急性外耳道炎——美国与加拿大的抗菌药物耐药性：III期研究结果

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中文摘要

目的： 本研究的目的是表征来自2项载体对照III期临床试验的AOE患者所分离病原体的微生物学特征和抗菌药物敏感性模式，并评估非那沙星滴耳混悬液所达到的病原体清除率。与其他氟喹诺酮类药物（环丙沙星、氧氟沙星）的体外MIC比较作为补充药敏数据报告，并不反映直接的随机临床比较。
方法： 共分析了来自美国、波多黎各和加拿大2项III期临床研究中入组的1234例AOE患者的2683株细菌。标本采集自AOE受试者的外耳。通过结合表型和基因型数据，对每一株回收的细菌分离株进行种水平鉴定。终点最低抑菌浓度（MIC）检测采用临床和实验室标准协会推荐的方法进行。
结果： 治疗前细菌中72.7%为革兰阳性，27.3%为革兰阴性。最常见的细菌分离株为葡萄球菌属（46.7%），其次为假单胞菌属（19.5%）。在金黄色葡萄球菌中检出甲氧西林耐药（MRSA）占17.0%，在表皮葡萄球菌中检出甲氧西林耐药（MRSE）占33.2%。在金黄色葡萄球菌分离株中检出环丙沙星耐药占12.5%，在表皮葡萄球菌分离株中占14.0%。非那沙星清除了86.4%的MRSA分离株和80.6%的MRSE分离株。在接受治疗的患者中，非那沙星清除了74.4%的环丙沙星耐药葡萄球菌属和87.5%的环丙沙星耐药假单胞菌属。
结论： 非那沙星在伴有甲氧西林耐药表皮葡萄球菌和金黄色葡萄球菌的AOE患者中，以及在伴有环丙沙星耐药葡萄球菌属和假单胞菌属的患者中，无论病原体的耐药谱如何，均表现出高清除率。这些体外研究结果连同在载体对照试验中观察到的清除率提示，非那沙星可能在耐药微生物的治疗中具有优势，尤其是在酸性pH条件下。然而，尚未进行直接的临床试验比较。
试验注册： 临床试验注册名称：ClinicalTrials.gov。网址：https://clinicaltrials.gov/。标识符：NCT01535599和NCT01535560。

英文摘要

OBJECTIVE: The goal of this investigation was to characterize the microbiological profile and antimicrobial susceptibility patterns of pathogens isolated from AOE patients of 2 vehicle-controlled Phase III clinical trials and evaluate pathogen eradication rates achieved with finafloxacin otic suspension. In vitro MIC comparisons to other fluoroquinolones (ciprofloxacin, ofloxacin) are reported as supplementary susceptibility data and do not reflect direct randomized clinical comparisons.
METHODS: A total of 2683 bacteria isolated from 1234 AOE patients enrolled in 2 Phase III clinical studies in the United States, Puerto Rico, and Canada were analyzed. Specimens were collected from the external ear of subjects with AOE. Species-level identification for each bacterial isolate recovered was obtained by combining phenotypic and genotypic data. End point minimum inhibitory concentration (MIC) testing was performed using Clinical and Laboratory Standards Institute recommended methods.
RESULTS: 72.7% of the pre-therapy bacteria were Gram-positive and 27.3% Gram-negative. Most frequent bacterial isolates were Staphylococcus spp. (46.7%) followed by Pseudomonas spp. (19.5%). Methicillin resistance was detected in 17.0% of S. aureus (MRSA) and 33.2% of S. epidermidis (MRSE) isolates. Ciprofloxacin resistance was identified in 12.5% of S. aureus and 14.0% of S. epidermidis isolates. Finafloxacin eradicated 86.4% of the MRSA isolates and 80.6% of the MRSE isolates. Finafloxacin eradicated ciprofloxacin-resistant Staphylococcus spp. in 74.4% and ciprofloxacin-resistant Pseudomonas spp. in 87.5% of treated patients.
CONCLUSION: Finafloxacin demonstrated high eradication rates in AOE patients with methicillin-resistant S. epidermidis and S. aureus, as well as in patients with ciprofloxacin-resistant Staphylococcus spp.- and Pseudomonas spp., irrespective of the pathogen's resistance profile. These in vitro findings, together with observed eradication rates in the vehicle-controlled trials, suggest that finafloxacin may offer advantages in the treatment of resistant organisms, particularly under acidic pH conditions. However, direct clinical trial comparisons have not been conducted.
TRIAL REGISTRATION: Clinical trial registry name: ClinicalTrials.gov. URL: https://clinicaltrials.gov/. Identifier: NCT01535599 and NCT01535560.