@article{mbs:/content/journal/jmm/10.1099/jmm.0.000493, author = "Yi, Lina and Aono, Akio and Chikamatsu, Kinuyo and Igarashi, Yuriko and Yamada, Hiroyuki and Takaki, Akiko and Mitarai, Satoshi", title = "In vitro activity of sitafloxacin against Mycobacterium tuberculosis with gyrA/B mutations isolated in Japan", journal= "Journal of Medical Microbiology", year = "2017", volume = "66", number = "6", pages = "770-776", doi = "https://doi.org/10.1099/jmm.0.000493", url = "https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000493", publisher = "Microbiology Society", issn = "1473-5644", type = "Journal Article", keywords = "minimum inhibitory concentrations", keywords = "epidemiological cut-off value", keywords = "gyrase B gene", keywords = "sitafloxacin", keywords = "gyrase A gene", abstract = " Purpose. Sitafloxacin (SFX) is a new fluoroquinolone (FQ) that has shown a strong bactericidal effect against Mycobacterium tuberculosis (Mtb) in vitro. However, data on SFX efficacy against Mtb with gyrA/B mutations and its epidemiological cut-off (ECOFF) value remain limited. Therefore, we evaluated and compared the in vitro activity of SFX against gyrA/B-mutant Mtb to that of moxifloxacin (MFX), levofloxacin (LFX) and ciprofloxacin (CFX), and determined the ECOFF for SFX. Methodology. A total of 109 clinical Mtb isolates, including 73 multidrug-resistant (MDR) isolates, were subjected to minimum inhibitory concentration (MIC) analysis in oleic-albumin-dextrose-catalase (OADC)-supplemented Middlebrook 7H9 medium. Our results showed that SFX had lower cumulative MIC than MFX, LFX and CFX. Furthermore, we performed direct DNA sequencing of the quinolone-resistance-determining regions (QRDRs). Results. We identified the following mutations: D94G, D94A, A90V, D94H, D94N and G88A in gyrA; and A543V, A543T, E540D, R485C, D500A, I552S and D577A in gyrB. Based on our results, an ECOFF of 0.125 µg ml−1 was proposed for SFX. With this ECOFF, 15 % of LFX-resistant isolates with MIC ≥2 µg ml−1 were susceptible to SFX. Conclusion. SFX had the lowest cumulative MIC and a relatively low ECOFF value against Mtb, indicating that SFX was not only more effective against gyrA-mutant isolates, but also MDR isolates in Japan.", }