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Heliyon

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Comparison of the in vitro antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against Mycobacterium tuberculosis strains isolated in China

Published:30 October 2023 DOI: 10.1016/j.heliyon.2023.e21216 PMID: 37954372
Yaoyao Kong,?Zhi Geng,?Guanglu Jiang,?Junnan Jia,?Fen Wang,?Xiaoyi Jiang,?Yuzhen Gu,?Zhenyan Qi,?Naihui Chu,?Hairong Huang,?Xia Yu

Abstract

Objective: The resistance of Mycobacterium tuberculosis (Mtb) to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of Mtb to next-generation FQs in vitro and determine the correlation of FQs resistance and newly detected mutations in gyrB by molecular docking.

Methods: Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.e., sitafloxacin (SFX), finafloxacin (FIN) and delafloxacin (DFX) against Mtb clinical isolates obtained in 2015 and 2022, respectively. Quinolone-resistance-determining regions of gyrA and gyrB were subjected to DNA sequencing and the correlation of FQs resistance and new mutations in gyrB were determined by molecular docking. Furthermore, the intracellular antibacterial activity of the six FQs against Mtb H37Rv in THP-1?cells was evaluated.

Results: SFX exhibited the highest antibacterial activity against Mtb isolates (MIC90?=?0.25?μg/mL), whereas DFX and OFX exhibited comparable activity (MIC90?=?8?μg/mL). A statistically significant difference was observed among the MICs of the new generation FQs (SFX, P?=?0.002; DFX, P?=?0.008). Additionally, a marked increase in MICs was found in strains isolated in 2022 compared with those isolated in 2015. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A. Cross-resistance rate between SFX and MFX was 40.6?% (26/64). At a concentration of 1?μg/mL, SFX exhibited high intracellular antibacterial activity (96.6?%?±?1.5?%) against the Mtb H37Rv, comparable with that of MFX at a concentration of 2?μg/mL.

Conclusion: SFX exhibits the highest inhibitory activity against Mtb in vitro and THP-1?cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of Mtb infections.

Substances (34)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Levofloxacin 100986-85-4 C18H20FN3O4 765 suppliers $5.00-$1504.50
Levofloxacin 100986-85-4 C18H20FN3O4 765 suppliers $5.00-$1504.50
Levofloxacin 100986-85-4 C18H20FN3O4 765 suppliers $5.00-$1504.50
Levofloxacin 100986-85-4 C18H20FN3O4 765 suppliers $5.00-$1504.50
Ofloxacin 82419-36-1 C18H20FN3O4 633 suppliers $5.00-$2000.00
Ofloxacin 82419-36-1 C18H20FN3O4 633 suppliers $5.00-$2000.00
Ofloxacin 82419-36-1 C18H20FN3O4 633 suppliers $5.00-$2000.00
Ofloxacin 82419-36-1 C18H20FN3O4 633 suppliers $5.00-$2000.00
Moxifloxacin 151096-09-2 C21H24FN3O4 359 suppliers $13.00-$2487.00
Moxifloxacin 151096-09-2 C21H24FN3O4 359 suppliers $13.00-$2487.00

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