BACKGROUND & AIMS:
: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.
背景与目标:
: 目的。西他沙星 (SFX) 是一种新型氟喹诺酮 (FQ),在体外对结核分枝杆菌 (Mtb) 具有很强的杀菌作用。然而,关于SFX对具有gyrA/B突变的Mtb的疗效及其流行病学临界值 (ECOFF) 的数据仍然有限。因此,我们评估并比较了SFX对gyrA/B-突变体Mtb的体外活性与莫西沙星 (MFX),左氧氟沙星 (LFX) 和环丙沙星 (CFX) 的体外活性,并确定了SFX的eoff方法学。在添加了油酸-白蛋白-葡萄糖-过氧化氢酶 (OADC) 的Middlebrook 7H9培养基中,对总共109个临床Mtb分离株 (包括73个多药耐药 (MDR) 分离株) 进行了最低抑菌浓度 (MIC) 分析。我们的结果表明,SFX的累积MIC低于MFX,LFX和CFX。此外,我们对喹诺酮类耐药决定区 (qrdr) 进行了直接DNA测序。我们鉴定了以下突变: gyrA中的D94G,D94A,A90V,D94H,D94N和G88A; gyrB中的A543V,A543T,E540D,R485C,D500A,I552S和D577A。根据我们的结果,提出了一种用于SFX的0.125 µ g ml-1。在这种情况下,15 % 的抗LFX的MIC ≥ 2 µ g ml-1菌株对SFX敏感。结论。SFX的累积MIC最低,对Mtb的eoff值相对较低,表明SFX不仅对gyrA突变分离株更有效,而且在日本对MDR分离株也更有效。