Skip to content
1887

Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 73, Issue 7

New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant No Access

Abstract

Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ.

Sfx is more active against drug-resistant (Mtb) isolates.

To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb.

A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes.

Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC of 0.0313 µg ml and MIC of 0.125 µg ml, which was lower than that of Mfx (MIC = 0.0625 µg ml, MIC = 1 µg ml) and Lfx (MIC = 0.125 µg ml, MIC = 2 µg ml). We determined the tentative epidemiological cut-off values as 0.5 µg ml for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in or , 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident.

Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): fluoroquinolones , multidrug resistant , Mycobacterium tuberculosis and sitafloxacin
Funding
This study was supported by the:
  • Tongzhou Yunhe Project under Grant (Award YH201917)
    • Principle Award Recipient: QingSUN
  • Beijing Tongzhou Municipal Science & Technology commission (Award KJ2022CX044)
    • Principle Award Recipient: QingSUN
  • Beijing Public Health Experts Project (Award 2022-3-040)
    • Principle Award Recipient: QingSUN
© 2024 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001825
2024-07-19
2025-06-23
Loading full text...

Full text loading...

References

  1. World Health Organization Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment Geneva: World Health Organization; 2019
     [Google Scholar]
  2. World Health Organization Global Tuberculosis Report 2021 Geneva: World Health Organization; 2021
     [Google Scholar]
  3. Xia H, Zheng Y, Liu D, Wang S, He W et al. Strong increase in moxifloxacin resistance rate among multidrug-resistant Mycobacterium tuberculosis isolates in China, 2007 to 2013. Microbiol Spectr 2021; 9:e0040921 [View Article] [PubMed]
     [Google Scholar]
  4. Wang G, Jiang G, Jing W, Zong Z, Yu X et al. Prevalence and molecular characterizations of seven additional drug resistance among multidrug-resistant tuberculosis in China: a subsequent study of a national survey. J Infect 2021; 82:371–377 [View Article] [PubMed]
     [Google Scholar]
  5. Farhat MR, Mitnick CD, Franke MF, Kaur D, Sloutsky A et al. Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment. Int J Tuberc Lung Dis 2015; 19:339–341 [View Article] [PubMed]
     [Google Scholar]
  6. Miyashita N, Niki Y, Matsushima T. In vitro and in vivo activities of sitafloxacin against Chlamydia spp. Antimicrob Agents Chemother 2001; 45:3270–3272 [View Article] [PubMed]
     [Google Scholar]
  7. Dong X, Chen F, Zhang Y, Liu H, Liu Y et al. In vitro activities of sitafloxacin tested alone and in combination with rifampin, colistin, sulbactam, and tigecycline against extensively drug-resistant Acinetobacter baumannii. Int J Clin Exp Med 2015; 8:8135–8140 [PubMed]
     [Google Scholar]
  8. Sano C, Tatano Y, Shimizu T, Yamabe S, Sato K et al. Comparative in vitro and in vivo antimicrobial activities of sitafloxacin, gatifloxacin and moxifloxacin against Mycobacterium avium. Int J Antimicrob Agents 2011; 37:296–301 [View Article] [PubMed]
     [Google Scholar]
  9. Dhople AM, Namba K. In vitro activity of sitafloxacin (DU-6859a) alone, or in combination with rifampicin, against Mycobacterium ulcerans. J Antimicrob Chemother 2002; 50:727–729 [View Article] [PubMed]
     [Google Scholar]
  10. Murakami T, Aozasa N, Fukano H, Miyamoto Y, Ishii N et al. Successful treatment of cutaneous Mycobacterium chelonae infection by switching from levofloxacin to sitafloxacin. J Dermatol 2023; 50:e192–e193 [View Article] [PubMed]
     [Google Scholar]
  11. Takano K, Shimada D, Kashiwagura S, Kamioka Y, Hariu M et al. Severe pulmonary Mycobacterium abscessus cases due to co-infection with other microorganisms well treated by clarithromycin and sitafloxacin in Japan. Int Med Case Rep J 2021; 14:465–470 [View Article] [PubMed]
     [Google Scholar]
  12. Fujita K, Fujita M, Ito Y, Hirai T, Mio T et al. Preliminary evaluation of a sitafloxacin-containing regimen for relapsed or refractory pulmonary Mycobacterium avium complex disease. Open Forum Infect Dis 2016; 3:fw147 [View Article] [PubMed]
     [Google Scholar]
  13. Zhao Y, Xu S, Wang L, Chin DP, Wang S et al. National survey of drug-resistant tuberculosis in China. N Engl J Med 2012; 366:2161–2170 [View Article] [PubMed]
     [Google Scholar]
  14. Clinical and Laboratory Standards Institute Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia, and Other Aerobic Actinomycetes; Approved Standard, CLSI Document M62, 1st. edn Wayne, PA: 2018
     [Google Scholar]
  15. WHO Technical report on critical concentrations for TB drug susceptibility testing of medicines used in the treatment of drug-resistant TB Geneva, Switzerland: World Health Organization; 2018
     [Google Scholar]
  16. Tomioka H, Sato K, Shimizu T, Sano C. Anti-Mycobacterium tuberculosis activities of new fluoroquinolones in combination with other antituberculous drugs. J Infect 2002; 44:160–165 [View Article] [PubMed]
     [Google Scholar]
  17. Li R, Yu C, Li Y, Lam T-W, Yiu S-M et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 2009; 25:1966–1967 [View Article] [PubMed]
     [Google Scholar]
  18. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
     [Google Scholar]
  19. Yi L, Aono A, Chikamatsu K, Igarashi Y, Yamada H et al. In vitro activity of sitafloxacin against Mycobacterium tuberculosis with gyrA/B mutations isolated in Japan. J Med Microbiol 2017; 66:770–776 [View Article]
     [Google Scholar]
  20. Leechawengwongs M, Prammananan T, Jaitrong S, Billamas P, Makhao N et al. In vitro activity and MIC of sitafloxacin against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis isolated in Thailand. Antimicrob Agents Chemother 2018; 62:e00825-17 [View Article] [PubMed]
     [Google Scholar]
  21. Sun L-N, Sun G-X, Yang Y-Q, Shen Y, Huang F-R et al. Effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics of sitafloxacin granules in healthy subjects. Clin Pharmacol Drug Dev 2021; 10:57–67 [View Article] [PubMed]
     [Google Scholar]
  22. World Health Organization Technical report on the pharmacokinetics and pharmacodynamics (Pk/Pd) of medicines used in the treatment of drug-resistant tuberculosis 2018
     [Google Scholar]
  23. Maruri F, Sterling TR, Kaiga AW, Blackman A, van der Heijden YF et al. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system. J Antimicrob Chemother 2012; 67:819–831 [View Article] [PubMed]
     [Google Scholar]
  24. Maruri F, Guo Y, Blackman A, van der Heijden YF, Rebeiro PF et al. Resistance-conferring mutations on whole-genome sequencing of fluoroquinolone-resistant and -susceptible Mycobacterium tuberculosis isolates: a proposed threshold for identifying resistance. Clin Infect Dis 2021; 72:1910–1918 [View Article] [PubMed]
     [Google Scholar]
  25. Farhat MR, Jacobson KR, Franke MF, Kaur D, Sloutsky A et al. Gyrase mutations are associated with variable levels of fluoroquinolone resistance in Mycobacterium tuberculosis. J Clin Microbiol 2016; 54:727–733 [View Article] [PubMed]
     [Google Scholar]
  26. Suzuki Y, Nakajima C, Tamaru A, Kim H, Matsuba T et al. Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance. Int J Antimicrob Agents 2012; 39:435–439 [View Article] [PubMed]
     [Google Scholar]
  27. Rastogi N, Labrousse V, Goh KS. In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages. Curr Microbiol 1996; 33:167–175 [View Article] [PubMed]
     [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001825
Loading
New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant Mycobacterium tuberculosis
J. Med. Microbiol. 73, 001825 (2024); https://doi.org/10.1099/jmm.0.001825
/content/journal/jmm/10.1099/jmm.0.001825
/content/journal/jmm/10.1099/jmm.0.001825
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error