Sitafloxacin Hydrate

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.

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.

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.

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.

Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A ¹³C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.