Melinta Therapeutics, New Haven, Connecticut, USA
Melinta Therapeutics, New Haven, Connecticut, USA.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00772-17. Print 2017 Sep.
Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685 isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints. isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC values against levofloxacin-nonsusceptible , methicillin-resistant (MRSA), and methicillin-susceptible isolates were all 0.25 μg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR). was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with isolates with the S84L mutation in and the S80Y mutation in , the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.).
德拉沙星是一种研究中的阴离子氟喹诺酮类抗生素，具有广谱活性，包括对革兰氏阳性菌、革兰氏阴性菌、非典型菌和厌氧菌的活性。在两项全球 3 期研究中，比较了德拉沙星与万古霉素加氨曲南治疗急性细菌性皮肤和皮肤结构感染（ABSSSI）患者，评估了对氟喹诺酮类敏感和耐药分离株的德拉沙星活性和微生物学反应百分比。来自 23 个国家的患者入组，主要来自美国，但也有欧洲、南美洲和亚洲的患者。微生物学意向治疗（MITT）人群包括 1042 例患者，其中 685 例分离株按照 CLSI 指南在中心实验室（JMI 实验室，北利伯蒂，IA）进行鉴定和药敏试验。比较用的氟喹诺酮类抗生素包括左氧氟沙星和环丙沙星。这些抗生素的耐药性是根据 CLSI 折点来确定的。33.7%的 分离株对左氧氟沙星耐药（LVX-NS）。德拉沙星对耐左氧氟沙星的 、耐甲氧西林金黄色葡萄球菌（MRSA）和甲氧西林敏感的 分离株的 MIC 值均为 0.25μg/ml。德拉沙星对 LVX-NS 分离株以及在喹诺酮耐药决定区（QRDR）有明确突变的分离株具有很高的微生物学反应率。在接受德拉沙星治疗的 249 例患者中，98.4%（245/249）的患者 被清除或假定被清除。在 LVX-NS 分离株和 MRSA 分离株的患者中，也观察到相似的清除率（80/81；98.8%）。接受德拉沙星治疗的患者中，80.6%的患者 被清除或假定被清除，这些患者的 分离株有 S84L 突变和 S80Y 突变。在全球 3 期研究中，这两种突变是最常见的突变。数据表明，德拉沙星可能是治疗由 ABSSSI 引起的感染的一个很好的选择，包括 MRSA 感染，因为这些感染中观察到较高的环丙沙星和左氧氟沙星耐药率。（本文所述的 3 期研究已在 ClinicalTrials.gov 上注册，标识符为 NCT01984684 和 NCT01811732。）
