Institute of Global Health of Barcelona, Barcelona, Spain.
Department of Clinical Microbiology, Hospital Universitario Ramón y Cajal & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
PLoS One. 2019 Oct 9;14(10):e0223326. doi: 10.1371/journal.pone.0223326. eCollection 2019.
Ozenoxacin (OZN) belongs to a new generation of non-fluorinated quinolones for the topical treatment of skin infections which has shown to be effective in the treatment of susceptible and resistant Gram-positive cocci. The mutant prevention concentration (MPC) of ozenoxacin, levofloxacin and ciprofloxacin was determined in quinolone-susceptible and -resistant strains including methicillin-susceptible S. aureus, methicillin-resistant S. aureus, methicillin-susceptible S. epidermidis and methicillin-resistant S. epidermidis with different profile of mutation in the quinolone resistance determining regions (QRDR). The MPC value of OZN for the methicillin-susceptible S. aureus strain susceptible to quinolones, without mutations in QRDR, was 0.05 mg/L, being 280-fold lower than that observed with ciprofloxacin and levofloxacin. In methicillin-susceptible and-resistant S. aureus strains with mutations in the gyrA or/and grlA genes the MPC of OZN went from 0.1 to 6 mg/L, whereas the MPC of levofloxacin and ciprofloxacin was > 50 mg/L for the same strains. For methicillin-susceptible and-resistant S. epidermidis the results were similar to those abovementioned for S. aureus. According to our results, the MPC of OZN was far below the quantity of ozenoxacin achieved in the epidermal layer, suggesting that the in vivo selection of mutants, if it occurs, will take place at low frequency. Ozenoxacin is an excellent candidate for the treatment of bacterial infections caused by susceptible and quinolone-resistant staphylococci isolated usually from skin infections.
噁嗪酮(OZN)属于新一代非氟喹诺酮类药物,用于治疗皮肤感染,已被证明对治疗敏感和耐药革兰阳性球菌有效。在包括耐甲氧西林金黄色葡萄球菌、耐甲氧西林表皮葡萄球菌在内的对喹诺酮类敏感和耐药的菌株中,测定了噁嗪酮、左氧氟沙星和环丙沙星的突变预防浓度(MPC),这些菌株在喹诺酮耐药决定区(QRDR)中有不同的突变特征。对耐甲氧西林金黄色葡萄球菌敏感株(QRDR 无突变),噁嗪酮的 MPC 值为 0.05mg/L,比环丙沙星和左氧氟沙星低 280 倍。在 gyrA 或/和 grlA 基因突变的耐甲氧西林敏感和耐药金黄色葡萄球菌株中,噁嗪酮的 MPC 值为 0.1-6mg/L,而相同菌株的左氧氟沙星和环丙沙星的 MPC 值>50mg/L。对于耐甲氧西林敏感和耐药表皮葡萄球菌,结果与上述耐甲氧西林金黄色葡萄球菌相似。根据我们的结果,噁嗪酮的 MPC 远低于表皮层中噁嗪酮的含量,这表明如果发生突变体的体内选择,其发生的频率将很低。噁嗪酮是治疗由通常从皮肤感染中分离出的敏感和耐喹诺酮类葡萄球菌引起的细菌感染的理想候选药物。