In vitro activity of β-lactamase inhibitors combined with different β-lac-tam antibiotics against multidrug-resistant Mycobacterium tuberculosis clinical strains
10.12138/j.issn.1671-9638.20245121
- VernacularTitle:β-内酰胺酶抑制剂联合不同β-内酰胺类抗生素对耐多药结核分枝杆菌临床菌株体外活性研究
- Author:
Jie SHI
1
;
Dan-Wei ZHENG
;
Ji-Ying XU
;
Xiao-Guang MA
;
Ru-Yue SU
;
Yan-Kun ZHU
;
Shao-Hua WANG
;
Wen-Jing CHANG
;
Ding-Yong SUN
Author Information
1. 河南省疾病预防控制中心结核病防治所结核病参比实验室,河南郑州 450016
- Keywords:
Mycobacterium tuberculosis;
β-lactam;
β-lactamase inhibitor;
multidrug-resistant Mycobacterium tu-berculosis
- From:
Chinese Journal of Infection Control
2024;23(9):1091-1097
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.
