Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro
Abstract 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 t...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12879-025-10730-y |
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| author | Jie Shi Danwei Zheng Ruyue Su Xiaoguang Ma Yankun Zhu Shaohua Wang Wenjing Chang Dingyong Sun |
| author_facet | Jie Shi Danwei Zheng Ruyue Su Xiaoguang Ma Yankun Zhu Shaohua Wang Wenjing Chang Dingyong Sun |
| author_sort | Jie Shi |
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| description | Abstract 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, ldt mt1 ,dacB2and ldt mt2 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. |
| format | Article |
| id | doaj-art-272d3e6d4a8e46d2967977090b9095ca |
| institution | DOAJ |
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| publishDate | 2025-04-01 |
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| series | BMC Infectious Diseases |
| spelling | doaj-art-272d3e6d4a8e46d2967977090b9095ca2025-08-20T02:55:21ZengBMCBMC Infectious Diseases1471-23342025-04-0125111310.1186/s12879-025-10730-yComparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitroJie Shi0Danwei Zheng1Ruyue Su2Xiaoguang Ma3Yankun Zhu4Shaohua Wang5Wenjing Chang6Dingyong Sun7Henan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionHenan Province Center for Disease Control and PreventionAbstract 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, ldt mt1 ,dacB2and ldt mt2 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.https://doi.org/10.1186/s12879-025-10730-yβ-Lactamase inhibitorsAvibanvctamRelebactamβ-LactamsMultidrug-Resistant Mycobacterium tuberculosis |
| spellingShingle | Jie Shi Danwei Zheng Ruyue Su Xiaoguang Ma Yankun Zhu Shaohua Wang Wenjing Chang Dingyong Sun Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro BMC Infectious Diseases β-Lactamase inhibitors Avibanvctam Relebactam β-Lactams Multidrug-Resistant Mycobacterium tuberculosis |
| title | Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro |
| title_full | Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro |
| title_fullStr | Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro |
| title_full_unstemmed | Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro |
| title_short | Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro |
| title_sort | comparative evaluation of five β lactamase inhibitors in combination with β lactams against multidrug resistant mycobacterium tuberculosis in vitro |
| topic | β-Lactamase inhibitors Avibanvctam Relebactam β-Lactams Multidrug-Resistant Mycobacterium tuberculosis |
| url | https://doi.org/10.1186/s12879-025-10730-y |
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