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慢性化脓性中耳炎局部治疗失败是由于生物膜中的持久性细胞。

Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, California, USA.

Department of Otolaryngology, Head and Neck Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China.

出版信息

Otol Neurotol. 2021 Oct 1;42(9):e1263-e1272. doi: 10.1097/MAO.0000000000003222.

DOI:10.1097/MAO.0000000000003222
PMID:34149028
Abstract

OBJECTIVE

Chronic suppurative otitis media (CSOM) is characterized by a chronically draining middle ear. CSOM is typically treated with multiple courses of antibiotics or antiseptics which are successful in achieving quiescence; however, the disease is prone to relapse. Understanding why these treatment failures occur is essential.

STUDY DESIGN

The minimum inhibitory concentration (MIC), minimal biofilm eradication concentration, and the inhibitory zone were determined for ototopicals and ofloxacin for the laboratory strains and CSOM-derived isolates. The percentage of persister cells and bacterial biofilm formation were measured. Disease eradication was tested in a validated in-vivo model of CSOM after treatment with ofloxacin.

SETTING

Microbiology Laboratory.

METHODS

Basic science experiments were performed to measure the effectiveness of a number of compounds against CSOM bacteria in a number of distinct settings.

RESULTS

The minimal biofilm eradication concentration is higher than is physiologically achievable with commercial preparations, except for povo-iodine. Clincial isolates of CSOM have equivalent biofilm-forming ability but increased proportions of persister cells. Ofloxacin can convert to inactive disease temporarily but fails to eradicate disease in an in-vivo model.

CONCLUSIONS

Higher percentages of persister cells in clinical CSOM isolates are associated with resistance to ototopicals. Current ototopicals, except povo-iodine, have limited clinical effectiveness; however, it is unknown what the maximum achievable concentration is and there are ototoxicity concerns. Fluoroquinolones, while successful in producing inactive disease in the short term, have the potential to encourage antimicrobial resistance and disease recalcitrance and do not achieve a permanent remission. Given these limitations, clinicians should consider surgery earlier or use of clinically safe concentrations of povo-iodine earlier into the treatment algorithm.

摘要

目的

慢性化脓性中耳炎(CSOM)的特征是中耳长期排脓。CSOM 通常采用多种抗生素或防腐剂治疗,这些药物在实现静止状态方面是成功的;然而,该疾病容易复发。了解这些治疗失败的原因至关重要。

研究设计

测定了耳用制剂和氧氟沙星对实验室菌株和 CSOM 来源分离株的最小抑菌浓度(MIC)、最小生物膜清除浓度和抑菌圈。测定了浮游细胞和细菌生物膜形成的百分比。用氧氟沙星治疗 CSOM 的验证体内模型后,测试了疾病的清除情况。

地点

微生物学实验室。

方法

进行基础科学实验,以在多种不同环境下测量多种化合物对 CSOM 细菌的有效性。

结果

除了聚维酮碘之外,生物膜清除最小浓度高于商业制剂生理上可达到的浓度。CSOM 的临床分离株具有等效的生物膜形成能力,但具有更高比例的浮游细胞。氧氟沙星可以暂时将疾病转化为不活跃状态,但在体内模型中不能消除疾病。

结论

临床 CSOM 分离株中更高比例的浮游细胞与对抗生素的耐药性有关。目前的耳用制剂(除了聚维酮碘之外)临床效果有限;然而,不知道最大可达到的浓度是多少,并且存在耳毒性问题。氟喹诺酮类药物虽然在短期内成功地产生不活跃的疾病,但有鼓励抗菌药物耐药性和疾病顽固性的潜力,并且不能实现永久性缓解。鉴于这些局限性,临床医生应更早地考虑手术或更早地将临床安全浓度的聚维酮碘纳入治疗方案。

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