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Managing recurrent otitis externa in dogs: what have we learned and what can we do better?
管理犬的复发性外耳炎:我们学到了什么，我们可以做得更好?
Tim Nuttall, PhD, MRCVS
翻译：王帆
ABSTRACT
摘要
Recurrent otitis externa is a common problem in dogs. Topical treatment for each flare is successful in the short term, but repeated cycles of inflammation and infection lead to chronic inflammatory changes, pain and aversion, and antimicrobial resistance. These make the flares more frequent and harder to control. Eventually, the changes become irreversible and require a total ear canal ablation/lateral bulla osteotomy or ablative laser surgery. Most ear canal surgery is avoidable if recurrent otitis is properly managed at an earlier stage. This requires a different mindset and approach to these cases, taking advantage of recent research and clinical findings. Most importantly, clinicians must appreciate that all recurrent ear infections in dogs are secondary. To achieve a good long-term outcome, it is essential that all the underlying factors in each case are diagnosed and managed using the primary, secondary, predisposing, and perpetuating framework. This means that the primary condition must be diagnosed and managed, the secondary infection treated, predisposing risks identified and corrected, and the perpetuating factors reversed. Treatment is in 2 phases: induction to get the ears in remission and then long-term maintenance therapy to prevent relapses. Treatment should be appropriate to each dog but will typically involve ear cleaning, topical antimicrobial therapy, and topical or systemic glucocorticoids. Novel treatments for infection and inflammation will offer additional options in the future. Understanding the triggers for recurrent otitis in dogs will help clinicians plan effective management regimens that will make a huge difference to the quality of life of their patients and their owners.
复发性外耳炎是犬的常见问题。每次发作的外部治疗在短期内都是成功的，但炎症和感染的反复循环会导致慢性炎症变化、疼痛和厌恶以及抗微生物药物耐药性。这使得突然发作更加频繁，更加难以控制。最终，这些改变变得不可逆转，需要全耳道消融/外侧鼓泡截骨术或激光消融手术。如果复发性耳炎在早期得到适当处理，大多数耳道手术是可以避免的。这需要利用最近的研究和临床发现，以不同的心态和方法对待这些病例。最重要的是，临床医师必须认识到犬的所有复发性耳部感染都是继发性的。为了获得良好的长期结局，每个病例的所有潜在因素都必须使用原发、继发、易感和持久病因框架进行诊断和管理。这意味着必须诊断和管理原发疾病，治疗继发感染，识别和纠正可能的风险，并逆转长期存在的因素。治疗分为两个阶段:诱导缓解和长期维持治疗以防止复发。治疗应适合每只犬，但通常包括清洁耳朵、外部抗菌治疗以及外部或全身糖皮质激素治疗。感染和炎症的新型治疗方法将在未来提供更多的选择。了解犬复发性耳炎的诱因将有助于临床医师制定有效的管理方案，这将对患犬及其主人的生活质量产生巨大影响。
Introduction
介绍
Otitis externa is common in dogs. Recurrent cycles of inflammation and infection lead to chronic acquired pathological changes that make the flares of infection more frequent and severe. These changes may also drive a switch from Malassezia yeasts and/ or gram-positive bacteria to gram-negative bacteria, particularly Pseudomonas spp Malassezia and bacterial species associated with otitis produce biofilms, which facilitate adherence, promote complex and self-sustaining microbial populations, and inhibit antimicrobial activity. Finally, repeated ineffective treatment courses select for antimicrobial resistance (AMR). Eventually, there are irreversible changes and/or unresponsive infections that require surgical intervention, most commonly total ear canal ablation/lateral bulla osteotomy (TECA/LBO). This may be curative in terms of removing the diseased tissue but substantially increases the cost and complexity of treatment (which can include hemorrhage, pain, surgical site infections, Horner’s and/or vestibular syndrome, and para-aural abscesses).
犬外耳炎很常见。炎症和感染的反复循环导致慢性获得性病理改变，使感染发作更加频繁和严重。这些变化也可能驱动从马拉色菌和/或革兰阳性菌向革兰阴性菌的转变，特别是假单胞菌、马拉色菌，和与耳炎相关的细菌产生生物膜，从而促进黏附，促进复杂和自我维持的微生物群，并抑制抗菌活性。最后，重复无效的疗程选择抗微生物药物耐药性(AMR)。最终会出现不可逆的改变和/或治疗无效的感染，需要手术干预，最常见的是全耳道消融/外侧鼓泡截骨术(TECA/LBO)。从移除病变组织的角度来看，这可能是治愈的方法，但会大大增加治疗的成本和复杂性(包括出血、疼痛、手术部位感染、霍纳综合征和/或前庭综合征以及耳旁脓肿)。
Most ear canal surgery is avoidable if recurrent otitis is correctly diagnosed and managed to prevent the march to irreversible chronic changes. However, this necessitates a thorough understanding of the etiology and pathogenesis of otitis. This review will discuss modern approaches to recurrent otitis in the light of new evidence around inflammatory diseases and the otic microbiome. It will concentrate on otitis externa and only briefly discuss otitis media and interna.
如果复发性耳炎被正确诊断，大多数耳道手术是可以避免的，并设法防止不可逆转的慢性变化。然而，这需要彻底了解耳炎的病因和发病机制。本文将根据炎性疾病和耳部微生物组的新证据，讨论现代治疗复发性耳炎的方法。它将集中于外耳炎，只简要讨论中耳炎和内耳炎。
Definitions
定义
There are no agreed definitions for recurrent and chronic otitis. In our practice, we use the following:
对于复发性和慢性耳炎没有统一的定义。在我们的临床实践中，我们使用以下方法:
• Otitis: inflammation of the pinnae and/or ear canals; this may or may not be associated with infection.
• Ear infection: a clinically significant microbial overgrowth or infection, although in most cases this represents a dysbiosis of the local otic microbiome rather than a true acquired infection (see below).
• Recurrent: clinically significant ear inflammation/infection within 3 months of complete resolution of a previous episode; this may be acute or chronic.
• Acute: otitis without acquired proliferative changes in the ear canals (Figure 1).
• Chronic: otitis with the presence of acquired proliferative changes in the ear canals (Figure 2).
•耳炎:耳廓和/或耳道的炎症;这可能与感染有关，也可能与感染无关。
•耳部感染:临床上明显的微生物过度增殖或感染，但在大多数病例中，这代表了局部耳道微生物群的生态失调，而不是真正的获得性感染(见下文)。
•复发性:前一次发作3个月内出现耳部炎症/感染的临床表现;这可能是急性或慢性的。
•急性:耳道无获得性增生性改变的耳炎(图1)。
•慢性:伴有耳道获得性增生性改变的耳炎(图2)。
Figure 1—Acute erythroceruminous otitis showing inflammation in an ear canal with erythema, vascular swelling, and a ceruminous discharge. There is little cellular proliferation or structural change. The inflammation should respond rapidly to topical and/or systemic glucocorticoids.
图1急性发红耵聍性耳炎，表现为耳道炎症伴皮肤发红、血管肿胀和耵聍分泌物。几乎没有细胞增殖或结构改变。炎症反应对外部和/或全身性糖皮质激素治疗快速有效。
Figure 2—Chronic inflammation in an ear canal with hyperplastic changes in the epidermis, dermis, and ceruminous/sebaceous glands (giving the rough “cobblestone” appearance). This results in a failure of epidermal migration, increased discharge, and stenosis. These changes will start to prevent resolution and, left unchecked, will eventually result in an end-stage ear. This will require more aggressive systemic glucocorticoid treatment.
图2耳道慢性炎症伴表皮、真皮和耵聍/皮脂腺增生性改变(呈现粗糙的“鹅卵石”外观)。这导致表皮迁移失败、分泌物增多和狭窄。这些变化将开始阻止缓解，如果不加以控制，最终将导致“终末期耳道”。这将需要更积极的全身性糖皮质激素治疗。
There Are 2 Distinct Clinical Presentations of Otitis Externa
外耳炎有两种不同的临床表现
Most cases of otitis fall into 1 of 2 distinct clinical presentations:
大多数中耳炎病例有以下两种不同的临床表现之一:
• Erythroceruminous otitis: characterized by erythema with a ceruminous to seborrhoeic discharge (Figure 3). The ears may simply be inflamed, but most cases are associated with Malassezia yeast or staphylococcal bacterial overgrowths; gram-negative bacteria are less common unless there is chronic inflammation and stenosis. These cases tend to be pruritic, but chronically inflamed ears can be painful.
•发红耵聍性耳炎:以发红为特征，伴有蜡样至脂溢性的分泌物(图3)。耳朵可能只是炎症，但大多数病例与马拉色菌或葡萄球菌细菌过度生长有关。革兰阴性菌较少见，除非有慢性炎症和狭窄。这些病例往往会瘙痒，但慢性炎症的耳朵可能会疼痛。
• Suppurative otitis: characterized by erythema, ulceration, and a purulent discharge often with a biofilm (Figure 4). Most cases are associated with neutrophils and Pseudomonas spp with other gram-negative and gram-positive bacteria being less common. Malassezia yeasts are rare in suppurative otitis but show a distinct phenotype that may be associated with IgE-associated Malassezia hypersensitivity and immune-mediated ear canal inflammation (including interface dermatitis). Noninfected suppurative otitis is less common but can be seen with irritant reactions to topical treatments or immune-mediated diseases that affect the ear canal. Suppurative otitis is often very painful.
•化脓性耳炎:以发红、溃疡和常伴有生物膜的脓性分泌物为特征(图4)。大多数病例与中性粒细胞和假单胞菌有关，其他革兰阴性和革兰阳性菌较少见。马拉色菌在化脓性中耳炎中罕见，但表现出独特的表型，可能IgE相关的马拉色菌超敏反应和免疫介导的耳道炎症(包括界面皮炎)相关。非感染性化脓性耳炎较少见，但可与外部治疗的刺激反应或影响耳道的免疫介导性疾病有关。化脓性耳炎常很痛。
Figure 3—Erythroceruminous otitis characterized by erythema and a ceruminous discharge. These cases are most commonly associated with Malassezia yeast or staphylococcal bacterial overgrowth.
图3发红耵聍性耳炎，以发红和耵聍分泌物为特征。这些病例最常与酵母菌或葡萄球菌过度增殖有关。
Figure 4—Suppurative otitis with ulceration, a purulent discharge, and biofilm formation (note the biofilm matted into the surrounding hairs). These cases usually involve a Pseudomonas spp infection.
图4化脓性中耳炎伴溃疡，化脓性分泌物，并形成生物膜(注意生物膜缠结在周围毛发中)。这些病例通常涉及假单胞菌感染。
All Recurrent Ear Infections Are Secondary
所有复发性耳部感染都是继发性的
All recurrent ear infections are secondary to underlying factors. It is important to note that while published “cure” rates for topical antimicrobial/ glucocorticoid ear medications are very high (often over 90%), these refer to the individual episode of ear infection and not the underlying otitis. Recurrence does not mean that the treatment failed, but it does mean that the underlying triggers for the otitis and ear infections were not managed. Repeating treatment with the same or a different product will only give short-term relief: this will not alter the pattern of relapsing inflammation and infection. It is essential that the underlying triggers are diagnosed and managed for a successful long-term outcome.
所有复发性耳部感染均继发于潜在病因。值得注意的是，虽然已发表的外用抗微生物/糖皮质激素耳部药物的“治愈率”非常高(通常超过90%)，但治愈率是指单独的耳部感染发作，而不是潜在的耳炎。复发并不意味着治疗失败，但确实意味着耳炎和耳部感染的潜在诱因未得到控制。重复使用相同或不同的产品治疗只能短期缓解:这不会改变复发性炎症和感染的模式。为获得成功的长期预后，诊断和治疗潜在诱因至关重要。
There Are Primary, Predisposing, and Perpetuating Triggers for Otitis Externa
外耳炎有原发、易感的和持久诱因
The development and progression of recurrent and/or chronic otitis are multifactorial. The primary-predisposing-perpetuating (PPP) system is a well-established framework to identify the primary, predisposing, and perpetuating factors in each case. More recently, this has been modified to a PSPP/PPPS system to include secondary (S) infections (see above).
复发性和/或慢性耳炎的发生和进展是多因素的。原发-易感-持久(PPP)系统是一个完善的框架，用于识别每种病例的原发性、易感性和持久性因素。最近，这已被修改为PSPP/PPPS系统，包括了继发感染(见上文)。
Primary triggers in otitis externa
外耳炎的原发诱因
Primary factors trigger ear inflammation and, therefore, must be capable of inducing inflammation in otherwise healthy skin or, less commonly, suppressing the immune system to the extent that potential pathogens can establish in the ear canals (Table 1).
原发因素是耳部炎症，因此，必须能够在其他健康的皮肤上诱发炎症，或者，不太常见的是，潜在病原体可以在耳道中一定程度上抑制了免疫系统(表1)。
There is a wide range of potential primary triggers of otitis externa, but it makes no sense to investigate all of these in every case. A careful and thorough review of the signalment, history, and clinical signs (making sure that the whole dog is examined, not just the ears) will narrow the differential diagnosis allowing cost- and time-efficient use of appropriate diagnostic steps and treatment. For example, a 3-year-old Labrador Retriever with a history of recurrent bilateral erythroceruminous otitis with pruritus and erythema of its ventral pinnae, interdigital skin, and flexor joint surfaces is highly likely to have atopic dermatitis and/or an adverse food reaction. A Cocker Spaniel with acute and painful unilateral otitis after exercising in long grass is most likely to have a grass awn lodged in the ear canal.
外耳炎的潜在原发诱因有很多，但对每个病例都进行调查是没有意义的。对特征、病史和临床症状进行仔细和彻底的回顾(确保对犬全身进行检查，而不仅仅是对耳部)将缩小鉴别诊断的范围，以便以成本和时间高效率地使用适当的诊断步骤和治疗。例如，一只3岁的拉布拉多寻回犬有反复发作的双侧发红耵聍性耳炎病史，伴有瘙痒和耳廓腹侧、指间皮肤和屈关节表面皮肤发红，极有可能患特应性皮炎和/或食物副反应。可卡犬在长草中运动后患急性和疼痛的单侧耳炎，最有可能耳道中卡一个草芒。
It is very important to take a holistic view of each case: clinicians must recognize and understand the clinical significance of findings that help identify the underlying condition or at least narrow the options. It is crucial to fully examine both ears even in cases of apparent unilateral otitis. Bilateral otitis is more common, but local predisposing factors (see below) can make the otitis more common or more severe in one ear than the other. The subsequent chronic acquired perpetuating changes (see below) lead to further divergence in severity between the 2 ears. In our practice, most referrals with unilateral otitis actually have bilateral disease. This changes the most likely differentials as well as the approach to investigation and treatment. While some cases of atopic dermatitis may present with unilateral otitis, it is important to consider other more local triggers in these cases.
对每个病例进行整体评估是非常重要的:临床医师必须认识和理解这些发现的临床意义，这些发现有助于识别潜在疾病或至少缩小选择范围。即使在明显的单侧耳炎病例中，全面检查双耳也是至关重要的。双侧耳炎更常见，但局部易感因素(见下文)可使一侧耳炎比另一侧耳炎更常见或更严重。随后的慢性获得性持久性改变(见下文)，导致两耳之间的严重程度进一步不同。在我们的临床实践中，大多数单侧耳炎转诊患犬实际上患有双侧耳炎。这改变了最有可能的鉴别诊断以及调查和治疗方法。虽然某些特应性皮炎病例可能出现单侧耳炎，但在这些病例中，重要的是考虑其他更局部的诱因。
Predisposing factors in otitis externa
外耳炎的易感因素
Predisposing factors rarely (if ever) trigger otitis by themselves, but they make the otitis more likely to occur or more likely to progress in an animal with a primary condition (Table 2). These are mostly anatomical/conformational or (less commonly) lifestyle or management factors.
易感因素本身很少(如果有的话)引发耳炎，但它们使耳炎更容易发生或更容易在具有原发性疾病的动物中进一步发展(表2)。这些因素主要是解剖学/构象或(不太常见的)生活方式或管理因素。
Cocker Spaniels, especially American Cocker Spaniels, have a greater density of ceruminous glands than other breeds. This predisposes them to ceruminous gland hyperplasia, ectasia, and cyst formation that results in the rapid development of chronic changes (ie, perpetuating factors, see below). These changes facilitate bacterial infections and are less responsive to glucocorticoid therapy, which may be why these breeds rapidly progress to end-stage otitis requiring TECA-LBO (Figure 5).
可卡犬，尤其是美国可卡犬，比其他品种有更大密度的耵聍腺。这使他们易形成患耵聍腺增生、扩张和囊肿，导致快速出现慢性改变(即，持久因素，见下文)。这些变化有利于细菌感染，对糖皮质激素治疗反应较差，这可能是这些品种迅速发展为终末期耳炎需要TECA-LBO的原因(图5)。
Chinese Shar Peis have a tightly opposed rostrally facing pinna that is partly the outcome of a twist in the vertical ear canal. In some dogs, this results in stenosis at that point. Prophylactic vertical ear canal surgery may be of benefit to these dogs.However, this must be done before chronic inflammatory changes develop in the horizontal ear canal.
中国沙皮犬的耳廓反向朝向吻侧紧贴，这在一定程度上是垂直耳道扭曲的结果。在一些犬上，这会导致该部位狭窄。预防性垂直耳道手术可能对这些犬有益。然而，这必须在水平耳道发生慢性炎症变化之前进行。
Perpetuating changes in otitis externa
外耳炎的持久改变
Perpetuating changes are chronic acquired pathological changes in the ear canals that prevent resolution. Early changes include nodular epidermal and glandular hyperplasia giving the ear canals a “cobblestone” appearance (Figures 2 and 6). Later changes include further epidermal and dermal hyperplasia and thickening, ear canal stenosis and occlusion, fibrosis, and mineralization. This can also result in tympanic membrane rupture, otitis media, and cholesteatoma formation.
持久改变是耳道内的慢性获得性病理变化，会阻碍疾病消退。早期变化包括表皮结节和腺体增生，使耳道呈现“鹅卵石”外观(图2和图6)。后期变化包括进一步的表皮和真皮增生和增厚、耳道狭窄和阻塞、纤维化和矿化。这也可能导致鼓膜破裂、中耳炎和胆脂瘤形成。
It is essential that early chronic acquired pathological changes are recognized and treated. This gives the best chance of a good long-term outcome. More severe changes become progressively harder to treat increasing the complexity, complications, and cost.
早期慢性获得性病理改变的识别和治疗是至关重要的。这是获得良好长期结果的最佳机会。更严重的改变变得越来越难以治疗，增加了复杂性、并发症和成本。
Assessing the Extent and Severity of Chronic Pathological Changes in Otitis Externa
外耳炎慢性病理改变严重程度评估
Acquired perpetuating changes must be reversed during the initial induction phase of treatment (see below). Treatment planning therefore needs to include a thorough assessment of their extent and severity. Traditionally, this has been based on diagnostic imaging, but clinicians should also use their clinical acumen (especially if finances or resources are limited).
获得性持久改变必须在治疗的初期诱导阶段逆转(见下文)。因此，治疗计划需要包括对其严重程度的全面评估。传统上，这是基于影像诊断，但临床医生也应该利用他们的临床敏锐度(特别是在财政或资源有限的情况下)。
Healthy ear canals are thin cartilage tubes lined by skin; they should be freely mobile, pliable, and free from discharge, pruritus, and pain. Affected ear canals will become progressively immobile, firm, and painful. Otoscopic examination should reveal a thin, smooth, and pale lining with scant ceruminous discharge and a translucent, taut, and slightly concave tympanic membrane. Chronic changes include a roughened (cobblestone-like) appearance, ceruminous hyperplasia, cysts and polyps, thickening and stenosis, increased discharge, and tympanic membrane thickening and inflammation (myringitis), opacity, distortion, and/or rupture.
健康的耳道是薄的软骨管腔内衬着皮肤;它们应能自由活动、柔韧、无分泌物、无瘙痒和疼痛。患病耳道将逐渐变得不灵活、坚硬和疼痛。耳镜检查应可见薄的、光滑、皮肤苍白、有少量的耵聍分泌物、透亮、紧致、鼓膜微凹。慢性改变包括粗糙(鹅卵石样)外观、耵聍增生、囊肿和息肉、增厚和狭窄、分泌物增多以及鼓膜增厚和炎症(鼓膜炎)、混浊、变形和/或破裂。
Diagnostic imaging techniques include radiography, computed tomography (CT), and magnetic resonance imaging (MRI) (Table 3). CT is the most cost-effective modality; the bone and soft-tissue windows with contrast enhancement give highly detailed information about ear canal inflammation and chronic changes (including thickening, ceruminous hyperplasia, stenosis, and mineralization), polyps and tumors, discharge, tympanic membrane integrity, otitis media, and otitis interna.
影像诊断技术包括X光、计算机断层扫描(CT)和磁共振成像(MRI)(表3)。CT是性价比最高的方法;骨窗和软窗，结合增强对比，能提供非常详细的信息，包括耳道炎症和慢性改变(包括增厚、耵聍增生、狭窄和矿化)、息肉和肿瘤、分泌物、鼓膜完整性、中耳炎和内耳炎。
Phases of Treatment: Induction and Remission
治疗阶段:诱导和缓解
Despite the complex multifactorial nature of otitis externa (see the PSPP system above), recurrent otitis externa can be regarded in its basic form as a progressive chronic inflammatory process. This is similar to canine atopic dermatitis (AD), where the pruritus and inflammation are the result of a complex immunologic cascade that varies at different stages of the condition as well as between breeds and individual dogs. Moreover, canine AD is the most frequent primary factor in recurrent otitis externa factors.
尽管外耳炎具有复杂的多因素性质(见上文的PSPP系统)，但复发性外耳炎的基本形式可视为慢性炎症进一步发展的过程。这与犬特应性皮炎(AD)类似，其中瘙痒和炎症是复杂的免疫级联反应的结果，这种反应在疾病的不同阶段以及犬种和个体之间都有所不同。此外，犬AD是复发性外耳炎最常见的原发因素。
Management recommendations for canine AD have evolved to consider this process and now recognize 2 distinct phases of treatment:
1. Phase 1 reactive therapy: the treatment of existing acute and/or chronic lesions and/or infection to clinical remission.
2. Phase 2 proactive therapy: long-term regular therapy to maintain remission and prevent flares.
犬AD的管理指南已经考虑到这一过程，现在认识到两个不同的治疗阶段:
1. 第1阶段对症治疗:治疗现有的急性和/或慢性病变和/或感染，使其临床缓解。
2. 第2阶段主动治疗:规划长期治疗，以维持缓解和防止急性发病。
Clinicians must understand the precise mode of action and spectrum of activity of the different treatment options for otitis to optimize treatment for an individual patient at each stage of their disease. In contrast, inappropriate use of medication and/or a failure to move from induction to maintenance will increase the risk of treatment failure and progression to medically irreversible chronic otitis.
临床医生必须了解耳炎不同治疗方案的确切作用模式和有效范围，以便在疾病的每个阶段为单个患犬优化治疗。相反，药物使用不当和/或未能从诱导转向维持将增加治疗失败风险和进一步发展为不可逆的慢性耳炎。
The therapeutic options for otitis can be grouped into antimicrobials, ear cleaning, and anti-inflammatory treatments. These are considered below, emphasizing the appropriate choices for induction and maintenance therapy.
耳炎的治疗选择可分为抗生素、洗耳液和抗炎治疗。下面考虑这些，强调诱导和维持治疗的适当选择。
When Is an Infection Not an Infection? When It Is a Dysbiosis
什么时候感染不是感染?菌群失调的时候
Cytology and culture studies have shown that most ear infections are associated with Malassezia yeasts, Staphylococcus pseudintermedius, or Pseudomonas aeruginosa. However, traditional sample and culture methods favor a limited number of easily isolated organisms. High-throughput genomic sequencing techniques have revolutionized our understanding by revealing the rich complex microbial population of the ear canals and the dynamic changes seen in otitis.
细胞学检查和细菌培养研究表明，大多数耳部感染与马拉色酵母菌、假中间型葡萄球菌或铜绿假单胞菌有关。然而，传统的样品和培养方法有利于数量有限的易于分离的生物体。通过高通量基因组测序技术揭示了耳道丰富复杂的微生物种群和耳炎中看到的动态变化，彻底改变了我们的理解。
The ear canal microbiome is a mix of bacterial and fungal microbiotas. Microbiomes vary between individuals, but diversity seems to be key. Diversity reflects the richness (ie, the total number of microbial species present) and evenness (ie, the relative abundance of each species in the microbial community) of the microbial population.
耳道微生物群是细菌和真菌微生物群的混合物。微生物组因个体而异，但多样性似乎是关键。多样性反映了微生物种群的丰富度(即存在的微生物物种总数)和均匀度(即微生物群落中每个种类的相对量)。
The bacterial microbiota of canine ear canals shows high diversity with several abundant phyla, including Proteobacteria, Actinobacteria, Firmicutes, Fusobacteria, and Bacteroidetes.Inflamed ears show lower species richness (diversity) with approximately 70% showing a bacterial, 16% a fungal overgrowth, and 7% a mixed overgrowth. The most important organisms are Malassezia pachydermatis, Staphylococcus pseudintermedius, and Staphylococcus schleiferi, but more unusual organisms not previously implicated in otitis include anaerobes (Finegoldia magna, Peptostreptococcus canis, and Porphyromonas cangingivalis) and Ralstonia species, whereas Escherichia coli and some Porphyromonas (including P cangingivalis) are abundant in healthy ears. In contrast, 1 study found few differences between allergic and nonallergic German Shepherd Dogs with Actinobacteria (especially Macrococcus) most abundant in nonallergic dogs and Proteobacteria (especially Sphingomonas) in allergic dogs.
犬耳道菌群具有高度多样性，包括变形菌门、放线菌门、厚壁菌门、梭杆菌门和拟杆菌门等。有炎症的耳朵表现出较低的物种丰富度(多样性)，约70%表现为细菌过度增殖，16%为真菌过度增殖，7%为混合菌过度增殖。最重要的微生物是厚皮马拉色菌、假中间型葡萄球菌和施氏葡萄球菌，但之前未涉及到的更罕见的微生物包括厌氧菌(大芬戈尔德菌、犬消化链球菌和犬牙龈卟啉单胞菌)和罗尔斯通菌属，而大肠埃希菌和一些卟啉单胞菌(包括犬牙龈卟啉单胞菌)在健康耳道中大量存在。相反，一项研究发现，在过敏和非过敏的德国牧羊犬之间，放线菌门(特别是巨大球菌)在非过敏的犬中最多，而变形菌门(特别是鞘氨醇单胞菌)在过敏的犬中最多。
The fungal microbiota is again rich, with up to 10 phyla identified in ears and skin, although it is dominated by Malassezia spp. Affected ears show a loss of diversity and shift to Malassezia yeasts, but the relative abundance of different species may be as important as the diversity per se. In dogs, M globosa and M restricta predominate on healthy skin whereas M pachydermatis were associated with atopic skin. More virulent M pachydermatis have also been associated with otitis externa in dogs. Differences in lipid dependency and altered lipid profiles in healthy and affected skin and ears may therefore influence population shifts. This may explain why some breeds and individuals are more prone to Malassezia-associated otitis than others. Manipulating lipid profiles to support less pathogenic Malassezia species/strains may be beneficial, but further studies are required.
真菌菌群再次丰富，在耳道和皮肤中鉴定出多达10个菌门，但以马拉色菌属为主。患耳显示出缺乏多样性和转向马拉色菌酵母菌，但不同物种的相对丰度可能与多样性本身一样重要。在犬的健康皮肤中，球形马拉色菌和限制型马拉色菌占多数，而厚皮马拉色菌与特应性皮炎皮肤相关。更有毒力的厚皮马拉色菌也与犬的外耳炎相关。因此，在健康和患病皮肤和耳道中，脂质依赖性的差异以及脂质谱的改变可能影响数量的变化。这可能解释了为什么一些品种和个体比其他品种更容易患马拉色菌相关性耳炎。控制脂质谱以支持致病性较低的马拉色菌种/菌株可能有益，但需要进一步研究。
Whether altered bacterial and fungal population structures (the varieties and relative abundance of bacterial and fungal genera and species) are a cause or effect of atopic dermatitis and/or otitis is unclear. Influences include disease status, inflammation, household, sex, body site, and breed. There is likely to be mutual interaction between skin barrier function, cutaneous immunity, and the microbiome. Loss of diversity leads to staphylococcal, Malassezia, and Pseudomonas spp-dominated populations. Once these reach a critical threshold, they may contribute to ongoing inflammation and epidermal changes through the exclusion of less pathogenic organisms, expression of proinflammatory mediators, and (in some atopic individuals) sensitization and specific IgE production. Therefore, preserving microbiome diversity is a key part of long-term maintenance therapy. Interestingly, topical 2% chlorhexidine/2% miconazole treatment on the skin, topical mometasone in ears, and systemic glucocorticoid and ciclosporin for the skin preserve fungal and bacterial microbiota diversity.
目前尚不清楚改变的细菌和真菌种群结构(细菌和真菌属和种的种类和相对丰度)是否是特应性皮炎和/或耳炎的病因或影响。影响因素包括疾病状态、炎症、家庭、性别、机体部位和品种。皮肤屏障功能、皮肤免疫和微生物群之间可能存在相互作用。缺乏多样性导致以葡萄球菌属、马拉色菌属和假单胞菌属为主。一旦达到临界阈值，它们可能通过以下方式促进持续的炎症和表皮变化:排斥较低致病性微生物、表达促炎介质，以及(在一些特应性个体中)致敏和产生特异性IgE。因此，保持微生物组多样性是长期维持治疗的关键部分。有趣的是，皮肤治疗外用2%氯己定/2%咪康唑，耳部外用莫米松，以及全身性应用糖皮质激素和环孢素可保护皮肤的真菌和细菌菌群多样性。
Cultures and Antimicrobial Susceptibility Tests: Are They Useful in Otitis Externa?
培养和药敏试验:对外耳炎有用吗?
Cultures and antimicrobial susceptibility tests (ASTs) are of limited benefit in otitis externa. Most cases are associated with Malassezia, Staphylococcus, or Pseudomonas spp, which are easily differentiated on cytology (yeasts, cocci, and rods, respectively). Appropriate empirical treatment can then be selected. ASTs cannot be used to reliably select appropriate antimicrobials as the results are very poorly predictive of the response to topical treatment. The breakpoints used to determine sensitivity and resistance assume systemic treatment and are in microgram per milliliter ranges: this does not reflect topical treatments, which can achieve milligram per milliliter concentrations in the ear canals. Therefore, infections listed as resistant to antimicrobials in microgram per milliliter concentrations can be sensitive at milligram per milliliter concentrations, although this is not guaranteed with high-level acquired resistance. A sensitive result, moreover, does not guarantee treatment success as the laboratory AST will not reflect local factors that can affect efficacy (eg, ongoing inflammation, discharge, biofilm, ear canal stenosis, and other primary, predisposing, and perpetuating factors).
培养和抗生素药敏试验(AST)对外耳炎的益处有限。大多数病例与马拉色菌属、葡萄球菌属或假单胞菌属相关，这三种菌在细胞学上很容易鉴别(分别为酵母菌、球菌和杆菌)。然后可以选择适当的经验性治疗。AST不能被可靠地用于选择合适的抗生素，因为其结果对外部治疗效果的预测性非常差。用于确定敏感性和耐药性的折点设定是为了全身性治疗，并且为微克/ ml范围:这并不反映外部治疗，外部治疗在耳道内可达到毫克/ ml浓度。因此，被列为对抗生素耐药(微克/毫升)的感染在毫克/毫升浓度时可能敏感，但不能保证高水平的获得性耐药。此外，敏感的结果并不能保证治疗成功，因为实验室AST不能反映影响疗效的外部因素(如持续的炎症、分泌物、生物膜、耳道狭窄和其他原发、易感和持久因素)。
Cultures may be helpful where precise identification is needed to select appropriate empirical therapy. An example would be where organisms with unusual morphology (eg, coryneforms, cocco-bacilli, filaments, yeasts, hyphae, etc) are seen on cytology raising suspicion of rare infections (eg, unusual bacteria, Candida yeasts, Aspergillus hyphae, etc). Specific risk factors for Aspergillus spp include immunosuppression, otic foreign bodies, and prior antibiotic use, which can be used to prompt cytology and culture. Culture can also be used to differentiate rods when considering leave-in products containing florfenicol; this is effective against E coli, Klebsiella, Proteus spp, etc, but not Pseudomonas spp.
在需要精确识别以选择合适的经验性治疗的情况下，培养可能有帮助。例如，细胞学检查发现具有特殊形态的微生物(如棒状杆菌、球杆菌、细丝、酵母菌、菌丝等)，怀疑罕见感染(如罕见细菌、假丝酵母菌、曲霉菌菌丝等)。曲霉菌的特定危险因素包括免疫抑制、耳部异物和既往使用抗生素，这些因素可提示进行细胞学检查和培养。当考虑使用含有氟苯尼考的耳药时，培养也可用于鉴别杆菌;对大肠杆菌、克雷伯菌、变形杆菌等有效，但对假单胞菌无效。
Topical Antimicrobials and Antimicrobial Stewardship
外用抗生素和抗生素管理
Antibiotic treatment guidelines often group the drugs into first-, second-, and third-line choices. This reflects the importance of antibiotics to human and veterinary healthcare. In 2019, The European Medicines Agency categorized all antimicrobials into 4 groups for use in animals: A, avoid; B, restrict; C, caution; and D, prudence (https://www.ema.europa.eu/en/documents/report/infographiccategorisation-antibiotics-use-animals-prudentresponsible-use_en.pdf;accessed December 28, 2022). Wherever possible, drugs in category D are used in preference to those in categories C, B, and A (Table 4). The aim is to reduce the selection pressure for AMR and preserve the efficacy of these drugs for the future.
抗生素治疗指南通常将药物分为一线、二线和三线选择。这反映了抗生素对人类和兽医卫生保健的重要性。2019年，欧洲药品管理局将所有用于动物的抗微生物药物分为4类:A，避免使用;B,限制使用;C、谨慎使用;D，审慎使用(https://www.ema.europa.eu/en/documents/report/infographiccategorisation-antibiotics-use-animals-prudentresponsible-use_en.pdf;accessed 2022年12月28日)。在可能的情况下，D类药物的使用优先于C、B和A类药物(表4)。目的是减少对AMR的选择压力，并为未来保留这些药物的疗效。
However, this concept is based around systemic antibiotic treatment, which affects the whole bacterial microbiota and not just the site of infection. For example, today’s multidrug resistance (MDR) E coli urinary tract infection could have been selected for by the course of antibiotics given last month for a skin infection. It is likely that topical treatment has less impact than systemic treatment as local application to confined sites such as the ear canals will result in less collateral damage to microbiomes at other sites. Nevertheless, antimicrobial stewardship is a professional responsibility, and this may begin to influence topical treatment choices.
然而，这一概念是基于全身性抗生素治疗，它影响整个细菌微生物群，而不仅仅是感染部位。例如，今天的多重耐药(MDR)大肠杆菌尿路感染可以通过上个月针对皮肤感染给予的抗生素疗程来选择。外部治疗的影响可能比全身治疗小，因为外部应用于狭窄部位(如耳道)对其他部位微生物群的附带损害较小。然而，抗生素管理是一项专业责任，这可能开始影响外部治疗的选择。
Antifungals of the azole (eg, clotrimazole, miconazole, or posaconazole), allylamine (terbinafine), and polyene (nystatin) classes are usually effective in Malassezia yeast-associated otitis. However, clinically significant resistance to systemic and topical azole treatment is being reported.
唑类抗真菌药物(如克霉唑、咪康唑或泊沙康唑)、烯丙胺类抗真菌药物(特比萘芬)和多烯类抗真菌药物(制霉菌素)通常对马拉色酵母菌相关的耳炎有效。然而，对全身和外部唑类治疗的临床显著耐药也有报道。
Without better antimicrobial stewardship, further selection for antibiotic and antifungal resistance is likely. One area of concern is using polyvalent topical ear medications that contain antibiotics and antifungals to treat otitis associated with Malassezia yeasts or bacteria only. Using cytology and more specifically targeted topical therapy will help improve antimicrobial stewardship. For example, Danish and other Nordic national treatment guidelines advise first-line therapy with an antimicrobial cleanser and topical or systemic glucocorticoids in these cases. In addition, diagnosing and managing the underlying factors driving ear infections will reduce the need for repeated treatment.
如果没有更好的抗生素管理，可能会进一步针对抗生素和抗真菌耐药性进行选择。令人担忧的一个领域是使用含有抗生素和抗真菌药物的多价外用耳药治疗与马拉色菌或细菌相关的耳炎。使用细胞学检查和更有针对性的外部治疗将有助于改善抗生素管理。例如，丹麦和其他北欧国家治疗指南建议对这些病例采用抗菌清洁剂和外用或全身性糖皮质激素作为一线治疗。此外，诊断和管理导致耳部感染的潜在因素将减少重复治疗的需求。
Pseudomonas Infections
假单胞菌感染
Pseudomonas spp ear infections are challenging; Pseudomonas spp show widespread inherent resistance, mutate and develop acquired resistance rapidly, and readily form biofilms. Chronic MDR and biofilm-associated infections can be very difficult to eliminate.
假单胞菌耳部感染具有挑战性;假单胞菌表现出广泛的固有耐药，迅速发生突变并产生获得性耐药，极易形成生物膜。慢性MDR和感染相关的生物膜很难消除。
Most infections involve Pseudomonas aeruginosa, although other species can be isolated. These are a type of common source infection (ie, associated with exposure of susceptible individuals to a fomite/vehicle or vector contaminated by an infectious organism). Pseudomonas spp are common and widespread in any wet environment, which can include wet outdoor habitats as well as indoor sources such as washing facilities, drains, water, and food bowls. Other reservoirs important in veterinary healthcare include improperly cleaned and dried equipment, shampoos/ear cleaners, disinfectants, multidose vials, and other solutions. In addition, some dogs carry their own Pseudomonas bacterial population where conformation and other factors provide a suitable moist and protected habitat. Examples include lip folds, facial or body folds, and perivulval folds.
大多数感染涉及铜绿假单胞菌，但也可分离出其他种类的铜绿假单胞菌。这是一种常见的感染源(即易感个体暴露于被感染源污染的污染物/媒介或患病动物)。假单胞菌在任何潮湿环境中常见且广泛，包括潮湿的室外栖息地以及洗涤设施、下水道、水和饭碗等室内来源。其他在兽医保健中很重要的蓄水池包括清洗和干燥不当的设备、香波/洗耳液、消毒剂、多剂量小瓶和其他溶液。此外，一些犬携带自己的假单胞菌群，结构和其他因素提供了一个合适的潮湿和受保护的栖息地。包括唇部褶皱、面部或机体褶皱和外阴周围褶皱。
Exposure to Pseudomonas species is likely to be frequent, but ear infections are uncommon and opportunistic, requiring specific risk factors that allow the Pseudomonas bacteria to colonize and proliferate. Therefore, infections are secondary (see the PSPP discussion above) and primary Pseudomonas bacterial otitis is rarely (if ever seen). The most common primary causes are atopic diseases, followed by masses, endocrinopathies, and autoimmune diseases. Pseudomonas-associated otitis develops more quickly if there was a mass or autoimmune disease, as compared with atopic disease and endocrinopathies.
患犬可能经常暴露于假单胞菌，但耳部感染并不常见，而且是机会性感染，需要特定的危险因素才能使假单胞菌定殖和增殖。因此，感染是继发性的(见上文对PSPP的讨论)，原发性假单胞菌细菌性耳炎罕见(如果见过的话)。最常见的原发病因是特应性疾病，其次是肿块、内分泌疾病和自体免疫性疾病。与特应性疾病和内分泌疾病相比，有肿块或自体免疫性疾病的假单胞菌相关性耳炎发展更快。
Diagnosis of Pseudomonas bacterial otitis is straightforward; most present with a severe suppurative otitis with rod bacteria and neutrophils on cytology. Biofilm (see below) formation is common. If necessary, the Pseudomonas spp can be confirmed on culture but remember that the AST results will be poorly predictive of the outcome of topical treatment (see above).
假单胞菌细菌性耳炎的诊断很简单;大多数患犬表现为严重的化脓性耳炎，细胞学检查可见杆菌和中性粒细胞。生物膜(见下文)形成常见。必要时，可通过培养证实假单胞菌属，但请记住，AST结果对外部治疗结局的预测效果欠佳(见上文)。
Pseudomonas bacterial otitis should be aggressively treated from the outset (Table 5). The best chance of a good outcome is with the first round of treatment; multiple failed treatments select for MDR and biofilm formation. Topical therapy is generally more effective as systemic treatment may not adequately penetrate the inflamed ear canals and lumen. However, systemic antibiotics may be necessary where a topical treatment is not feasible; in this case, the antibiotics should be selected on the basis of culture and AST using the highest safe doses possible to minimize the risk of treatment failure (especially in chronic otitis and/or with biofilms). Effective analgesia is essential; Pseudomonas bacterial otitis is usually very painful and failure to provide adequate pain relief will compromise effective topical treatment (as well as being unethical). NSAIDs should generally be avoided as many cases will require concurrent glucocorticoid therapy to manage primary and perpetuating problems; safe options in these cases include paracetamol (acetaminophen), tramadol, bedinvetmab, and/or gabapentin.
应从一开始就对假单胞菌细菌性耳炎进行积极治疗(表5)。获得良好结局的最佳机会是在第一轮治疗中;多次失败的治疗选择了MDR和生物膜形成。外部治疗通常更有效，因为全身治疗可能无法充分穿透发炎的耳道和耳腔。然而，如果外部治疗不可行，则可能需要全身使用抗生素;在这种病例中，应根据培养和AST选择抗生素，使用尽可能高的安全剂量，以最大限度地降低治疗失败的风险(特别是慢性耳炎和/或有生物膜的患犬)。有效镇痛至关重要;假单胞菌细菌性耳炎通常非常疼痛，不能提供足够的疼痛缓解将影响有效的外部治疗(以及不道德)。通常应避免使用NSAID，因为许多病例需要同时使用糖皮质激素治疗原发性和持久问题;在这些病例中，安全的选择包括对乙酰氨基酚(扑热息痛)、曲马多、贝地维单抗（bedinvetmab）和/或加巴喷丁。
It is essential that a thoroughly holistic approach is taken in these cases to address the infection alongside the primary, predisposing, and perpetuating triggers for the otitis. Successful treatment needs an effective integrated approach. Complex cases may need a referral to a specialist.
重点是在这些病例中，采取彻底的整体方法来解决感染以及耳炎的原发、易感和持久因素。成功的治疗需要有效的综合方法。复杂的病例可能需要转诊给专科医生。
Epidermal Migration and Ear Cleaning
表皮迁移和耳道清洁
Production and clearance of cerumen are normally in balance. Epidermal migration results in the outward movement of desquamated cells, cerumen, and debris from the tympanic membrane to the pinnae. However, epidermal migration may be limited by excessively hairy ear canals and/or individual variation. In addition, epidermal migration breaks down in otitis allowing desquamated cells, cerumen, and debris to build up. Ear cleaning is therefore essential in managing otitis. In 1 study of a ceruminolytic/ceruminosolvent ear cleaner in erythroceruminous otitis, cleaning resulted in improved clinical and cytological scores, decreased debris, and altered lipid profiles. The latter effect may promote a more diverse microbiome as a topical “prebiotic.” However, using the correct ear cleaner and technique is important to avoid compromising the clinical outcome. Clinicians should therefore be familiar with the properties of ear cleaners and the pros and cons of ear cleaning techniques (Tables 6 and 7).
耵聍的产生和清除通常是平衡的。表皮的迁移导致脱落细胞、耵聍和碎片从鼓膜向外移动至耳廓。然而，耳毛过多和/或个体变异可能限制表皮的迁移。此外，在耳炎中，表皮迁移被破坏，导致脱落细胞、耵聍和碎片形成。因此，耳道清洁对于治疗耳炎至关重要。在一项关于耵聍溶解剂/耵聍溶解洗耳液治疗发红耵聍性耳炎的研究中，清洁可改善临床和细胞学评分，减少碎屑，并改变脂质量。后一种作用可能作为局部“益生元”促进菌群更多样性。然而，使用正确的洗耳液和技术是避免影响临床结果的重要因素。因此，临床医师应熟悉洗耳液的特性以及洗耳技术的优缺点(表6和7)。
Foaming ear cleaners containing carbamides lift debris off the ear canal surface and break up material to ease cleaning and flushing. However, dogs can find the sound and sensation disturbing, so these are best used in-clinic prior to other procedures such as a deep ear flush.
含有尿素的泡沫洗耳液可以清除耳道表面的碎片，分解物质，以方便清洁和冲洗。然而，犬会听到声音和有不安的感受，所以这些最好在诊所使用，在其他操作前使用，如深度冲洗耳道。
Antimicrobial compounds in ear cleaners can retard microbial proliferation. Cleaners with isopropyl alcohol, parachlorometaxylenol, chlorhexidine, hypochlorous acid, and a low pH seem to be most effective. Tris-EDTA at 50 mg/mL can show additive activity with chlorhexidine, aminoglycosides, and fluoroquinolones (see above). The inclusion of mono- and polysaccharides can reduce microbial adherence to keratinocytes.
洗耳液中的抗菌成份可以抑制微生物的增殖。含有异丙醇、对氯间二甲苯酚、氯己定、次氯酸和低pH值的洗耳液似乎是最有效。50 mg/mL的Tris-EDTA与氯己定、氨基糖苷类和氟喹诺酮类药物同时使用显示活性增加(见上文)。包含单糖和多糖可减少微生物对角质形成细胞的粘附。
Most ear cleaners are potentially ototoxic and few (aside from squalene) are indicated for use with a ruptured tympanic membrane. Alcohols and acids may also irritate inflamed or ulcerated ear canals.
大多数洗耳液可能有耳毒性，很少(除了角鲨烷)适用于鼓膜破裂的患犬。酒精和酸也可能刺激发炎或溃疡的耳道。
Biofilms
生物膜
Biofilms are common; they will form on virtually any nonshedding surface in wet or humid conditions.Biofilms are complex and dynamic populations of microorganisms that adhere to each other and to a substrate (including the skin and hairs in and around the pinnae and ear canals). The microbial cells are embedded within a slimy extracellular matrix composed of a complex array of polysaccharides, proteins, lipids, and DNA. Cells in a biofilm are physiologically distinct from planktonic cells (ie, living in a liquid medium) of the same organism. Subpopulations may differentiate to specialize in motility, matrix production, nutrient sharing, and sporulation. This can make biofilms highly persistent and (from a microbial point of view) successful strategies. Almost all microbes can form biofilms; they are most common with Pseudomonas spp in otitis but can be seen with Staphylococcus spp, other bacteria, and Malassezia yeasts.
生物膜很常见，在湿或潮湿的情况下，它们几乎会在任何不脱落的表面形成。生物膜是一种复杂的、动态的微生物群，它们相互粘附并附着在基质上(包括耳廓和耳道内及其周围的皮肤和毛发上)。微生物细胞被嵌在由多糖、蛋白质、脂质和DNA组成的复杂阵列的黏液状细胞外基质中。生物膜中的细胞在生理学上不同于其浮游态细胞(即生活在液体培养基中)。亚群可以分化为专门的运动、基质产生、营养共享和形成孢子。这可以使生物膜高度持久性和(从微生物的角度)成功的策略。几乎所有的微生物都能形成生物膜;在耳炎中最常见的是假单胞菌属，但也可见于葡萄球菌属、其他细菌和马拉色菌属。
The diagnosis of biofilms is usually straightforward; they have a characteristic clinical feel and appearance (see Table 6 and Figure 7). On modified Wright-Giemsa stained cytology (ie, rapid in-clinic stains), they form a fine pink-cerise veil or net-like material embedding the neutrophils and organisms (Figure 8), although periodic acid Schiff can be used as a more specific stain. However, optimizing culture techniques to identify biofilm-forming ability from clinical samples would help clinicians when planning treatment in cases where the biofilm is not clinically or cytologically obvious.
生物膜的诊断通常很简单;它们具有特征性的临床感觉和外观(见表6和图7)。在改良的瑞-姬姆萨染色细胞学(即快速临床染色)中，它们形成一个细的粉红-鲜红色纱布或网状物质，包入中性粒细胞和微生物(图8)，但PAS染色可以作为更特异的染色剂。然而，优化培养技术以确定临床样本的生物膜形成能力，将有助于临床医师在生物膜临床或细胞学不明显的情况下制定治疗计划。
Biofilms have a profound impact on treatment. Once established, they enable bacteria to persistently colonize tissues, medical equipment (including otoscopes), and environments. They are sheltered from environmental factors, cleaning, disinfection, antimicrobials, and innate and adaptive immunity. Exposure to sublethal antimicrobial concentrations within biofilms selects for antimicrobial and disinfectant resistance, which can then spread within and between populations. Some organisms within biofilms may also have altered physiological susceptibility to antimicrobials (ie, persister cells that show reversible antimicrobial tolerance). This allows biofilm-associated infections to rapidly recrudesce following treatment. It is therefore essential that all the biofilm is removed from the ear canals, pinnae, hairs, and other body sites (eg, lip folds and body folds) at the start of treatment.
生物膜对治疗有深远的影响。一旦建立，细菌就能在组织、医疗设备(包括耳镜)和环境中持续定殖。他们不受环境因素、清洁、消毒、抗微生物药物以及先天和适应性免疫的影响。暴露于生物膜内的亚致死抗菌浓度可选择抗微生物和消毒剂耐药性，然后可在群体内和群体间传播。生物膜内的一些微生物也可能改变了对抗生素的生理敏感性(即表现出可逆性抗菌素耐受的存留细胞)。这使得生物膜相关感染在治疗后迅速复发。因此，在治疗开始时，必须清除耳道、耳廓、毛发和其他机体部位(如唇褶和体褶)的所有生物膜。
N-acetyl cysteine (NAC) can damage biofilms, lower the MIC, and enhance the efficacy of systemic antibiotics. It therefore possible that NAC and similar antibiofilm compounds may aid the treatment of biofilm-associated infections in animals. A commercially available Tris EDTA-NAC solution may facilitate removal and treatment of biofilms in ear canals, although time should be left between this and topical antibiotics as an in vitro study found most interactions between NAC and enrofloxacin or gentamicin were indifferent to antagonistic. Other compounds with potential anti-biofilm and antimicrobial activity include chlorhexidine, polihexanide, hypochlorous acid, and Tris-EDTA.
n-乙酰半胱氨酸(NAC)可破坏生物膜，降低MIC，增强全身性抗生素的疗效。因此，NAC和类似的抗生物膜化合物可能有助于治疗动物生物膜相关感染。商品化的Tris EDTA-NAC溶液可促进耳道生物膜的清除和治疗，但由于体外研究发现，NAC与恩诺沙星或庆大霉素之间的大多数相互作用不存在拮抗作用，因此与外用抗生素之间应留出一定的时间。其他具有潜在抗生物膜和抗菌活性的化合物包括氯己定、聚己胺、次氯酸和Tris-EDTA。
Reversing Chronic Pathological Changes
逆转慢性病理改变
As well as eliminating infection, the aim of the induction phase of treatment is to reverse the acquired pathological changes and restore the normal ear canal structure and function. A good outcome cannot be achieved without this. Once in remission, long-term therapy is needed to maintain the improvement and prevent relapse.
在消除感染的同时，诱导期治疗的目的是逆转获得性病理改变，恢复正常耳道结构和功能。没有这一点，就不可能取得好的结果。一旦缓解，需要长期治疗以维持改善并防止复发。
This requires broad-spectrum anti-inflammatory treatment, which in effect means topical or systemic glucocorticoids. These must be given to remission before tapering (Table 8); this may take 2 to 3 weeks and will induce steroid-associated adverse effects. Ciclosporin does not appear to be effective at reversing inflammatory changes but may be helpful for long-term maintenance. Semi-broad (eg, oclacitinib)- or narrow (eg, lokivetmab and antihistamines)- spectrum agents have limited efficacy in otitis.
这就需要进行广谱抗炎治疗，实际上就是外用或全身使用糖皮质激素。这些药物必须在减量前达到缓解(表8);这可能需要2-3周，并会引起与类固醇相关的不良反应。环孢素似乎不能有效逆转炎症变化，但可能有助于长期维持。半广谱(如奥拉替尼)或窄谱(如洛基维特单抗和抗组胺药)药物对耳炎的疗效有限。
Avoiding Pain and Aversion
避免痛苦和厌恶
Otitis is often painful, especially where there is severe inflammation, Pseudomonas spp infections, and/or ulceration. Without adequate analgesia, dogs quickly become aversive to ear cleaning and topical treatment. This greatly restricts effective options for managing immediate otitis as well as long-term maintenance treatment. The need for analgesia must be assessed and addressed in each case. More recently, we have seen increased numbers of dogs that are resistant to topical treatment from the outset. This may be related to a lack of socialization, veterinary experiences, and training during the 2020 COVID-19 pandemic.
耳炎通常疼痛，尤其是有严重炎症、假单胞菌感染和/或溃疡的地方。如果没有足够的镇痛，犬会很快对洗耳液和外部治疗产生厌恶。这极大地限制了即时耳炎管理和长期维持治疗的有效选择。必须评估并解决每个病例对镇痛的需求。最近，我们看到越来越多的犬从一开始就对外部治疗有抵抗。这可能与在2020年COVID-19大流行期间缺乏社交、兽医经验和培训有关。
Topical leave-in products (florfenicol/terbinafine/ mometasone furoate, florfenicol/terbinafine/ betamethasone) can maintain therapeutically effective concentrations in the ear canals for up to 35 days. The products can have a significant impact on quality of life by giving a “treatment holiday.” However, they are potentially ototoxic, can trigger inflammation in the conjunctiva, and have been associated with neurogenic keratoconjunctivitis sicca. In addition, florfenicol is not effective against Pseudomonas spp, and therefore, these products are not appropriate for most cases of suppurative otitis.
外用长效产品(氟苯尼考/特比萘芬/糠酸莫米松，氟苯尼考/特比萘芬/倍他米松)可在耳道内维持治疗有效浓度长达35天。这些产品可以给人们一个“治疗假期”，从而对生活质量产生重大影响。然而，它们可能有耳毒性，可诱发结膜炎，并与神经源性干燥性角结膜炎相关。此外，氟苯尼考对假单胞菌无效，因此这些产品不适用于大多数化脓性耳炎病例。
Clinicians have a role in helping owners train their dogs to accept topical treatment. This can start in early life by advising new owners to build in ear manipulation into play. Clinics can demonstrate safe and effective ear cleaning and therapy techniques through training, social media, and websites. Retraining dogs to accept topical therapy is possible with a slow and gradual approach to desensitization, analgesia, anti-anxiety medication, and high-value rewards.
临床医生可以帮助主人训练他们的犬接受外部治疗。这可以从早期开始，建议新主人在游戏中加入耳道操作。诊所可以通过培训、社交媒体和网站展示安全有效的耳部清洁和治疗技术。通过脱敏、镇痛、抗焦虑药物和高价值奖励等缓慢而渐进的方法，可以重新训练犬接受外部治疗。
Future Anti-Inflammatory and Antimicrobial Treatment Options
未来的抗炎和抗菌治疗方案
There are several new approaches to managing infections and inflammation in skin and ears under development. Early results (especially in vitro studies) are encouraging, although more clinical trials are needed to confirm efficacy.
目前正在开发几种治疗皮肤和耳道感染和炎症的新方法。早期的结果(尤其是体外研究)令人鼓舞，但需要更多的临床试验来证实疗效。
New technologies that may modulate inflammation and infection in the skin and ears include photobiomodulation (low-level laser therapy, ultraviolet, and blue or red light with or without the prior application of photoactivated chemicals) and cold plasma.
可能调节皮肤和耳道炎症和感染的新技术包括光生物调节(低水平激光治疗、紫外线、蓝光或红光，事先或不事先应用光活化化学物质)和冷等离子体。
Bacteriophages are highly species-specific antibacterial viruses. First discovered in the late 19th century, they were used as antibacterial agents in the early to mid-20th century before being superseded by antibiotics. With the advent of MDR, there is now renewed interest in bacteriophage therapy. In a pilot study, specific anti-Pseudomonas phages cleared MDR ear infections in 10 dogs. Biobanking phages with known efficacy will help reduce the delay in isolating phages specific to each infection. Another approach would be to isolate and replicate broad-spectrum antibacterial phage proteins (bacteriolysins) in a stable formulation for immediate use.
噬菌体是一种具有高度物种特异性的抗菌病毒。它们于19世纪末首次被发现，在20世纪早期至中期被用作抗菌剂，之后被抗生素取代。随着多重耐药的出现，噬菌体疗法重新引起了人们的兴趣。在一项初步研究中，特异性抗假单胞菌噬菌体清除了10只犬的MDR耳感染。已知效力的生物库噬菌体将有助于减少分离针对每种感染的特异性噬菌体的延迟。另一种方法是在稳定的配方中分离和复制广谱抗菌噬菌体蛋白(溶菌素)，以供立即使用。
Other novel antimicrobial compounds include various essential plant oils and extracts, manuka honey, antimicrobial peptides, lactoferricin, and Tris-EDTA/monensin. Early studies show good in vitro efficacy, although this can be more varied in the presence of mature biofilms. Nevertheless, clinical studies have been limited and efficacy is more variable.
其他新型抗菌化合物包括各种植物精油和提取物、麦卢卡蜂蜜、抗菌肽、乳铁蛋白和Tris-EDTA/莫能菌素。早期的研究显示出良好的体外疗效，但在成熟生物膜的存在下，这可能会更加多样化。然而，临床研究有限，疗效变化较大。
These approaches could become new and effective treatments for otitis. However, clinical studies have been limited by low numbers of dogs, inconsistent outcome data, and a tendency to focus on one aspect of the otitis (for example, steroids were not used in clinical trials of antimicrobial peptide and honey-containing products). Further studies are clearly required, but it is unlikely that any one of these novel options will become a “cure” for otitis. Instead, they are likely to become further options to include in integrated treatment programs that address the primary triggers, predisposing factors, perpetuating changes, and secondary infections in each case.
这些方法可能成为治疗耳炎新的有效方法。然而，临床研究受到以下因素的限制:犬的数量少、结果数据不一致，以及倾向于只关注耳炎的一个方面(例如，类固醇在抗菌肽和含蜂蜜产品的临床试验中未使用)。显然需要进一步的研究，但这些新方案中的任何一个都不太可能成为耳炎的“治愈”方法。相反，它们可能成为综合治疗计划的进一步选择，以解决每个病例的原发因素、易感因素、持久改变和继发感染。
Summary of Treatment Recommendations for Otitis Externa
外耳炎治疗建议总结
Recurrent ear infections in dogs are always secondary. Topical treatment for each flare will be successful in the short term, but repeated cycles of inflammation and infection will lead to chronic inflammatory changes, pain and aversion, and AMR. These will make the flares more frequent and harder to control. Eventually, the changes will be irreversible and the dog will need a TECA/LBO or ablative CO2 or diode laser surgery; clinicians should reflect on the fact that most TECA/LBO or laser surgery is avoidable.
犬复发性耳部感染通常是继发的。外部治疗每次急性发病在短期内是成功的，但炎症和感染的反复循环会导致慢性炎症改变，疼痛和厌恶，以及AMR。这将使急性发病更加频繁，更难控制。最终，这些变化将是不可逆转的，犬将需要TECA/LBO或CO2消融或二极管激光手术;临床医生应该反思这样一个事实，即大多数TECA/LBO或激光手术是可以避免的。
To achieve a good long-term outcome it is essential that all the underlying factors in each case are diagnosed and managed. This means that the primary condition must be diagnosed and managed, predisposing risks identified and (as far as possible) corrected, and perpetuating factors reversed.
为了获得良好的长期结果，必须对每个病例的所有潜在因素进行诊断和管理。这意味着必须对原发疾病进行诊断和管理，确定并(尽可能地)纠正易感风险，并逆转持久因素。
Treatment must be planned in the 2 following phases:
治疗计划必须分以下两个阶段进行:
• Induction to get the ears in remission: this may involve cleaning the ear with an appropriate technique and product, antimicrobial therapy, and topical or systemic glucocorticoids.
•诱导耳部缓解:这可能包括使用适当的技术和产品清洁耳道，抗菌治疗，外部或全身糖皮质激素。
• Long-term maintenance therapy to prevent relapses: this may involve regular ear cleaning and topical glucocorticoids alongside therapy appropriate to the primary and predisposing problems in each case.
•长期维持治疗以防止复发:这可能包括定期耳道清洁和外用糖皮质激素以及适合每个病例的原发和易感问题的治疗。
A better understanding of the triggers for recurrent otitis in dogs will help clinicians plan effective management regimens that will make a huge difference to the quality of life of their patients and their owners. For example, in 1 study of 59 dogs with recurrent Malassezia yeast otitis unresponsive to primary care, 91% of the affected ears responded to a single ear flush that was followed up with a holistic integrated management plan.
更好地了解犬复发性耳炎的诱因将有助于临床医生制定有效的管理方案，这将对患犬及其主人的生活质量产生巨大影响。例如，在一项对59只对初级保健无效的复发性马拉色酵母菌耳炎的犬进行的研究中，91%的患耳对单次耳部冲洗有效，随后进行了整体综合管理计划。
Figure 5—End-stage otitis in an American Cocker Spaniel with multiple ceruminous polyps completely occluding the ear canals. These glandular and cystic changes are less responsive to glucocorticoid therapy than the epidermal/dermal hyperplasia seen in other breeds.
图5:美国可卡犬终末期耳炎，多个耵聍息肉完全堵塞耳道。与其他品种的表皮/真皮增生相比，这些腺体和囊性变化对糖皮质激素治疗的反应较差。
Figure 6—Early perpetuating changes of nodular hyperplasia giving the ear canal a thickened “cobblestone” appearance. This is the early warning that the dog has started to develop chronic otitis and should prompt treatment to reverse the changes.
图6早期持久性改变结节性增生，耳道呈增厚的“鹅卵石样”外观。这是犬已经开始发展慢性耳炎的早期警告，应该及时治疗以扭转改变。
Figure 7—Biofilm from a dog with otitis; note the characteristic dark color with the tenacious and slimy texture.
图7 -一只耳炎患犬的生物膜;请注意其特有的深色，质地坚韧而粘稠。
Figure 8—Cytology of a biofilm with neutrophils and rod bacteria embedded in a net- or veil-like cerise substance (Rapi-Diff 2 stain and 100X magnification).
图8一个生物膜细胞学检查，中性粒细胞和杆菌包在网状或面纱状鲜红色物质中的(Rapi-Diff 2染色和100倍放大)。
Table 1—Primary factors in otitis externa.
表1外耳炎的主要因素。
分组 |
举例 |
耳炎发病率 |
过敏反应 |
特应性皮炎/食物诱发的特应性皮炎 皮肤食物副反应 接触性过敏或刺激反应 |
常见 不常见 不常见；;通常是局部药物和清洁剂 |
寄生虫 |
耳螨 蠕形螨 |
常见（特别是年轻犬） 不常见；通常伴有全身性发病 |
占位性病变 |
耵聍腺瘤/腺癌、浆细胞瘤等肿瘤 炎性息肉 |
老年犬常见 不常见至罕见 |
内分泌病 |
肾上腺皮质亢进，甲状腺功能减退，和高雌激素(支持细胞瘤) |
不常见 |
免疫介导 |
医源性(如糖皮质激素治疗、化疗等) 原发性免疫缺陷病 |
不常见 罕见 |
其他 |
异物（例：草芒） 获得性瘢痕组织和狭窄 |
常见 不常见 |
先天性 |
耳道狭窄或闭锁 |
罕见 |
Table 2—Predisposing factors in otitis externa.
表2外耳炎的易感因素。
分类 |
因素 |
解剖与构象 |
耳廓和/或耳道多毛
耳廓下垂
耵聍腺的密度增加和生理改变(尤其是耵聍腺)
美国,西班牙猎犬)
耳道狭窄(中国沙皮)或阻塞 |
生活方式及管理 |
游泳
过度清洁(浸湿、浸渍、耳道深层物质嵌塞、医源性损伤)
例行拔耳毛
湿热环境 |
Table 3—Comparison of diagnostic imaging techniques in otitis externa.
表3外耳炎诊断影像技术比较。
参数 |
X光 |
CT |
MRI |
价格 |
低 |
中等 |
高 |
时间 |
中等 |
快 |
长 |
限制需求 |
镇静或麻醉 |
镇静或麻醉 |
麻醉 |
摆位难度 |
+++ |
+ |
+ |
特异性 |
良好 |
良好 |
良好（软组织）-不佳（骨结构） |
敏感性 |
不佳 |
良好 |
良好（软组织）-不佳（骨结构） |
Table 4—Topical antibiotics in otic preparations listed according to the European Medicines Agency categorization of antibiotics for animal use.
表4 -根据欧洲药品管理局动物用抗生素分类列出的耳药中的外部抗生素。
分类 |
抗生素 |
A：避免 |
未许可 |
B：限制 |
氟喹诺酮 多粘菌素B |
C：谨慎 |
氨基糖苷 氟苯尼考 |
D：审慎 |
夫西地酸 |
Table 5—General principles of treatment for Pseudomonas spp otitis.
表5假单胞菌性耳炎的一般治疗原则。
Table 6—Otic discharges and ear cleaners.
表6 -耳分泌物和洗耳液。
分泌物/洗耳液 |
描述 |
颜色 |
深棕色 |
浅棕至灰 |
浅棕至黄 |
黄至绿 |
深绿至黑 |
粘稠度 |
腊状和粘附 |
腊状和皮脂溢 |
皮脂溢至化脓 |
化脓 |
又厚又黏 |
相关疾病 |
耵聍性耳炎 |
马拉色酵母菌 |
葡萄球菌属 |
假单胞菌属 |
生物膜 |
需要铈的溶解和溶剂活性 |
+++ |
++ |
+ |
- |
50mg/mlTris-EDTA或2%NAC |
表面活性剂和洗涤剂冲洗 |
- |
+ |
++ |
+++ |
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Table 7—Ear cleaning techniques.
表7 -耳道清洁技术。
技术 |
手动清洁 |
洗耳球 |
耳道冲洗 |
优点 |
简单 宠主可操作 无需镇静和麻醉 |
更有力度和有效 动物意识清醒 |
彻底清洁耳道(包括水平耳道和鼓膜)的唯一方法 |
缺点 |
疗效有限 |
风险增加（包括鼓膜破裂） |
需要全身麻醉(额外的局部神经阻滞可能有用) |
适应症 |
常规家庭清洁 |
临床清洁 |
深部耳道冲洗和清洁 |
表8慢性病理性炎症改变的治疗方案。
变化 |
治疗方法 |
说明 |
早期变化:耵聍增生伴狭窄;耳道仍然柔韧可动 |
外用二酯(如氢化可的松，乙酰酸)或传统糖皮质激素(如糠酸莫米松，地塞米松，曲安奈德，倍他米松) |
每天缓解，然后逐渐减少维持
二酯糖皮质激素因其更好的安全性而首选用于维持治疗 |
轻度改变:耵聍增生伴早期狭窄和柔韧性丧失;耳道仍可活动 |
外用传统糖皮质激素 强的松/强的松或甲基强的松 |
每天缓解，然后逐渐减少 1(强的松龙)/0.8(甲基强的松龙)mg/kg/d至缓解，然后逐渐减少 |
中度变化:表皮/真皮增生，部分狭窄，柔韧性降低;还可以做耳镜检查，耳道还能活动 |
强的松/强的松或甲基强的松 |
1(强的松龙)/0.8(甲基强的松龙)mg/kg/d至缓解，然后逐渐减少 |
严重的改变:表皮/真皮增生，几乎完全狭窄，柔韧性受限，活动能力降低 |
曲安奈德 地塞米松 静脉注射糖皮质激素(曲安奈德40 mg/mL或地塞米松3 mg/mL) |
0.8 mg/kg/d至缓解，然后逐渐减少 0.14 mg/kg/d至缓解，然后逐渐减少 在水平耳道和垂直耳道注射三次0.05 ml |
终末期中耳炎:完全狭窄伴固定耳道 |
外侧大球截骨术全耳道消融(TECA/LBO) 二氧化碳或二极管激光手术 |
在大多数情况下，这些技术是可以避免的 激光手术保留耳道，但可用性可能有限 |
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a Use of potent traditional glucocorticoids (eg, triamcinolone and dexamethasone) has a greater risk of adverse effects, and (wherever possible) daily treatment should be for a maximum of 14 days after which the frequency should be tapered. a使用传统的强效糖皮质激素(如曲安奈德和地塞米松)有更大的副反应风险，(如有可能)每日治疗应最多持续14天，之后频率应逐渐减少。
b Laser surgery can also be used in the severe changes category.b激光手术也可用于严重病变。
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|Archiver|手机版|小黑屋|宠医帮
( 京ICP备2022012070号-2 ) 
发表于 2023-6-28 23:39:19
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