快速生长的分枝杆菌引起犬皮下组织和皮肤感染-2004

王帆

Infections of the subcutis and skin of dogs caused by rapidly growing mycobacteria

快速生长的分枝杆菌引起犬皮下组织和皮肤感染-2004

翻译：李慧晓

Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were examined over 17 years. Dogs were two to 15 years; five were male, four were female. All were obese or in good condition. Antecedent injury, typically a dog bite or vehicular trauma, could be identified in some patients, while one bitch had hyperadrenocorticism. Infections involved different locations, although the cervicothoracic region, dorsum or flank were most often affected. Patients were systemically well, apart from one dog with pyrexia and two with pain or lameness. Cytology demonstrated pyogranulomatous inflammation, but in only one case was it possible to see acid-fast bacilli (AFB) in smears. Histology demonstrated chronic active pyogranulomatous panniculitis and dermatitis; AFB could be detected in only four specimens. Culture of aspirates or resected tissues demonstrated RGM in all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium fortuitum group isolates. Resection of infected tissues, perioperative injectable antimicrobials and long courses of oral antimicrobials chosen according to susceptibility data generally effected a cure, although some cases recurred.

9只由于快速生长分枝杆菌(RGM)感染导致的脂膜炎患犬检查超过17年。犬的年龄是2到15岁。五只雄性，四只雌性。这些患犬要么肥胖，要么健康状况良好。一些患犬以前有过创伤，典型的是犬咬伤或车祸，而一只母犬有肾上腺皮质机能亢进。感染涉及不同部位，但颈胸区、背侧或协腹侧是最常见的患病部位。除1只犬发热、2只犬疼痛或跛行外，其余全身健康。细胞学显示脓性肉芽肿性炎症反应，但仅有一例涂片可见抗酸杆菌(AFB)。组织学表现为慢性活跃性脓性肉芽肿性脂膜炎和皮炎。AFB仅在4份样本中检出。所有病例的抽吸物或切除组织培养均显示RGM，包括6株耻垢分枝杆菌组和3株偶发分枝杆菌组分离株。切除感染组织、围手术期注射抗菌剂以及根据药敏资料选择长期口服抗菌剂，一般可治愈，但有些病例复发。

INTRODUCTION

介绍

Mycobacteria are aerobic, non-motile Gram-positive rods that have a cell wall rich in mycolic acids and mycosides as their distinguishing feature . These lipids are responsible for many characteristic features of the genus, including the retention of carbol fuchsin stain following acid and/or alcohol treatment (acid-fastness), the ability to withstand drying, and the capacity to survive and multiply within phagocytes . A feature of mycobacterial disease is the associated inflammatory response, which is generally granulomatous or pyogranulomatous, as might be expected for an infection in which antigen-specific cell-mediated immunity is required to activate macrophages to deal effectively with bacteria capable of intracellular survival. Although pyogranulomatous inflammation is a feature of disease associated with saprophytic mycobacteria , a similar picture may be evident in infections associated with other bacteria that have high lipid contents (for example, Corynebacterium, Nocardia and Rhodococcus species), fungal infections and foreign body reactions.

分枝杆菌是需氧、非运动革兰氏阳性杆菌，细胞壁富含肌分枝菌酸和分枝杆菌糖脂，是其显著特点。这些脂质引起该菌属的许多特征，包括在酸和/或酒精处理后石炭酸复红染色的保留（耐酸性）、耐干燥能力以及在吞噬细胞内生存和增殖的能力。分枝杆菌病的特征之一是相关的炎症反应，通常为肉芽肿性或脓性肉芽肿性，感染如预期的一样，需要抗原特异性细胞介导的免疫来激活巨噬细胞以有效处理能够在细胞内存活的细菌。虽然脓性肉芽肿性炎症是腐生分枝杆菌相关疾病的特征，但类似情况也可能发生在与其他高脂含量细菌（例如棒状杆菌、诺卡氏菌和红球菌属）相关的感染、真菌感染和异物反应中。

Rapidly growing mycobacteria (RGM) are a heterogeneous group of organisms that produce visible colonies on synthetic media within seven days when cultured at 24 to 45° C . They are distributed ubiquitously in nature and can be commonly isolated from soil, dirt and bodies of water, including tap water .Bacteria in this group include the Mycobacterium fortuitum group (including Mycobacterium fortuitum, Mycobacterium peregrinum and the third biovariant complex), the Mycobacterium chelonae/abscessus group (including Mycobacterium chelonae and Mycobacterium abscessus), the Mycobacterium smegmatis group (including Mycobacterium smegmatis sensu stricto,Mycobacterium goodii and Mycobacterium wolinskyi), and a variety of other nonpigmented RGM including Mycobacterium phlei and Mycobacterium thermoresistibile. The taxonomy of this group has recently been revised.

快速生长分枝杆菌(RGM)是一组异质性微生物，当在24-45 ℃下培养时，在合成培养基上7天内产生可见菌落。它们在自然界中广泛分布，通常可从土壤、污垢和水中分离，包括自来水。该组细菌包括偶发分枝杆菌组（包括偶发分枝杆菌、外来分枝杆菌和第3种生物变种复合群）、龟分枝杆菌/脓肿分枝杆菌组（包括龟分枝杆菌和脓肿分枝杆菌）、耻垢分枝杆菌组（包括狭义耻垢分枝杆菌、古地分枝杆菌和沃林斯基分枝杆菌）以及多种其他无色素RGM，包括草分枝杆菌和耐热分枝杆菌。最近对该组的分类方法进行了修订。

In both humans and animals, RGM are strongly linked with localised infections of immunocompetent hosts. This is because they are well adapted to a saprophytic existence and inherently have low virulence for mammals. Thus, they do not produce disease unless a breakdown in normal defence barriers allows them to enter a favourable tissue environment. Once introduced, RGM are generally constrained by a vigorous immunological response which may or may not eradicate them from the host’stissues, but is effective enough to prevent haematogenous or lymphatic spread.Disseminated disease may be caused by RGM, but only in immunocompromised individuals.

在人类和动物中，RGM与具有免疫活性的宿主的局部感染密切相关。这是因为它们很好地适应了腐生生物的存在，并且本身对哺乳动物的毒性较低。因此，它们不会产生疾病，除非正常的防御屏障被破坏，允许它们进入一个有利的组织环境。一旦引入，RGM通常会受到强烈的免疫反应的限制，这种反应可能会也可能不会将它们从宿主组织中根除，但足以有效地防止血液或淋巴扩散。RGM可能引起弥散性疾病，但仅见于免疫功能低下者。

RGM produce three different syndromes in dogs: mycobacterial panniculitis, lobar pneumonia and disseminated infections.Mycobacterial panniculitis refers to a clinical syndrome characterised by chronic infection of the subcutis and skin with RGM. This condition is quite common in Australian cats and a series of 49 cases has been reported. In contrast, far fewer canine cases have been documented and the authors were able to locate only 10 cases (all from the USA) in electronic databases.

RGM在犬上会产生三种不同的综合征：分枝杆菌性脂膜炎、大叶性肺炎和弥散性感染。分枝杆菌脂膜炎是指RGM引起的以皮下组织和皮肤慢性感染为特征的临床综合征。这种情况在澳大利亚猫中相当常见，已经有一份49例病例的病例报告。相比之下，记录在案的犬类病例要少得多，作者只在电子数据库中找到10例病例（均来自美国）。

RGM may replicate in tissues if introduced through a breach in the skin in sufficient numbers and under suitable conditions. This typically follows penetrating injury, especially when the wound is contaminated by dirt or soil. Preference of RGM for fat is a key factor in the pathogenesis and results in the tendency for disease to occur in obese individuals and in tissues rich in lipids, such as the subcutaneous panniculus and especially the inguinal fat pad of cats. Experimental infections cannot be induced readily in subjects that do not have appreciable subcutaneous fat .Likewise, experimental infection of ovine mammary glands requires instillation of oil in addition to organisms to induce mastitis.

如果在合适的条件下通过皮肤裂口引入足够数量的RGM，则其可以在组织中复制。这通常发生在贯穿性损伤之后，尤其是当伤口被污物或土壤污染时。RGM对脂肪的偏好是发病机制的关键因素，导致疾病倾向肥胖个体和富含脂质组织（如皮下脂膜，尤其是猫的腹股沟脂肪垫）。实验性感染不易在没有明显脂肪的实验动物中诱发。同样，实验性感染绵羊乳腺诱发乳腺炎时，除注入微生物外，还需要滴入油。

The same phenomenon accounts for situations where these organisms give rise to human infections; for example, in athletes injected with drugs in oil-based vehicles from contaminated vials, as a complication of lipoid pneumonia and following augmentation mammoplasty, liposuction and sternotomy. Initial reports suggested that mycobacterial panniculitis was more common in warm humid climates, but recent studies have recorded disease in temperate regions including Canada, Finland  and Germany. Also, causal organisms have been cultivated from Japanese soil samples . In Australia, M smegmatis accounts for the majority of feline cases, whereas it is a much less common cause of equivalent infections in humans, in which M fortuitum infections predominate.

这些微生物引起人类感染的情况也是如此。例如，健康的人注射了被污染药瓶中的油性载体的药物，是导致隆胸术、抽脂术和胸骨切开术的术后并发症脂质性肺炎的原因。最初报告表明，分枝杆菌脂膜炎在温暖潮湿的气候中更常见，但最近的研究记录了温带地区的疾病，包括加拿大，芬兰和德国。此外，还从日本土壤样本中培养了致病微生物。在澳大利亚，耻垢分枝杆菌占猫病例的大多数，而在人类中，它是一个不太常见的感染病因，偶发分枝杆菌占大多数。

In cats, infections generally start in the inguinal region, usually following environmental contamination of cat-fight injuries, such as raking wounds inflicted by the hind claws. The infection may spread to contiguous subcutaneous tissues of the ventral and lateral abdominal wall and perineum. Penetrating injuries caused by sticks and metallic objects, as well as vehicular trauma, may cause these infections, as might contaminated bite injuries.Feline infections are characterised by an indurated subcutaneous lesion adherent to the overlying skin, that becomes denuded of hair and develops numerous punctate fistulae which discharge a watery exudate. Fistulae are intermingled with focal purple depressions that correspond to thinning of the epidermis over an accumulation of pus. If the lesion is confused with an anaerobic cat bite abscess, treatment, consisting of lancing, drainage and oral lactams,is typically followed by dehiscence and development of a non-healing wound.

在猫中，感染通常从腹股沟区域开始，通常是在猫打架受伤的环境污染之后，例如后爪造成的抓伤。感染可扩散至腹壁、腹壁外侧及会阴的邻近皮下组织。由木棒和金属物体引起的穿透伤以及车祸创伤可能引起这些感染，咬伤被污染也可能引起这些感染。猫感染的特征为一种皮肤硬化病变上边附着着皮肤、无毛发、形成许多点状瘘管，排出水样渗出物。瘘管与局灶性紫色凹陷混杂在一起，与聚集的脓液导致表皮变薄有关。如果病变与厌氧性猫咬伤脓肿混淆，治疗方案包括切开、引流和口服内酰胺类抗生素，通常发展成伤口裂开并形成不愈合伤口。

Some cats with severe infections develop constitutional signs, yet others remain well despite extensive disease.Occasional cats develop the hypercalcaemia of granulomatous disease, although this is rarely, if ever, symptomatic. The problem usually remains localised to the skin and subcutis. Adjacent structures such as the abdominal wall can be affected eventually, but spread to internal organs or lymph nodes is very rare.Similar infections have been reported in captive marsupial carnivores.

一些严重感染的猫出现体质性症状，但还有一些猫尽管出现广泛性疾病但依然健康。偶见患猫发生肉芽肿性疾病的高钙血症，但罕有症状。问题通常局限于皮肤和皮下组织。邻近结构（如腹壁）最终可能会受到影响，但扩散到内脏器官或淋巴结的情况非常罕见。在圈养的有袋类食肉动物中也报告了类似感染报道。

Few reports document the clinical course, diagnosis and management of dogs with mycobacterial panniculitis, although a recent study identified key clinicopathological findings in such cases. This paper presents clinical and laboratory findings in nine dogs with RGM infections and compares the syndrome in canine and feline patients.

很少有报告记录分枝杆菌脂膜炎患犬的临床病程、诊断和治疗管理，但最近的一项研究确定了此类病例中的关键临床病理学结果。本文介绍了9只RGM感染患犬的临床和实验室检查结果，并比较了犬和猫的综合征。

MATERIAL AND METHODS

材料和方法

Nine dogs were included in the study (Table 1), representing cases which had been encountered between 1985 and 2002. Private practitioners had initially managed the dogs. In five cases (four from Perth and one from Sydney), the animal was subsequently examined and treated at a university teaching hospital. The remaining cases were managed entirely by the primary clinician, but with laboratory support and/or advice from one of the authors.

本研究纳入了9只犬（表1），为1985年至2002年期间遇到的病例。私人医生最初对犬进行了管理。有5例病例（4例来自珀斯，1例来自悉尼）中，随后在大学教学医院对动物进行检查和治疗。其余病例完全由首诊临床医生管理，但有实验室支持和/或其中一位作者的建议。

Dogs ranged in age from two to 15 years. Five dogs were male and four were female. A variety of breeds was represented including purebreeds and crossbreeds, large and small dogs, and dogs with a variety of body conformations. Four were said to be in good condition, four were considered obese and one had pituitary-dependent hyperadrenocorticism. In cases where a good history was available, an antecedent penetrating injury had been witnessed, typically a dog bite (four cases) or vehicular trauma (one case).Wounds were situated in a variety of locations, although the cervicothoracic region, dorsum or flank were most commonly affected. Lesions consisted of nodules, multiple draining sinus tracts and subcutaneous swelling or oedema (Figs 1 to 5). Most animals were systemically well, apart from one animal that had pyrexia and two that experienced pain or lameness.

犬的年龄范围为2-15岁。5只犬为雄性，4只为雌性。品种多样，包括纯种犬和杂交犬、大型犬和小型犬以及具有各种身体特征的犬。4只患犬体况良好，4只患犬肥胖，1只患犬有垂体依赖性肾上腺皮质功能亢进。有详细病史的病例中，曾观察到先前的穿透伤，通常为犬咬伤（4例）或车祸创伤（1例）。虽然颈胸区域、背部或侧腹最常患病，但伤口位于多个部位。病变包括结节、多处窦道和皮下肿胀或水肿（图1-5）。除一只动物出现发热和两只动物出现疼痛或跛行外，大多数动物全身状况良好。

FIG 1. A five-year-old spayed female keeshond (case 4) with Mycobacterium smegmatis infection of the subcutis of the lateral thoracic region. Note the subcutaneous oedema (prominent ventrally) and draining sinus tract.Ultrasonography was used to locate and aspirate a specimen of purulent fluid for cytological examination and culture.

图1.一例5岁已绝育雌性荷兰毛狮犬（病例4）侧胸区皮下耻垢分枝杆菌感染。注意皮下水肿（腹侧突出）和窦道。采用超声对脓性液体标本进行定位和抽吸，进行细胞学检查和培养。

FIG 2. An eight-year-old, neutered male Labrador (case 5) with extensive Mycobacterium smegmatis infection of the withers and lateral thorax after radical resection of infected subcutaneous adipose tissue.(A) Right-sided view. (B) Left-sided view.

图2.一例8岁、去势的雄性拉布拉多犬（病例5），在感染的皮下脂肪组织根治性切除术后，躯干和胸侧出现大面积的耻垢分枝杆菌感染。(A)右侧图。(B)左侧图。

FIG 3. A 15-year-old, male Australian cattle dog (case 6) with Mycobacterium fortuitum infection of the right thoracic wall, after en bloc resection of infected tissues and placement of a latex drain.

图3.，一只15岁雄性澳大利亚牧牛犬（病例6）右侧胸壁偶发分枝杆菌感染，整块切除感染组织并放置乳胶引流管。

FIG 4. A four-year-old, Staffordshire bull terrier bitch (case 3) with Mycobacterium smegmatis infection of the left lateral cervical region.(A) Attempted surgical debridement by the referring veterinarian resulted in wound dehiscence.(B) Close-up view.

图4.一只四岁雌性的斯塔福斗牛㹴（病例3），左侧颈区有耻垢分枝杆菌感染。（A）转诊兽医尝试手术清创导致伤口开裂。(B)放大图像。

FIG 5. A 10-year-old, male terrier crossbreed (case 7) with Mycobacterium fortuitum infection of the left lateral thigh region.Note the numerous punctate, draining sinus tracts surrounding the primary lesion.

图5.一例10岁雄性杂交㹴犬（病例7），左大腿外侧区有偶发分枝杆菌感染。注意原发病灶周围存在许多点状窦道。

Specimen collection, cytology and histology

标本采集、细胞学和组织学

The diagnosis was made by aspirating pus or obtaining deep tissue samples for cytology, histology or culture. In cats, pus obtained from aspirates of affected tissues through intact skin (following disinfection of the skin surface) provided the best laboratory specimens.Such a sample was obtained using ultrasound guidance in one of the nine dogs.However, samples collected by private practitioners were typically large, surgically resected tissue specimens.

通过抽吸脓液或获取深部组织样本进行细胞学、组织学或培养做出诊断。在猫中，通过完整皮肤（皮肤表面消毒后）抽吸患病部位组织获得的脓液，是最佳的实验室样本。在超声引导下，从9只犬中的1只获得该样本。但是，首诊医生采集的样本通常为大型、手术切除组织标本。

Portions of these biopsies were triturated in brain heart infusion broth or similar liquid media using a sterile pestle and mortar. Smears of the resulting homogenate or aspirates from infected tissues were stained using Diff-Quik, Burke’s modification of the Gram stain and a modified acid-fast procedure (decolourising with 5 percent sulphuric acid for three to five minutes). Histological sections were embedded in paraffin, processed routinely and stained using haematoxylin and eosin, Brown and Brenn (in some cases) and Ziehl-Neelsen stains, and were evaluated using light microscopy.

使用无菌研棒和研钵在脑心浸液肉汤或类似液体介质中研碎部分活检样本。使用Diff-Quik、Burke改良的革兰氏染色和改良的抗酸程序（用5%硫酸脱色3-5分钟）对感染组织的匀浆或抽吸物涂片进行染色。将组织切片包埋在石蜡中，进行常规处理，并使用苏木精和伊红、Brown和Brenn染色（在某些病例中），以及抗酸染色进行染色，并使用光学显微镜进行判读。

Bacteriology and strain identification

细菌及菌种鉴定

Tissue homogenates and aspirates of pus were streaked onto duplicate 5 percent sheep blood agar plates and a mycobacterial medium, such as Lowenstein-Jensen medium or 1 percent Ogawa egg yolk medium, and incubated aerobically at 37°C and 25°C, respectively. In cases where samples were submitted to a private laboratory, specimens were sometimes inoculated into the appropriate BACTEC bottle and cultured at 37°C in a BACTEC 9000 automated liquid culture system (Becton Dickinson Biosciences). Blood agar plates were incubated for seven to 10 days, while solid media were incubated for up to six weeks.

将组织匀浆和脓液抽吸物划线重复接种到5%羊血琼脂平板和分枝杆菌培养基上，如罗氏培养基或1%小川蛋黄培养基，分别在37℃和25℃有氧培养。样本提交至私人实验室的病例，有时将样本接种至合适的快速培养瓶中，并在37℃下于BACTEC 9000自动液体培养系统中培养。血液琼脂平板培养7-10天，而固体培养基培养长达6周。

Where only contaminated specimens were available, tissue homogenates were sometimes treated with 4 per cent sodium hydroxide followed by neutralisation with dilute hydrochloric acid, prior to inoculation onto media. Another method used to selectively separate RGM from contaminant flora, such as Staphylococcus intermedius, was primary isolation around a β-lactam susceptibility disc, applied to the plate after inoculation.

当只有污染的样本时，在接种培养基前，会将组织匀浆用4%氢氧化钠处理，随后用稀盐酸中和。用于从污染菌群（如中间型葡萄球菌）中选择性分离RGM的另一种方法是在β-内酰胺药敏纸片周围进行初步分离，接种后应用于平板。

Strain identification was confirmed at a mycobacteria reference laboratory (either Queensland Health Pathology Services or Western Australian Centre for Pathology and Medical Research), following primary isolation. Identification took into account some or all of the following phenotypic features: organism morphology in ZiehlNeelsen-stained smears of growth taken from Lowenstein-Jensen medium; colonial morphology (rough or smooth); pigmentation in the dark and light; degree of acid-fastness; rate of growth at room temperature and 37°C; ability to grow at 42°C and 52°C; arylsulphatase activity; iron uptake; p-amino salicylic acid degradation; nitrate reduction; β-galactosidase activity; acid production from carbohydrates (glucose, inositol and mannitol); utilisation of compounds (glucose, fructose, inositol, mannitol and citrate) as the sole carbon source; tolerance to 5 per cent sodium chloride in Lowenstein-Jensen medium; and susceptibility to polymyxin B, trimethoprim and tobramycin . In two cases, the isolates (M goodii and M fortuitum) were further identified using direct sequence determination of 16S rRNA gene fragments amplified using PCR.

初步分离后，在分枝杆菌参考实验室（昆士兰健康病理学服务或澳大利亚西部病理学和医学研究中心）确认菌株鉴定。鉴定考虑了以下部分或全部表型特征：从罗氏培养基获取的抗酸染色生长涂片中的微生物形态；菌落形态（粗糙或光滑）；在黑暗和光照条件下的色素沉着；耐酸程度；在室温和37℃下的生长速率；在42℃和52℃下生长的能力；芳香硫酸酯酶活性；铁吸收；对氨基水杨酸降解；硝酸盐还原；β-半乳糖苷酶活性；碳水化合物（葡萄糖、肌醇和甘露醇）产酸；化合物的利用（葡萄糖、果糖、肌醇、甘露醇和柠檬酸盐）作为唯一碳源；对在罗氏培养基中5%氯化钠的耐受性；对多粘菌素B、甲氧苄啶和妥布霉素的敏感性。在2例病例中，使用PCR扩增的16srRNA基因片段的直接序列测定，进一步鉴定分离株（古地分枝杆菌和偶发分枝杆菌）。

Isolates were included as being in the M fortuitum group if they grew in less than seven days at 28°C and 37°C; produced rough, non-pigmented colonies; had a positive three-day arylsulphatase reaction; were positive for iron uptake; reduced nitrate; and showed susceptibility to polymyxin B but not trimethoprim.M fortuitum group isolates were divided into species according to their utilisation of mannitol, inositol and citrate as sole sources of carbon for growth. The M fortuitum group was differentiated from the M chelonae/abscessus group based on biochemical differences and susceptibility to polymyxin B (M fortuitum group sensitive, M chelonae/abscessus group resistant).

如果菌株在28℃和37℃下7天内生长；产生粗糙无色素菌落；3天芳香硫酸酯酶反应呈阳性；铁摄取呈阳性；硝酸盐减少；对多粘菌素B敏感，但对甲氧苄啶不敏感，则将其纳入偶发分枝杆菌组。根据偶发分枝杆菌组分离物利用甘露醇、肌醇和柠檬酸盐作为生长唯一碳源的种类进行分类。根据生化差异和对多粘菌素B的敏感性（偶发分枝杆菌组敏感，螯合分枝杆菌/脓肿分枝杆菌组耐药），区分偶发分枝杆菌组与螯合分枝杆菌/脓肿分枝杆菌组。

Isolates were included in the M smegmatis group if they grew well at 43°C but not at 52°C, were positive for iron uptake and had a negative three-day arylsulphatase reaction. Colonies of M smegmatis obtained from clinical material were typically smooth and not immediately pigmented, although a late-developing yellow-to-orange pigmentation was seen in many isolates. M smegmatis isolates generally had a characteristic antibiogram, with susceptibility to a wide range of agents including ethambutol, tetracyclines, sulphamethoxazole, trimethoprim, gentamicin and fluoroquinolones, but often not clarithromycin.

如果分离株在43℃生长良好，而在52℃生长不佳，铁吸收阳性，且三天芳基硫酸酯酶反应阴性，则将其纳入耻垢分枝杆菌组。从临床样本获得的耻垢分枝杆菌菌落通常光滑，不会立即有色素，但在许多分离株中观察到晚期发生的黄色至橙色色素沉着。耻垢分枝杆菌分离株通常具有特征性抗菌谱，对多种药物敏感，包括乙胺丁醇、四环素类、磺胺甲恶唑、甲氧苄胺嘧啶、庆大霉素和氟喹诺酮类，但通常对克拉霉素不敏感。

Antimicrobial susceptibility testing

抗生素药敏试验

Antimicrobial susceptibility of clinical isolates was determined using a disc diffusion method. Typically isolates were tested against discs containing amoxycillin/clavulanic acid (20/10;30 µg), trimethoprim/sulphamethoxazole (1·25/23·75; 25 µg), clarithromycin (30 µg), tobramycin (10 µg), amikacin (30 µg), gentamicin (10 µg), ciprofloxacin (5 µg), enrofloxacin (5 µg),cefoxitin (30 µg), minocycline (30 µg), doxycycline (30 µg), sulphamethoxazole (250 µg), polymyxin B (300 µg) and trimethoprim (5 µg). Some antibiotics were included to determine therapeutic agents, while others were used to provide phenotypic information for taxonomic purposes.

使用纸片扩散法测定临床分离株的抗菌敏感性。对含有阿莫西林/克拉维酸（20/10；30µg）、甲氧苄啶/磺胺甲恶唑（1·25/23·75；25µg）、克拉霉素（30µg）、妥布霉素（10µg）、阿米卡星（30µg）、庆大霉素（10µg）、环丙沙星（5µg）、恩诺沙星（5µg）、头孢西丁（30µg）、米诺环素（30µg）、多西环素（30µg）、磺胺甲恶唑（250µg）的纸片检测典型分离株。多粘菌素B（300µg）和甲氧苄啶（5µg）。包括一些抗生素以确定治疗药物，而其他抗生素用于提供表型信息以供分类之用。

Suspensions of each organism in saline or nutrient broth were inoculated onto Mueller Hinton II agar (BBL) supplemented with a 1:10 dilution of oleic acid, albumin, dextrose, catalase (OAFC; Becton Dickinson) or sensitivity agar (Isosensitest agar; Oxoid) and incubated at 37°C.Results were recorded after incubation for 48 and 72 hours.

将每种微生物在生理盐水或营养肉汤中的混悬液接种到添加了油酸、白蛋白、葡萄糖、过氧化氢酶或敏感性琼脂，并在37°C下培养。培养48和72小时后记录结果。

Because of the long period over which cases were accrued, the range and number of agents tested was not consistent. The minimum inhibitory concentration (MIC) for clarithromycin was determined to guide therapy in one dog (case 7) using the E-test method (AB Biodisk).

由于病例累积周期较长，试验药物的范围和数量不一致。使用E-试验方法（AB Biodisk）测定克拉霉素的最小抑菌浓度（MIC），以指导一只犬治疗（病例7）。

RESULTS

结果

A mycobacterial aetiology was not initially suspected in any animal, with veterinarians considering other explanations for lesions, such as a foreign body reaction to plant material (grass awns, sticks). Most cases were managed by attempted surgical excision, suturing and a routine course of antimicrobial therapy.This approach led to persistence of clinical signs, wound breakdown or primary intention healing followed some time later by recrudescent infection. A definitive  diagnosis was obtained subsequently by either demonstration of acid-fast bacilli in ultrasound-guided needle aspirates (one case), Ziehl-Neelsen-stained histological sections (four cases), or by positive culture from aspirates (one case) or tissue specimens collected at surgery (nine cases).

所有动物最初都不怀疑病因是分枝杆菌，兽医考虑了对病变的其他解释，例如植物异物反应（草芒、木棍）。大多数病例通过手术切除、缝合和抗菌治疗的常规抗菌治疗进行管理。这种方法导致临床症状持续存在、伤口破裂或最初一期愈合，一段时间后出现复发感染。随后通过超声引导穿刺采样（1例）证实抗酸杆菌、经抗酸染色的组织切片（4例）或穿刺物（1例）或手术时采集的组织样本（9例）培养阳性来确诊。

Cytological evaluation invariably demonstrated pyogranulomatous inflammation, but only in one case was it possible to visualise acid-fast bacilli in smears. In this instance, an exhaustive search was required and organisms were only weakly acid-fast. Histological findings were similar in all cases, consisting of chronic active pyogranulomatous panniculitis and dermatitis. Acid-fast bacilli were generally hard or impossible to find in ZiehlNeelsen-stained sections. They were visualised in four of eight cases where tissue was available for histological examination and were situated in cleared spaces, likely to be lipid vacuoles (Fig 6), or intracellularly within macrophages.

细胞学判读总是显示脓性肉芽肿性炎症，但只有1例涂片中可见抗酸杆菌。在这种情况下，需要进行全面检索，微生物仅为弱抗酸菌。所有病例的组织学结果相似，包括慢性活跃性脓性肉芽肿性脂膜炎和皮炎。在抗酸染色切片中，抗酸杆菌通常很难或不可能发现。在8例组织学检查中，只有4例能观察到，位于空白区域，可能是位于脂质空白区（图6），或巨噬细胞内。

Moderate to heavy growth of pinpoint, smooth or rough, non-haemolytic colonies was usually observed after two to three days’ incubation on sheep blood agar at 37°C. Of the nine isolates, six were of the M smegmatis group (including one M goodii strain) and three were of the M fortuitum group. M smegmatis group isolates accounted for all four cases from Western Australia and two of the five cases from New South Wales.Susceptibility data for the isolates are shown in Table 2.

37°C羊血琼脂上培养2-3天后，通常观察到针尖状、平滑或粗糙、非溶血性菌落的中度至重度生长。9个分离株中，6个为耻垢分枝杆菌组（包括1个古地分枝杆菌菌株），3个为偶发分枝杆菌组。在西澳大利亚州的4例病例和新南威尔士5例病例中的2例中，存在耻垢分枝杆菌组分离株。分离株的药敏数据见表2   

Definitive treatment was attempted in each dog and typically consisted of radical resection of all grossly affected tissues, suturing of the resulting defect and administration of antimicrobials, based on susceptibility testing, for periods ranging from six weeks to six months. Given the extent and severity of the disease process in most of the dogs, it was considered that adequate levels of antimicrobials were unlikely to be achieved throughout all involved tissues without surgical resection.Thus, the best chance for a successful longterm outcome was to remove as much infected tissue as possible following preliminary antimicrobial therapy, and target residual foci of infection with high concentrations of antibiotics during and after surgery.

尝试对每只犬进行根治性治疗，通常包括彻底切除所有严重感染的组织、缝合伤口并根据药敏试验给予抗菌剂，时间从6周到6个月不等。考虑到大多数犬疾病进程的情况和严重程度，如果不进行手术切除，不太可能在所有感染组织中达到足够水平的抗菌素，因此，获得成功的长期结果的最佳机会是在初步抗菌治疗后尽可能多地去除感染组织，以及在术中和术后高浓度抗生素靶向治疗残留感染病灶。

The experience and expertise of the surgeon varied from case to case, as did the choice of pre-, peri- and postoperative antimicrobials. Typically, a very large portion (up to 10*12 cm) of infected subcutis required excision and the resulting tissue deficits necessitated the use of latex or closed suction drains to evacuate the remaining dead space. Complex reconstructive techniques were not required because of the availability of mobile healthy skin nearby. A variety of antimicrobials were used according to factors such as time of treatment (fluoroquinolones were not available in Australia in 1985), clinicians’ preference, perceived response to therapy, susceptibility data and cost considerations. A large number of combinations were used, with different drugs being used sequentially and sometimes simultaneously. Antimicrobials available in injectable formulations (gentamicin, trimethoprim/sulphamethoxazole and enrofloxacin) tended to be used perioperatively and in the early postoperative period, while long-term therapy utilised agents that could be given orally.

外科医生的经验和专业知识因病例而异，术前、围手术期和术后抗菌剂的选择也各不相同。通常，需要切除很大一部分（高达10*12 cm）的感染皮下组织，产生的组织缺损必须使用乳胶或封闭抽吸引流管以排空剩余的死腔。不需要复杂的皮瓣重建技术，因为附近有可移动的健康皮肤。根据治疗时间（1985年在澳大利亚无法获得氟喹诺酮类药物）、临床医生的偏好、对治疗的感知反应、药敏数据和成本考虑等因素使用了多种抗菌剂。使用了大量的联合用药，不同的药物依次使用，有时同时使用。可注射制剂中的可用抗菌剂（庆大霉素、甲氧苄啶/磺胺甲恶唑和恩诺沙星）倾向于在围手术期和术后早期使用，而长期治疗使用可口服给药的药物。

Most patients responded favourably to therapy. Dogs were generally uncomfortable for several days following surgery, often requiring pain relief using either opiates or non-steroidal anti-inflammatory agents. Wounds generally healed by first or, occasionally, second intention without untoward sequelae. Six cases were thought to be cured, one recurred and two were lost to follow-up.

大多数患犬对治疗反应良好。术后数天犬通常会感到不适，通常需要使用阿片类或非甾体抗炎药缓解疼痛。伤口通常一期愈合或偶尔二期愈合，无不良后遗症。认为6例治愈，1例复发，2例失访。

FIG 6. Ziehl-Neelsen-stained histological section of a biopsy specimen from a dog

with mycobacterial panniculitis due to Mycobacterium smegmatis. Note the cluster

of acid-fast bacilli in an extracellular cleared space, which is likely to be a lipid vacuole.

图6。一例由耻垢分枝杆菌引起的犬脂膜炎活检样本的抗酸染色组织学切片。注意在细胞外清除的间隙中有一团抗酸杆菌，这很可能是脂质空白区。

FIG 7. Ultrasonogram of a focus of suppurative inflammation in the subcutis of the forearm of one of the authors (R. M.) caused by a Mycobacterium marinum infection.

Ultrasound-guided needle aspirates provided an ideal specimen for culture.

图7.作者之一（R. M.）的前臂皮下组织化脓性炎症病灶超声图（由海洋分枝杆菌感染引起）。

超声引导穿刺为培养提供了理想的样本。

DISCUSSION

讨论

This paper records the largest series of dogs with mycobacterial panniculitis reported so far in the literature. Most previous reports document one or two cases, with the exception of Jang and Hirsh’s study that included five dogs with RGM panniculitis. Taken together with the present cases, it is clear that mycobacterial panniculitis in dogs has a number of characteristic features. There are similarities with, but also differences from, the equivalent feline condition.

本文记录了文献中迄今为止报告的最大的分枝杆菌脂膜炎患犬病例系列。大多数既往报告记录了1例或2例，Jang和Hirsh的研究除外，其包括5只RGM脂膜炎患犬。结合当前病例，犬的分枝杆菌脂膜炎明显具有许多特征性表现。与猫科动物相似疾病存在相似之处，但也存在差异。

Clinicians should suspect RGM infections when presented with patients with chronic non-healing wounds which are unresponsive to drainage and conventional antibiotic therapy. As Jang and Hirsh have suggested, the difficulty in making a diagnosis in a timely manner is probably responsible, in part, for the chronicity, severity and refractoriness of these infections.

当患犬对引流和常规抗生素治疗无效，出现慢性不愈合伤口时，临床医生应怀疑RGM感染。正如Jang和Hirsh提出的，很可能难以及时做出诊断，部分原因是这些感染的长期性、严重程度和难治性。

Lesions typically consist of firm to fluctuant subcutaneous swellings or nodules,which ulcerate, drain and spread centrifugally, with the development of new ‘satellite’ lesions at the edges of older lesions.Some cases behave differently and instead spread widely through the subcutis to produce multifocal lesions through the subcutaneous panniculus (case 9). Lesions tend to be neither painful nor pruritic, and are generally located in regions subjected to bite wounds or injections, such as the neck, shoulders, flank or dorsum. There is typically a prior history of penetrating injury; for example, a bite wound or veterinary intervention such as injection (especially from multi-use vials) or previous surgery.

病变通常包括坚硬至波动的皮下肿胀或结节、溃疡、窦道和中间向周围扩散，在陈旧病变的边缘出现新的“卫星”病变。有些病例表现不同，而是通过皮下组织大面积扩散，通过皮下脂膜产生多灶性病变（病例9）。病变部位一般不疼痛也不瘙痒，通常位于咬伤或注射的部位，如颈部、肩部、侧腹或背部。通常有贯穿伤既往史；例如咬伤或兽医干预，如注射（尤其是多次使用药瓶）或既往手术史。

Microscopic examination shows pyogranulomatous inflammation with neutrophils gathered in small foci (microabscesses) or forming thin rims around cleared spaces (lipid vacuoles), granulomatous inflammation including giant cells and granulation tissue beneath the inflamed area. Cytological examination shows that organisms stain poorly or not at all with Gram or a Romanowsky-type stain such as DiffQuik, and even modified acidfast stains are unreliable at demonstrating acid-fast bacilli in smears.

显微镜检查显示脓性肉芽肿性炎症，中性粒细胞聚集在小病灶（微脓肿）中或在空隙（脂质空白区）周围形成薄边界，肉芽肿性炎症包括炎症区域下方的巨细胞和肉芽组织。细胞学检查显示，微生物用革兰氏染色或罗曼诺夫斯基染色（如DiffQuik）较差或完全不染色，甚至改良抗酸染色也不能可靠地显示涂片中的抗酸杆菌。

Speckled structures or non-staining ‘ghosts’, corresponding to poorly staining or non-staining bacilli, have been observed in smears stained with Romanowsky-type stains , but are much harder to appreciate than in cases with Mycobacterium avium infections or leproid granulomas. Similarly, acid-fast bacilli can be difficult or impossible to find in paraffin-embedded histological specimens, even using stains such as ZiehlNeelsen, Fite’s or Kinyoun’s, and it has been theorised that some aspect of fixation affects organisms’ ability to take up or retain the stain. Thus, early diagnosis is best achieved by culture of appropriate specimens.

在罗曼诺夫斯基染色的涂片中观察到斑点结构或不着色“影”，相当于染色差或不着色的杆菌，但比鸟分枝杆菌感染或类麻风病肉芽肿更难判断。同样，即使使用抗酸染色、Fite染色或抗酸金永染色，在石蜡包埋的组织学样本中也很难或不可能找到抗酸杆菌，理论上，固定的某些方面会影响微生物吸收或保留染色剂的能力。因此，早期诊断最好通过合适的样本培养实现。

Experience with feline cases suggests that needle aspirates of fluid from intact nodules or subcutaneous swellings provide the best specimens with which to make a diagnosis. Obviously, intact overlying skin should be disinfected prior to obtaining the aspirate to preclude the isolation of saprophytic bacteria residing on the skin surface. It may be necessary to relocate the needle in the subcutaneous space while applying constant negative pressure until a pocket of purulent material is encountered. Alternatively, high definition ultrasonography can be used to find locations suitable for aspiration (Fig 7).

在猫病例中的经验表明，从完整结节或皮下肿胀部位抽吸液体是进行诊断的最佳样本。显然，应在采集抽吸物之前对覆盖完整的皮肤进行消毒，以避免分离出残留在皮肤表面的腐生细菌。可能需要将针头重新放置在皮下空间内，同时施加恒定的负压，直到遇到充满脓汁的腔。或者，可以使用高清晰度超声检查来查找适合抽吸的位置（图7）。

Purulent fluid should be submitted to the laboratory for culture or inoculated immediately into a commercially prepared  mycobacteria culture bottle. As positive primary culture takes two to four days, with an additional two- to four-day period for susceptibility testing, the initial choice of antimicrobials must be guided by retrospective susceptibility data.

脓液应提交至实验室进行培养或立即接种到商业化分枝杆菌培养瓶。由于阳性原代培养需要2-4天，另外2-4天的时间进行药敏试验，抗菌剂的初始选择必须根据回顾性药敏数据进行指导。

In Australia, M smegmatis and M fortuitum group infections are encountered in canine patients with mycobacterial panniculitis, whereas in southern USA M fortuitum and M chelonae/abscessus infections predominate, accounting for seven and four, respectively, of the 11 cases recorded in the literature. The over-representation of M smegmatis cases in Australia is statistically significant (P<0·01; Fisher’s exact test). The reasons why M smegmatis group infections are common in Australian dogs while M chelonae/abscessus infections are rare are unclear, although differences in soil types and climate are likely to play a part. Based on the Australian data presented here, the breakdown of M smegmatis and M fortuitum group infections is similar in dogs and cats in a given geographical area.

在澳大利亚，分枝杆菌脂膜炎患犬中出现耻垢分枝杆菌和偶发分枝杆菌组感染，而在美国南部，偶发分枝杆菌和龟/脓肿分枝杆菌感染占优势，文献记录的11例病例中分别占7例和4例。澳大利亚耻垢分枝杆菌病例的过度代表具有统计学意义（P<0.01；Fisher精确检验）。为什么在澳大利亚犬中常见耻垢分枝杆菌组感染，而龟/脓肿分枝杆菌感染罕见，原因尚不清楚，但土壤类型和气候差异可能起一定作用。基于此处提供的澳大利亚数据，在给定地理区域内，犬和猫中的耻垢分枝杆菌和偶发分枝杆菌感染分类相似。

It is hard to make definitive treatment recommendations based on the management of only a limited number of cases.Thus, advice is drawn in part from experience gained treating feline and human patients with RGM infections, as well as findings reported here and in previous publications. When a tentative diagnosis of an RGM infection is made, it is desirable to immediately start treatment with an agent likely to be effective against the causal organism. As M smegmatis and M fortuitum infections both occur in Australia, doxycycline (5 to 10 mg/kg, orally twice daily) or a fluoroquinolone (for example, enrofloxacin, 5 to 15 mg/kg, daily) are cost-effective empirical choices.In the USA, clarithromycin (10 to 15 mg/kg, orally twice daily) is probably the drug of choice because M fortuitum and M chelonae isolates are predominant.

仅根据有限数量的病例管理很难提出明确的治疗建议。因此，部分治疗建议来自RGM感染的猫和人的经验，以及本文和既往文献中报告的结果。在初步诊断为RGM感染时，最好立即开始使用可能对病原微生物有效的药物进行治疗。由于耻垢分枝杆菌和偶发分枝杆菌感染均发生在澳大利亚，多西环素（5-10 mg/kg，口服，每日两次）或氟喹诺酮（例如恩诺沙星，5-15 mg/kg，每日一次）是经济有效的经验性选择。在美国，克拉霉素（10-15 mg/kg，口服，每日2次）很可能是首选药物，因为偶发分枝杆菌和龟分枝杆菌分离株是主要的分离株。

Recent recommendations for treating RGM infections in human patients emphasise that mycobacteria may develop resistance to quinolones during therapy.Thus, it may be prudent to use quinolones strategically after surgical debulking or to only use them in conjunction with another agent, thereby reducing the likelihood of resistance developing. Such considerations are less applicable to doxycycline or clarithromycin as mutational resistance to these drugs is less likely to develop. For this reason, many veterinary dermatologists in Australia use combination therapy with doxycycline and a quinolone from the outset, as in case 9.

近期关于治疗人类患者RGM感染的建议强调，治疗期间分枝杆菌可能对喹诺酮类产生耐药性。因此，在手术减积后策略上谨慎使用喹诺酮类药物或仅将其与另一种药物联合使用，从而降低发生耐药性的可能性。这些考虑不适用于多西环素或克拉霉素，因为这些药物不太可能发生突变耐药性。因此，澳大利亚许多兽医皮肤病学家从一开始就使用多西环素与喹诺酮联合治疗，如病例9。

Once susceptibility data become available, the optimal drug(s) are selected. The response in vivo to an agent known to be effective in vitro can then be assessed. In general, it is necessary to use as high a dose as possible of antimicrobials when treating these infections, because affected subcutaneous tissues are not well perfused and considerable diffusion barriers hinder antibiotics reaching organisms in fat, despite adequate blood levels. Treatment should commence using standard dose rates. Subsequently, the dosage should be increased over several weeks until adverse side effects (inappetence and vomiting) suggest the need for a slight dose reduction, and/or a favourable clinical response is observed.

一旦获得药敏数据，就可以选择最佳药物。然后可评估对已知在体外有效的药物的体内反应。一般来说，治疗这些感染时必须使用尽可能高剂量的抗菌剂，因为感染的皮下组织灌注不良，虽然血液浓度足够，但是大量的弥散障碍会阻碍抗生素到达脂肪中的微生物。应采用标准剂量率开始治疗。随后，应在数周内增加剂量，直至有不良副作用（食欲不振和呕吐）表明需要轻微降低剂量和/或观察到有效的临床反应。

Some cases treated in a preliminary fashion using orally administered agents respond to such an extent that surgery becomes unnecessary. These cases can thus be cured using medicinal therapy alone, although treatment for up to 12 months may be needed. In general, cases that resolve without additional surgery involve a lesser depth of tissues than cases that later require operative debridement. However, many cases are so severe that only limited improvement can be achieved with antimicrobial therapy alone and surgery is required to effect a cure.Because it is not possible to predict which cases will require debridement, the authors’ current recommendation is to start therapy using one or a combination of agents known to be effective in the laboratory, increase drug dosages progressively and then reassess the patient periodically to decide if continued improvement is occurring or if surgery is necessary. Preliminary antimicrobial therapy is beneficial because it reduces the quantity of tissue requiring resection and minimises the possibility of wound dehiscence.

一些使用口服药物初步治疗的病例的有效程度，达到了无需手术治疗。因此，虽然可能需要长达12个月的治疗，但这些病例可以单独使用药物治疗治愈。一般而言，在不需要手术的情况下痊愈的病例所涉及的组织深度要小于后来需要手术清创的病例。但是，许多病例的病情非常严重，仅能通过抗菌治疗获得有限的改善，需要手术才能治愈。由于无法预测哪些病例需要清创，作者目前的建议是使用一种或联合已知在实验室有效的药物开始治疗，逐渐增加药物剂量，然后定期重新评估病患，以确定是否继续改善或是否有必要进行手术。初步抗菌治疗是有益的，因为它减少了需要切除的组织量，并将伤口裂开的可能性降至最低。

If surgery is required, a drug which is effective against the causal strain and that can be given by injection, such as gentamicin, should be administered intraoperatively (2 mg/kg every eight hours or 6 mg/kg every 24 hours, intravenously or subcutaneously) and in the early postoperative period (typically for three to five days). Gentamicin is a good choice because it is bactericidal, inexpensive and displays good activity against likely mycobacterial isolates. Amikacin would be equally or more effective, although substantially more expensive. The critical surgical consideration is to remove as much abnormal subcutaneous tissue as possible, typically necessitating the resection of very large portions of infected adipose tissue. Affected tissues should ideally be removed en bloc but in many cases there is such extensive panniculitis that this is not feasible. Advanced cases with extensive lesions ideally require the skill of an experienced surgeon to reconstruct the resulting tissue deficit without undue tension, although this requirement is less than that for the equivalent surgery in cats. The large amount of dead space created by debridement requires judicious use of latex or closed suction drains for several days postoperatively。

如果需要手术，应该在术中和术后早期（通常是3-5天），给予能够有效对抗致病菌株并且可以通过注射给药的药物，例如庆大霉素（每8小时一次，2 mg/kg，或者每24小时一次，6 mg/kg，静脉注射或者皮下注射）。庆大霉素是一种良好的选择，因为其具有杀菌性，价格低廉，并且对可能的分枝杆菌分离株表现出良好的活性。阿米卡星同样有效或更有效，但价格明显更高。关键的手术考虑是切除尽可能多的异常皮下组织，通常必须切除大部分感染的脂肪组织。理想情况下应将患病组织整块切除，但在许多病例中存在如此大面积的脂膜炎，以至于不可行。在理想情况下，具有大面积病变的晚期病例需要有经验的外科医师在不过度张力的情况下重建导致的组织缺损的技术，但该要求低于在猫中进行的等同手术。清创术造成的大量死腔需要在术后几天合理地使用乳胶或封闭抽吸的引流管。

Following surgery, drugs of greatest theoretical efficacy are used as soon as oral dosing is possible so that residual bacteria at the wound margins are targeted by high levels of effective agent(s), thereby facilitating primary intention healing. M smegmatis group isolates are susceptible to a wide range of agents well suited to treating chronic infections, whereas M fortuitum isolates generally demonstrate resistance to one or several drugs. The authors have no experience with M chelonae isolates, but human data indicates they are resistant to all common antimicrobials available for oral dosing, apart from clarithromycin. Because of cost considerations and other practicalities, the choice generally comes down to one or a combination of a fluoroquinolone, doxycycline or clarithromycin.

在手术后，尽快使用理论上最有效的药物口服给药，以使伤口边缘的残留细菌成为高水平有效药物的靶标，从而促进一期愈合。耻垢分枝杆菌组分离株对广泛的适合治疗慢性感染的药物敏感，而偶发分枝杆菌分离株通常表现出对一种或几种药物的耐药性。作者没有关于龟分枝杆菌分离株的经验，但是人体数据表明，除克拉霉素外，对所有常见口服抗菌剂均耐药。出于成本考虑和其他实践，通常选择氟喹诺酮类、多西环素或克拉霉素的一种或联合治疗。

In Australia, fluoroquinolones (ciprofloxacin, enrofloxacin, marbofloxacin and orbifloxacin) and doxycycline are considered the agents of choice because M smegmatis and M fortuitum strains cause most infections. Quinolones are bactericidal, penetrate well into tissues (including fat) and are concentrated in polymorphs and macrophages, but are contraindicated in young growing animals.

在澳大利亚，氟喹诺酮类药物（环丙沙星、恩诺沙星、马波沙星和奥比沙星）和多西环素被认为是首选药物，因为耻垢分枝杆菌和偶发分枝杆菌菌株引起大多数感染。喹诺酮类药物具有杀菌性，能够很好地渗透至组织（包括脂肪）中，并且能够集中分布在多形态和巨噬细胞中，但是禁忌用于生长期幼龄动物。

Doxycycline has a cost advantage over quinolones, is equally well suited to longterm oral therapy and has similar efficacy, in the authors’ experience. Doxycycline monohydrate is the tetracycline of choice in small animal patients, being well tolerated orally, present in a readily available form (Vibravet tablets; Pfizer Australia, Doximed; Ratiopharm) and having good lipid solubility. The monohydrate salt is not freely available in the USA, which is problematic because other doxycycline salts are more irritant, causing vomiting through irritation of the stomach or, worse, ulceration of the oesophagus. For this reason, doxycycline should be either given immediately before meals or be followed by a small amount of liquid by mouth.

根据作者的经验，多西环素与喹诺酮类药物相比具有成本优势，同样适合长期口服治疗，疗效相似。在小动物病患中，多西环素是首选的四环素，口服耐受良好，以容易获得的形式存在，脂溶性良好。一水合物盐在美国不可自由获得，这是一个问题，因为其他多西环素盐刺激性更强，通过胃刺激引起呕吐或更严重的食管溃疡。因此，多西环素应在餐前立即给药或随后口服少量液体。

Clarithromycin is a macrolide derivative with an extended spectrum of activity and prolonged pharmacokinetics. It has proved extremely useful in treating mycobacterial infections in humans, including those caused by RGM, and in dogs with refractory leproid granulomas. Its major disadvantages are high cost (an issue in large canine patients) and a high proportion of M smegmatis group  isolates’ resistance to the drug.

克拉霉素是一种大环内酯衍生物，具有广谱活性和延长的药代动力学。已证实其在治疗人类分枝杆菌感染（包括RGM引起的感染）和难治性麻风肉芽肿犬中极为有效。其主要缺点是成本高（大型患犬中的一个问题）和耻垢分枝杆菌群比例高分离株的耐药性。

The propensity of mycobacteria to develop resistance during treatment is well known, although this phenomenon is less problematic for RGM than Mycobacterium tuberculosis, M avium and Mycobacterium leprae. Development of resistance is most likely for quinolones, probably because of selection of pre-existing mutants. There is insufficient information to recommend routine combination therapy, although such therapy may be prudent. The possibility of resistance developing during quinolone therapy should be considered in cases where an initially favourable response is not sustained.

分枝杆菌在治疗期间产生耐药性的倾向是众所周知的，但这一现象对RGM的影响小于结核分枝杆菌、鸟分枝杆菌和麻风分枝杆菌。喹诺酮类药物最有可能产生耐药性，这可能是由于选择了既存的突变体。尚无足够的信息推荐常规联合治疗，但这种治疗可能是谨慎的。在最初未见持续有效的情况下，应考虑喹诺酮治疗期间发生耐药的可能性。

The total duration of therapy should be in the order of three to six months. Drugs should be administered for at least one to two months after affected tissues look and feel completely normal.Some cases in this series treated in the 1980s were given sulphamethoxazole/ trimethoprim combinations or tetracyclines, but the human and veterinary literature suggests that these agents are less effective than contemporary agents. In occasional refractory cases, clofazimine, cefoxitin or amikacin may be used for monotherapy or in conjunction with other agents. Cefoxitin and amikacin can only be given by injection.Several new oral agents for treating refractory RGM infections have become available recently, including gatifloxacin and linezolid. Gatifloxacin has greater efficacy than older quinolones against M fortuitum and M chelonae isolates. Although these agents hold great promise for refractory mycobacterial infections, their high cost currently precludes routine use, especially in large dogs.

总治疗持续时间应该是3-6个月。感染组织外观和感觉完全正常后，应至少给药1-2个月。20世纪80年代治疗的这个病例系列中有些病例给予了磺胺甲恶唑/甲氧苄啶复方制剂或四环素类，但是人类和兽医文献提示这些药物的疗效低于当前的药物。偶有难治性病例，可单独使用氯法齐明、头孢西丁或阿米卡星或与其他药物联合使用。头孢西丁和阿米卡星只能注射给药。近期出现了几种治疗难治性RGM感染的新型口服药物，包括加替沙星和利奈唑胺。加替沙星对偶发分枝杆菌和龟分枝杆菌分离株的疗效大于较老的喹诺酮类药物。虽然这些药物对难治性分枝杆菌感染有很大的希望，但其高成本目前阻碍了常规使用，尤其是在大型犬中。

Conclusions

结论

Canine mycobacterial panniculitis is an eminently treatable disease. Diagnosis is not problematic, so long as the practitioner maintains a high index of suspicion for a mycobacterial aetiology. The prognosis is favourable, even in cases with severe chronic disease. Treatment involves long courses of antimicrobials chosen on the basis of susceptibility testing, often combined with extensive debridement and wound reconstruction. The comment by Fox and others that ‘in general, the clinical response in dogs is more rapid and more complete than in cats’ could well be true. Importantly, the routine prophylactic use of doxycycline following treatment of penetrating injuries in obese dogs (and cats) may help prevent the development of these infections.

犬分枝杆菌脂膜炎是一种明显可治疗的疾病。只要执业兽医师对分枝杆菌病因学保持高度怀疑指数，则诊断不存在问题。预后良好，即使是重度慢性疾病患犬。治疗涉及根据药敏试验选择的长疗程抗菌药物，通常联合大面积清创和伤口重建。Fox和其他人的评论“通常而言，犬的临床反应比猫更快、更完整”很可能是正确的。重要的是，在治疗肥胖犬（和猫）的贯穿伤后常规预防性使用多西环素可能有助于预防发生这些感染。

Addendum

附录

Since submission of this paper, the authors have been involved with two further canine patients with subcutaneous RGM infections. Both dogs were from New South Wales (Sydney and Coffs Harbour), and both were M smegmatis group infections.

自本文提交以来，作者又涉及了两名皮下RGM感染的犬患者。两只犬均来自新南威尔士（悉尼和科夫港），均为耻垢分枝杆菌组感染。

红蓝紫

bateer578

高级感满满

Ryohei

廊坊永鑫罗玄

学习了。

杨爱娟

学习

zhangenzyme