sulbactam only resulted in the maximum 4-fold reduction in the MIC value of imipenem. Besides, after the addition ofβ-lactamase inhibitors, the MICs of most β-lactam drugs were reduced more evidently in the presence of avibactamand tazobactamcompared to other β-lactamase inhibitors. In addition, 13.33% (14/105) of isolates harbored mutations in the blaC gene, with three different nucleotide substitutions: AGT333AGG 、AAC638ACCand ATC786ATT. For the strains with a Ser111Arg andAsn213Thrsubstitution inBlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the meropenem-sulbactam combinationsthan that in a synonymous single nucleotide polymorphism (SNP) group.

Conclusion

the combination of tebipenem and relebactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg and Asn213Thr substitution of BlaC may be associated with increased susceptibility of MDR-TB isolates to meropenem in thepresence of clavulanate and sulbactam.