In vitroactivity of sitafloxacin againstMycobacterium tuberculosiswithgyrA/Bmutations isolated in Japan. Issue 6 (June 2017) - Yi, Lina
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.