activity of sitafloxacin against with mutations isolated in Japan.

Sitafloxacin (SFX) is a new fluoroquinolone (FQ) that has shown a strong bactericidal effect against (Mtb) . However, data on SFX efficacy against Mtb with mutations and its epidemiological cut-off (ECOFF) value remain limited. Therefore, we evaluated and compared the activity of SFX against -mutant Mtb to that of moxifloxacin (MFX), levofloxacin (LFX) and ciprofloxacin (CFX), and determined the ECOFF for SFX. 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). We identified the following mutations: D94G, D94A, A90V, D94H, D94N and G88A in gyrA; and A543V, A543T, E540D, R485C, D500A, I552S and D577A in . Based on our results, an ECOFF of 0.125 µg ml was proposed for SFX. With this ECOFF, 15 % of LFX-resistant isolates with MIC ≥2 µg ml were susceptible to SFX. SFX had the lowest cumulative MIC and a relatively low ECOFF value against Mtb, indicating that SFX was not only more effective against -mutant isolates, but also MDR isolates in Japan.