引言
类鼻疽由需氧、革兰阴性、运动性杆菌——伯克霍尔德菌(Burkholderia pseudomallei)引起,该菌为环境腐生菌,大多数病例发生于热带和亚热带地区。尽管最常在东南亚和澳大利亚北部报道,1–5 该菌被认为至少在45个国家呈地方性流行,美国疾病控制与预防中心(CDC;6-8)最近宣布美国墨西哥湾沿岸地区为地方性流行区。目前存在关于该菌可能传播至当前非地方性流行地区的担忧,非地方性流行地区的散发性报告提示可能已经存在未被识别的疫源地。2 随着人类和动物在全球范围内的流动日益增加,存在感染宠物从地方性流行地区输入非地方性流行地区的风险,了解该菌及相关疾病对于处理从地方性流行地区输入宠物的兽医人员至关重要。B pseudomallei 也被认为是潜在的生物恐怖主义病原体,考虑到该菌对公共卫生构成的潜在严重风险,一篇已发表的报告描述了对一只从泰国输入纽约的感染犬的公共卫生应对措施。9
在地方性流行地区,B pseudomallei 可从潮湿土壤和泥水中分离,这些是其主要的储存宿主。1–5 该菌在较深层土壤中数量较多,降雨期导致该菌渗滤至表层,增加接触风险。2–4,8 暴发与土壤扰动有关,如再开发工程、洪水过后或地貌退化及地质事件。3,8 传播通常通过直接接触受污染的土壤或水,经吸入、摄入或经皮接种及开放伤口暴露。1–5 临床表现因物种、感染部位、疾病阶段甚至不同地理区域而异。2,3,5 在新加坡,人类最常见的表现为菌血症(60.3%)、深部器官脓肿(40.7%)和肺炎(33.1%;1,2)。无症状感染也似乎相对常见,长期休眠后再激活也是人类类鼻疽的特征。2 犬中可能存在类似情况,因为唯一现有且最近发表的血清学研究纳入了泰国156只收容犬,发现9/156(6%)对 B pseudomallei 血清学阳性。10
类鼻疽影响多种物种,包括猫、犬、绵羊、山羊、马、灵长类、鹿、大象、牛、骆驼、鳄鱼、斑马、鬣蜥和禽类。1,3,5 描述犬和猫类鼻疽的有限已发表数据主要为病例报告。目前,仅发表了1篇澳大利亚犬的报告、11 1篇泰国犬的报告、12 以及1个病例系列,仅描述了1970年在美国驻越南武装部队服役期间诊断的7只犬的组织病理学变化。13 关于猫,已描述了1篇马来西亚猫的报告、14 1篇新喀里多尼亚猫的报告、15 以及澳大利亚各2只猫的2篇报告。16,17 犬和猫中报告的体征多样,包括发热、体重减轻、嗜睡、皮肤脓肿、内脏器官脓肿、肺炎和败血症。11–17
我们描述了新加坡一群犬和猫中类鼻疽的临床方面,旨在提高对该病的认识,以促进疑似病例的早期诊断和适当治疗的实施。
材料与方法
伦理批准由 Mars Veterinary Health 兽医临床研究委员会授予。检索了新加坡一家急诊和专科转诊医院的电子医疗数据库,以识别2020年5月至2025年7月期间诊断为类鼻疽的客户拥有犬和猫。使用的检索词为“Burkholderia”、“pseudomallei”和“melioidosis”。如果可获得经细菌鉴定阳性的培养或 B pseudomallei 阳性PCR,犬和猫符合纳入条件。如果诊断为疑似但未经培养或PCR确认,则排除病例。所有符合纳入标准的病例均被纳入。
从医疗记录中收集的数据包括物种、品种、性别、绝育状态、就诊时年龄、并发或既往疾病、临床症状、症状持续时间、诊断检测结果、就诊前治疗、培养或PCR结果、治疗和病例结局。当可获得时,记录其他诊断检测的结果,包括血液学、生化、尿液分析和诊断影像学。所有病例数据由委员会认证的内科专科医师审查,所有胸部X线片由委员会认证的诊断影像学专科医师审查。
对于犬,若满足以下标准中的≥2项,则诊断为全身炎症反应综合征(SIRS):体温≥39.7°C或≤37.8°C、心率≥160次/分、呼吸频率≥40次/分、白细胞计数≥12×10⁹/L或≤4×10⁹/L或杆状中性粒细胞≥10%。脓毒症定义为存在感染且满足上述SIRS标准(也称为"Sepsis-2"标准),并存在器官功能障碍,定义为序贯器官衰竭评估评分≥2。18,19 脓毒性休克定义为在充分补液后收缩压仍≤90 mmHg(或平均血压<65 mmHg)且需要血管升压药支持,同时血乳酸浓度>2 mmol/L。19
结果
15只犬和3只猫符合纳入标准。在所有病例中,诊断均基于类鼻疽伯克霍尔德菌的阳性细菌培养及基质辅助激光解吸/电离-飞行时间质谱(Antech Veterinary Diagnostics,新加坡)鉴定。任何病例的诊断均未基于血清学或PCR。
信号特征
在纳入的15只犬中,7/15(47%)为未去势雄性,4/15(27%)为去势雄性,3/15(20%)为去势雌性,1/15(7%)为未去势雌性。在纳入的3只猫中,2只为去势雄性,1只为去势雌性。就诊时中位年龄为7.4岁(范围2.3-12岁)。在15只犬中,4只为杂交品种,2只为罗威纳犬,以下品种各1只:拳师犬、荷兰牧羊犬、松狮犬、喜乐蒂牧羊犬、拉布拉多寻回犬、英国史宾格犬、迷你雪纳瑞、西施犬和柴犬。在3只猫中,2只为家养短毛猫,1只为波斯猫杂交。
就诊前抗菌药物使用情况
在纳入的犬中,6/15在就诊时正在接受抗菌药物治疗。其中4只单用阿莫西林-克拉维酸,1只使用阿莫西林-克拉维酸联合甲硝唑,1只使用未指明的抗菌药物。所有3只患猫在就诊时均正在接受抗菌药物治疗,分别为阿莫西林-克拉维酸、多西环素和克林霉素各1只。
临床症状与诊断(犬)
诊断前症状的中位持续时间为13天(范围1-60天)。14/15(93%)的犬至少有一次记录到发热(犬直肠温度>39.3°C)。就诊时,13/15(87%)的犬符合SIRS标准,10/15(67%)符合脓毒症标准。在纳入的犬中,3/15(20%)就诊时即处于脓毒性休克状态或在住院期间发展为脓毒性休克。
在纳入的犬中,8/15(53%)就诊时存在一个或多个皮肤脓肿或开放性伤口(图1)。其中,1只同时被诊断为前列腺炎,1只同时被诊断为脓胸、多发性肺脓肿以及肾上腺、肠系膜淋巴结脓肿,并可能累及肝脏。在纳入的犬中,6/15(40%)被诊断为前列腺炎或前列腺脓肿。其中,5/6根据超声检查结果同时存在与脓毒性腹膜炎一致的改变,包括腹腔积液呈回声增强及肠系膜回声增强,其中3只经积液分析显示中性粒细胞性炎症伴细胞内细菌而确诊,其余2只未进行积液分析。在纳入的未去势雄性犬中,6/7被诊断为前列腺炎或前列腺脓肿,其余1只缺乏诊断性检查结果以确定是否存在前列腺疾病。在其余纳入的犬中,1只被诊断为产后乳腺炎,1只(去势雄性)被诊断为细菌性尿路感染,腹部超声检查无前列腺炎证据。
[图:2只犬(A和B来自一只犬,C和D来自另一只犬)的多发性皮肤脓肿和开放性伤口的照片。M]

临床症状与诊断(猫)
3/3的猫至少有一次记录到发热(猫直肠温度>39.5°C)。这些猫的年龄分别为11、60和77月龄。在3只猫中,1只根据超声检查结果与严重双侧肾盂肾炎一致及尿培养阳性,被诊断为由类鼻疽伯克霍尔德菌引起的肾盂肾炎。1只根据从患骨骨髓腔拭子培养,被诊断为右肱骨骨髓炎。该猫的计算机断层扫描(CT)结果与右肱骨骨髓炎一致(图2),组织病理学与化脓性骨髓炎一致。1只根据关节液样本培养,被诊断为左跗骨骨髓炎及相关的跗关节脓毒性关节炎。该猫的CT结果与累及左跗骨多块骨骼的骨髓炎一致。
[图:诊断为该部位骨髓炎的猫右肱骨原生CT重排矢状面重建图像]

血液学与生物化学
在纳入的犬中,11/15 只出现中性粒细胞增多,3/15 只出现中性粒细胞减少,1/15 只中性粒细胞计数在参考范围内。6/15 只犬记录到轻度非再生性贫血,6/15 只记录到不同程度血小板减少。纳入的 3 只猫中有 2 只出现轻度中性粒细胞增多,1 只出现轻度中性粒细胞减少。1 只猫有轻度非再生性贫血。10/15 只犬和 1/3 只猫记录到高球蛋白血症。6/15 只犬和 1/3 只猫记录到 1 种或多种肝胆酶活性轻度升高。2 只犬就诊时存在低血糖(均伴有感染性休克),2 只犬有轻度高胆红素血症(均伴有脓毒症)。
样本类型
在 8 只表现为皮肤脓肿或开放性伤口的犬中,有 7 只培养出类鼻疽伯克霍尔德菌阳性的样本类型为脓肿液体或开放性伤口拭子,1 只同时有皮肤脓肿和前列腺炎的犬,阳性培养来自尿液。在 6 只患有前列腺炎或前列腺脓肿的犬中,培养出类鼻疽伯克霍尔德菌阳性的样本类型为:2/6 为尿液,2/6 为前列腺脓肿液体,1/6 为前列腺冲洗液,1/6 为腹腔积液。其中 2 只犬的前列腺样本培养阳性,且提交了不止一种样本类型进行细菌培养,两只均从尿液和腹腔液中获得类鼻疽伯克霍尔德菌阳性培养。在患有感染性乳腺炎的犬中,阳性培养来自感染腺体脓性物质的拭子;在 1 只表现为嗜睡、厌食和发热,且体格检查及胸腹部影像学未发现感染灶的去势公犬中,获得阳性培养的样本类型为尿液。根据实验室方案,未对任何分离株进行抗菌药物敏感性试验,因为类鼻疽伯克霍尔德菌被视为生物安全三级病原体。
诊断影像学
8/15 只犬进行了胸部影像学检查,其中 8 只均进行了胸部X线摄影,2 只进行了胸部X线摄影和CT。在这 8 只犬中,3/8(38%)有与多发性肺脓肿相符的改变(图3),且每只犬均主要以多发性皮肤脓肿就诊。8/15 只犬进行了完整的腹部影像学检查,另有 2 只(均患有前列腺炎或前列腺脓肿)仅进行了泌尿系统重点超声检查。在 8 只进行完整腹部影像学检查的犬中,7 只进行了腹部超声检查,1 只进行了CT检查。在这 8 只犬中,4 只被诊断为前列腺炎或前列腺脓肿,1 只为多发性皮肤脓肿,1 只为脓胸和多发性肺脓肿,1 只为乳腺炎,1 只为尿路感染。在这 8 只犬中,仅 1 只犬发现与前列腺以外任何器官感染或脓肿相符的影像学改变,该犬患有脓胸和多发性肺脓肿,CT改变与双侧肾上腺脓肿、多发性肠系膜淋巴结脓肿以及可能早期多灶性肝脓肿相符。
[图:一只患有类鼻疽且推测有多发性肺脓肿的犬的胸部背腹位(A)和右侧位(B)X线片]

可能导致免疫受损的既往或并发疾病或用药
在 3 只猫中,2 只在就诊时进行了猫免疫缺陷病毒(FIV)和猫白血病病毒(FeLV;SNAP FIV/FeLV Combo Test,IDEXX)检测,两者均为阴性,第 3 只未检测。在任何猫中均未发现其他既往或当前免疫抑制状况。在纳入的犬中,5/15(33%)正在接受药物治疗或患有被认为可能造成免疫受损的疾病或生理状态,其中 2 只接受免疫抑制剂量的泼尼松龙(1 只用于慢性炎症性肠病,1 只用于无菌性脓肉芽肿性淋巴结炎),1 只因特应性皮炎接受奥拉替尼,1 只患有糖尿病,1 只近期分娩。
手术干预
2 只犬均患有单个大皮肤脓肿,进行了手术引流和脓肿冲洗。其他 6 只具有皮肤表现的犬有多发性脓肿或开放性伤口,未进行手术干预。在 4/6 只患有前列腺炎的犬中,进行了手术干预以进行脓肿引流、大网膜化和腹腔灌洗。2/6 只患有前列腺炎的犬未进行手术干预;1 只超声显示弥漫性前列腺改变并伴有腹腔积液,但无明显脓肿形成;1 只超声显示弥漫性前列腺改变并有多发性皮肤脓肿。患有乳腺炎的犬进行了乳房切除术。患有右肱骨骨髓炎的猫进行了手术清创和冲洗。
初始抗菌药物选择
在18只动物中,就诊时及鼻疽伯克霍尔德菌培养前最初开具的抗菌药物为:11只使用阿莫西林-克拉维酸联合氟喹诺酮类,3只单用阿莫西林-克拉维酸,2只使用克林霉素联合氟喹诺酮类,1只单用多西环素,1只使用甲氧苄啶-磺胺(TMPS)联合美罗培南。在18只动物中,4/18在培养结果可获得前死亡或被安乐死,其中1只接受阿莫西林-克拉维酸和马波沙星,1只接受克林霉素和马波沙星,1只单用阿莫西林-克拉维酸,1只接受美罗培南和TMPS。这4只犬均为脓毒症,其中2只就诊时处于脓毒性休克。
后续抗菌药物选择
在获得鼻疽伯克霍尔德菌培养阳性时仍存活的14只动物中,7/14(50%)更改了初始抗菌治疗,其中3只改为单用TMPS,1只改为头孢他啶联合TMPS,1只改为美罗培南联合TMPS,1只改为单用美罗培南,1只改为多西环素联合TMPS。在12/18出院的动物中,5/12单用TMPS出院,3/12使用阿莫西林-克拉维酸联合氟喹诺酮类出院,2/12单用阿莫西林-克拉维酸出院,1/12单用多西环素出院,1/12使用克林霉素联合恩诺沙星出院。在12只出院动物中,左肱骨骨髓炎的猫在接受阿莫西林-克拉维酸和恩诺沙星治疗期间于出院后22天死亡;1只存活但随访<3个月,计划完成20周TMPS疗程;1只在15天后失访,但出院时带4周阿莫西林-克拉维酸和恩诺沙星;9例可获得>6个月随访。在9例出院且有长期随访的病例中,抗菌治疗的中位持续时间为16周(范围4-24周)。所用抗菌药物的类型、持续时间和剂量见补充材料1。
基于犬就诊时生理状态的结果和存活
在18例中,3/18只犬就诊时处于脓毒性休克,这3只犬在医院内死亡或被安乐死。在18例中,8/18符合脓毒症标准但无脓毒性休克。其中,5/8存活至出院,1只在出院后<4周失访,1只在出院后<4周死亡,3/8在医院内被安乐死。因此,在11/18只就诊时伴有脓毒症(无论是否伴有脓毒性休克)的犬中,仅5/11存活至出院,且仅3/10(对失访病例进行删失)在出院后存活>4周。在18只动物中,5/18就诊时伴有SIRS但无脓毒症,2/18就诊时无SIRS。其中,7/18只就诊时无SIRS或伴有SIRS但无脓毒症的动物全部存活至出院及此后>4周。
总体结果和存活
在18只动物中,12/18(67%)出院,6/18(33%)在住院期间死亡或被安乐死。在12只出院动物中,1只存活但2周后失访,1只在出院后<4周因类鼻疽死亡,10只存活且可获得>4周随访。排除1例因随访<4周而无法纳入长期存活分析的病例后,归因于类鼻疽的死亡或安乐死发生于8/17(47%)例,其中6只未存活至出院,1只在出院后<4周死亡,1只因症状复发在诊断后515天被安乐死。其余9/17(53%)只动物中,6只在出院后1个月存活(范围1-43个月),3只因与类鼻疽无关的原因死亡或被安乐死。排除出院后4周内失访的病例后,9/17(53%)存活>4周且无症状复发,中位随访时间为724天(均值534天;范围36-1277)。病例结果见补充材料1。
空间和时间分布
图4显示了18例基于其主要居住地的空间分布。每只犬因归因于类鼻疽的临床症状首次就诊的月份见补充材料1。图5显示了新加坡的月平均降雨量和每月首次就诊的病例数。
[图:显示18例纳入病例分布的新加坡风格化地图。每个圆点表示该病例所在的位置]

[图:修改自新加坡气象局(https://www.weather.gov.sg/climate-climate-of-singapore/)的图表,详述]

讨论
尽管类鼻疽自1920年起已在人类中被认识,但在家养动物中报道不足。1–3 我们的研究结果表明,犬和猫的表现与人类的多系统表现相似,且皮肤脓肿形成(纳入犬的53%)和前列腺受累(纳入犬的40%,仅考虑纳入的未去势公犬时为85%)是该群体中的标志性特征。泌尿生殖系统和皮肤表现是人类的第二和第三常见表现,分别占病例的14%和13%。20 由于大雨会增加伯克霍尔德菌假鼻疽亚种的暴露,2–4,8 对感染的气象和空间模式进行了评估。未发现月度或季节性模式。这一发现可能是因为,尽管降雨量存在月度变化,但新加坡平均每年有171天下雨。或者,犬和猫可能像人类一样存在延长或可变的潜伏期。2 未观察到主观明显的病例空间聚集。基于该国的地理情况,未发现明显的疾病空间聚集并不令人意外,因为无论主要居住在岛上的何处,犬只散步和其他休闲活动都能轻松且近距离地进入乡村和绿地。
人类类鼻疽的危险因素包括男性、年龄较大、免疫抑制(例如给予皮质类固醇)以及合并症如糖尿病和慢性肉芽肿病。1,2,4,8,20 新加坡的人类病例年龄跨度为1个月至97岁,在≥45岁达到高峰,男女比例为4.5:1。1,4 类似地,犬显示出73%的雄性易感性。1,4,21 高达77%的受影响人类有合并症,主要是糖尿病(37%-60%;2,21,22)。尽管只有1只犬患有糖尿病,但33%的犬因药物或生理状态而存在潜在免疫抑制,其中2只接受了免疫抑制剂量的皮质类固醇(1只用于脓肉芽肿性淋巴结炎),1只接受了oclacitinib。因此,尽管健康动物易感,但免疫功能障碍可能使犬易患类鼻疽或影响其发病机制。
一个关键发现是前列腺感染的高患病率:85%的受影响未去势公犬患有前列腺炎或前列腺脓肿。这在兽医文献中未见报道,该发现与人类类鼻疽相似,其中前列腺脓肿影响18%-20%的男性患者。2,20,22–24 这一观察具有相关性,原因有二。首先,前列腺脓肿通常需要手术引流,因为单纯药物治疗可能失败并导致复发。2,22,23 其次,它强调对任何疑似公犬应进行尿液或前列腺采样。在人类中,前列腺类鼻疽与高菌血症和复发率相关。22,23 由于本研究中没有去势公犬患有前列腺炎,应考虑对感染犬进行去势,以防止前列腺成为复发的病灶,这与其他细菌性前列腺炎病例的标准方案一致。25
脓毒症休克组100%的死亡率与非脓毒症SIRS组100%的存活率相比,提供了预后基线。这一发现与某些地区人脓毒症性类鼻疽报告中高达90%的死亡率相似。26 脓毒症是人类不良结局的主要决定因素,尽管给予了适当的抗菌治疗,仍使死亡风险增加3.5倍。27 在最近一项人类类鼻疽研究中,脓毒症休克被发现在死亡预测中具有很强的预测价值,报告的院内死亡率调整比值比为29.14(95% CI,12.45-68.20;28),新加坡的一项大型病例系列也报告了类似发现,其中需要正性肌力支持的脓毒症休克在多变量分析中与住院死亡率显著相关。22 在我们的研究中,有脓毒症但无休克的犬死亡率为57%,与人类类鼻疽的结局相当。基于纳入的犬只,无脓毒症的犬无论是否伴有SIRS,预后似乎良好,此类犬100%长期存活。我们研究中的总死亡率为47%,高于人类类鼻疽最大前瞻性病例系列的报告,但在该病例系列中,总死亡率从最初5年的30%降至最后5年的9%。20 第二个病例系列报告了类似的死亡率随时间下降的现象,1989年至1996年间报告的死亡率为40%,但1998年至2007年间降至16%。4 初期较高的总死亡率与我们的研究中观察到的高死亡率相当。人类病例存活率的改善归因于执业者认识提高带来的更早诊断、包括头孢他啶或美罗培南在内的治疗方案更早建立以及重症监护管理的改进。4,20 从SIRS向脓毒症的快速进展凸显了有效治疗的机会窗口。如前所述,某些地区人类死亡率从约40%降至<10%是通过早期目标导向治疗和立即使用美罗培南或头孢他啶实现的。我们脓毒症队列中的高死亡率至少部分可能与在培养结果出来前的初始48-72小时内初始使用阿莫西林-克拉维酸或氟喹诺酮类药物有关。我们的发现支持在流行地区的脓毒症犬中,在等待培养结果期间经验性使用头孢他啶或美罗培南,尤其是在发现前列腺或皮肤感染灶时。
由于B pseudomallei是生物安全三级病原体,兽医实践中通常无法进行常规抗菌药物敏感性试验。然而,2024年达尔文指南指出,分离株具有一致的敏感性特征,获得性耐药罕见,这意味着标准经验性推荐高度可靠。29 在人类中,抗菌药物敏感性试验仅用于疾病复发或再燃。在没有抗菌药物敏感性试验或疾病意识的情况下,初始怀疑度低常导致使用阿莫西林-克拉维酸联合或不联合氟喹诺酮类的次优经验性治疗。人类数据显示B pseudomallei对亚胺培南(100%)、头孢他啶(99%)、多西环素(94%-99%)、阿莫西林-克拉维酸(94%-98%)和氯霉素(94%-96%;1,4)高度敏感。人类指南推荐强化期(静脉注射美罗培南或头孢他啶10-14天,严重或深部感染延长至4-6周),随后口服TMPS 3-6个月。29 试验表明,与历史方案相比,初始使用头孢他啶可将死亡率降低多达50%。30,31 此外,尽管总死亡率相似,阿莫西林-克拉维酸的72小时治疗失败率显著高于头孢他啶(25% vs 5%;32)。头孢他啶是一线选择,29-32 氟喹诺酮类因固有耐药而不推荐。2 在我们的队列中,初始经验性选择为次优且先于培养结果,17/18例与人类指南不一致。最常见的初始选择是阿莫西林-克拉维酸(14/18)和氟喹诺酮类(13/18)。培养后,仅50%(7/14)存活犬调整了治疗:6/14改为TMPS,仅3/14接受了头孢他啶或美罗培南。没有犬完成推荐的14天静脉疗程,可能由于费用和住院限制。尽管缺乏兽医专用折点,分离出B pseudomallei应立即促使临床医生转向经验性有效的强化期和根除期治疗。
在初始强化阶段之后,需要坚持完成充分的根除阶段,以尽量减少治疗失败和复发的风险。29 在人类中,复发的最重要决定因素是抗菌治疗的类型和持续时间,坚持适当方案12-16周而非8周者复发风险降低90%,且复发通常与抗菌药物依从性差相关。33,34 人类根除阶段推荐口服TMPS单药治疗,其他选择如阿莫西林-克拉维酸和多西环素被认为效果较差。29 纳入的动物中,出院时仅有5/12被处方TMPS用于根除阶段,另有5/12出院时使用阿莫西林-克拉维酸,2/12出院时使用多西环素或克林霉素。在存活者中,中位治疗持续时间为16周。纳入的动物中,10/18出院且出院后存活>4周(其中9只有>6个月的随访资料),仅1/10因疾病复发而被安乐死。因复发而被安乐死的动物是一只患有骨髓炎的猫,最初用克林霉素治疗,随后用多西环素治疗。其余9/10只犬(90%)没有与类鼻疽相关的体征复发。值得注意的是,所有5只使用TMPS出院的犬在随访期间均无临床复发。尽管有人提出阿莫西林-克拉维酸可能是根除阶段替代TMPS的合适选择,但我们的发现与人类建议一致,即TMPS应被视为犬和猫根除阶段的一线抗菌药物。
尽管仅纳入了3只猫,但2/3(66%)表现为骨髓炎的发现值得注意。在人类中,肌肉骨骼类鼻疽相对少见,约占病例的10%。20 我们的系列中2/3的猫以及既往报告中1/6的猫出现该发现,提示B pseudomallei在猫中对骨和关节组织具有亲和力。兽医应将类鼻疽纳入猫骨髓炎或化脓性关节炎的鉴别诊断,尤其是流行地区的猫或对标准治疗无反应的猫。纳入的3只猫中有2只进行了FIV和FeLV检测,均为阴性;在人类中,既存的人类免疫缺陷病毒感染不被视为发生类鼻疽的危险因素。2
本研究的回顾性性质带来了固有局限性,包括缺乏标准化的诊断和治疗方案。急诊和转诊医院的环境可能引入了对更严重或更复杂病例的选择偏倚。此外,猫的样本量小,无法就物种特异性表现得出确定性结论,尽管骨髓炎和肾盂肾炎的存在提示其疾病播散模式与犬和人类相似。
从One Health的角度来看,宠物中B pseudomallei的出现可作为环境风险的哨兵。CDC最近宣布美国部分地区为流行区,强调类鼻疽不再局限于传统的热带热点地区。2,6,7 在流行地区工作的兽医应了解该细菌的人兽共患潜力及其可能对人类的陪伴者和临床工作人员构成的风险。早期识别可能相容的临床体征,应在处理疑似和确诊病例时立即使用适当的个人防护装备。在人类医学中,感染者传播给医护人员的风险被认为较低,尽管人际传播被认为非常罕见,但可通过直接接触感染的体液或病变发生。35 澳大利亚曾因反复使用受污染的生理盐水冲洗伤口而发生5例人类皮肤类鼻疽聚集性病例,证明该细菌能够在医疗液体瓶和小瓶中存活。36 根据人类医学的建议,37 处理疑似或确诊类鼻疽病例的兽医临床工作人员在接触犬、体液和样本时应戴手套、穿隔离衣并戴外科口罩,且必须遵循严格的手部卫生。必须采取标准预防措施以避免针刺伤,并且似乎审慎的做法是不重复使用治疗确诊或疑似病例时使用的任何药物瓶或小瓶。在全球范围内,兽医应对任何表现为皮肤脓肿或开放性伤口的犬、患有前列腺炎的犬、患有骨髓炎的猫,或任何患有不明原因脓毒症或内脏器官脓肿的犬考虑该病原体。早期识别、使用适当抗菌药物(如美罗培南或头孢他啶)进行初始治疗,以及使用TMPS进行延长根除阶段,可能对提高生存率很重要。
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Introduction
Melioidosis is caused by the aerobic, gram-negative, mobile bacillus, Burkholderia pseudomallei, an environmental saprophyte with most cases occurring in tropical and subtropical regions. Although most commonly reported in Southeast Asia and Northern Australia, 1–5 the bacterium is considered endemic in at least 45 countries, with the Gulf Coast region of the United States recently declared an endemic region by the Centers for Disease Control and Prevention (CDC; 6-8). There are concerns regarding the possibility of spread to regions currently not considered endemic, and sporadic reports in non-endemic regions suggest that unrecognized foci might already exist.2 With the increasing movement of humans and animals across the globe, there is a risk of infected pets being imported from endemic regions to non-endemic regions, and awareness and an understanding of the bacterium and associated disease are important for veterinary staff dealing with pets imported from endemic regions. B pseudomallei is also considered a potential bioterrorism agent and, considering the potentially serious risks the bacterium poses to public health, a published report described the public health response to an infected dog imported into New York from Thailand.9
In endemic regions, B pseudomallei can be isolated from moist soil and muddy water, its primary reservoirs.1–5 The bacterium is found in higher numbers in deeper soil layers, and periods of rainfall result in percolation of the bacterium to the surface, increasing contact risk.2–4,8 Outbreaks have been associated with soil disruption such as with redevelopment work, after flooding, or with landform degradation and geological events.3,8 Transmission is usually by direct contact with contaminated soil or water, either by inhalation, ingestion, or percutaneous inoculation and exposure of open wounds.1–5 Clinical presentation varies depending on species, site of infection, stage of disease, and even among different geographical regions.2,3,5 In Singapore, the most common presentations in humans are bacteremia (60.3%), deep organ abscesses (40.7%), and pneumonia (33.1%; 1,2). Asymptomatic infection also appears relatively common, and reactivation after long periods of dormancy is also a characteristic of melioidosis in humans.2 Similar situations also might be true in dogs because the only existing, recently published serological study, which included 156 shelter dogs in Thailand, found that 9/156 (6%) were seropositive for B pseudomallei.10
Melioidosis affects a wide range of species, including cats, dogs, sheep, goats, horses, primates, deer, elephants, cattle, camels, crocodiles, zebras, iguanas and avian species.1,3,5 The limited published data describing melioidosis in dogs and cats consists primarily of case reports. Currently, only 1 report of a dog in Australia,11 1 report of a dog in Thailand,12 and a case series describing only the histopathologic changes in 7 dogs diagnosed while serving with the United States Armed Forces in Vietnam in 197013 have been published. Regarding cats, 1 report of a cat in Malaysia,14 1 report of a cat in New Caledonia,15 and 2 reports each of 2 cats in Australia16,17 have been described. Reported signs in dogs and cats are variable and include fever, weight loss, lethargy, cutaneous abscesses, abscessation of internal organs, pneumonia, and septicemia.11–17
We describe the clinical aspects of melioidosis in a population of dogs and cats from Singapore, with the aim of increasing awareness of the disease to facilitate earlier diagnosis and institution of appropriate treatment in suspected cases.
Materials and methods
Ethical approval was granted by Mars Veterinary Health Veterinary Clinical Studies Committee. The electronic medical database of a single emergency and specialist referral hospital in Singapore was searched to identify client-owned dogs and cats diagnosed with melioidosis between May 2020 and July 2025. Search terms used were “Burkholderia”, “pseudomallei”, and “melioidosis”. Dogs and cats were eligible for inclusion if a positive culture with bacterial identification or positive PCR for B pseudomallei was available. Cases were excluded if the diagnosis was suspected but without confirmation by culture or PCR. All cases meeting the inclusion criteria were included.
Data collected from the medical records included species, breed, sex, neuter status, age at presentation, concurrent or pre-existing diseases, clinical signs, duration of signs, diagnostic test results, treatment before presentation, culture or PCR results, treatment, and case outcome. When available, results of other diagnostic tests were recorded, including hematology, biochemistry, urinalysis, and diagnostic imaging. All case data were reviewed by a board-certified diplomate in internal medicine, and all thoracic radiographs were reviewed by a board-certified diplomate in diagnostic imaging.
For dogs, a diagnosis of systemic inflammatory response syndrome (SIRS) was made if ≥2 of the following criteria were met; temperature ≥39.7 °C or ≤ 37.8 °C, heart rate ≥160/min, respiratory rate ≥40/min, and white blood cell count ≥12 × 109/L or ≤4 × 109/L or ≥10% bands. Sepsis was defined as the presence of infection and those meeting the aforementioned criteria for SIRS (also considered the “Sepsis-2” criteria), and the presence of organ dysfunction defined as a Sequential Organ Failure Assessment score ≥2.18,19 Septic shock was defined as systolic blood pressure ≤90 mm Hg (or mean blood pressure <65 mm Hg) despite adequate hydration and necessitating vasopressor support and a blood lactate concentration >2 mmol/.19
Results
Fifteen dogs and 3 cats met the inclusion criteria. In all cases, the diagnosis was based on positive bacterial culture of B pseudomallei and identification by means of matrix-assisted laser desorption/ionization—time-of-flight mass spectrometry (Antech Veterinary Diagnostics, Singapore). Diagnosis was not based on serology or PCR in any case.
Signalment
Of the 15 included dogs, 7/15 (47%) were intact males, 4/15 (27%) were neutered males, 3/15 (20%) were neutered females, and 1/15 (7%) were intact females. Of the 3 included cats, 2 were neutered males, and 1 was a neutered female. Median age at presentation was 7.4 years (range, 2.3-12 years). Of the 15 dogs, 4 were cross breeds, 2 were Rottweilers, and 1 each was of the following breeds: Boxer, Dutch Shepherd dog, Chow Chow, Shetland sheepdog, Labrador retriever, English Springer spaniel, Miniature schnauzer, Shih Tzu, and Shiba Inu. Of the 3 cats, 2 were domestic shorthair, and 1 was a Persian cross.
Antimicrobials before presentation
Of the included dogs, 6/15 were receiving antimicrobials at presentation. These included amoxicillin-clavulanate alone in 4, amoxicillin-clavulanate and metronidazole in 1, and an unspecified antimicrobial in 1. All 3 affected cats were receiving antimicrobials at presentation, with 1 each receiving amoxicillin-clavulanate, doxycycline, and clindamycin.
Clinical signs and diagnoses (dogs)
Median duration of signs before diagnosis was 13 days (range, 1-60 days). Pyrexia (rectal temperature >39.3 °C for dogs) was documented on at least 1 occasion in 14/15 (93%) dogs. At presentation, 13/15 (87%) dogs met the criteria for SIRS and 10/15 (67%) met the criteria for sepsis. Of the included dogs, 3/15 (20%) presented in septic shock or developed septic shock during hospitalization.
Of the included dogs, 8/15 (53%) presented with 1 or multiple cutaneous abscesses or open wounds (Figure 1). Of these, 1 was also diagnosed with prostatitis, and 1 was also diagnosed with pyothorax, multiple lung abscesses, and abscessation of the adrenal glands, mesenteric lymph nodes, and possibly liver. Of the included dogs, 6/15 (40%) were diagnosed with prostatitis or prostatic abscessation. Of these, 5/6 also had changes consistent with septic peritonitis based on ultrasonographic findings, including the presence of echogenic abdominal effusion and hyperechoic mesentery, with 3 being confirmed based on fluid analysis showing neutrophilic inflammation with intracellular bacteria, and no fluid analysis was performed in the other 2. Of the included intact male dogs, 6/7 were diagnosed with prostatitis or prostatic abscessation, and the remaining dog lacked diagnostic test results to determine if prostatic disease was present. Of the remaining included dogs, 1 was diagnosed with mastitis post-whelping, and 1 (a neutered male) was diagnosed with bacterial urinary tract infection with no evidence of prostatitis on abdominal ultrasonography.
[图:Photos of 2 dogs (A and B from 1 dog, and C and D from another dog) with multiple cutaneous abscesses and open wounds. M]

Clinical signs and diagnoses (cats)
Pyrexia (rectal temperature >39.5 °C for cats) was documented on at least 1 occasion in 3/3 cats. The ages of the cats were 11, 60, and 77 months. Of the 3 cats, 1 was diagnosed with pyelonephritis caused by B pseudomallei based on ultrasonographic findings consistent with severe bilateral pyelonephritis and positive urine culture. One cat was diagnosed with osteomyelitis of the right humerus based on culture from a swab taken from the medullary cavity of the affected bone. This cat had computed tomography (CT) findings consistent with osteomyelitis of the right humerus (Figure 2) and histopathology consistent with suppurative osteomyelitis. One was diagnosed with osteomyelitis of the bones of the left tarsus and associated septic arthritis of the tarsal joint based on culture from a sample of joint fluid. This cat had CT findings consistent with osteomyelitis affecting multiple bones of the left tarsus.
[图:Native CT reformatted sagittal reconstruction images of the right humerus of the cat diagnosed with osteomyelitis of thi]

Hematology and biochemistry
Of the included dogs, 11/15 had a neutrophilia, 3/15 had neutropenia, and 1/15 had a neutrophil count within reference range. Mild, non-regenerative anemia was documented in 6/15 dogs, and thrombocytopenia of variable severity was documented in 6/15. Two of the 3 included cats had mild neutrophilia, and 1 had mild neutropenia. One cat had mild, non-regenerative anemia. Hyperglobulinemia was documented in 10/15 dogs and in 1/3 cats. Mildly increased activity of 1 or more hepatobiliary enzymes was documented in 6/15 dogs and in 1/3 cats. Two dogs had hypoglycemia at presentation (both with septic shock), and 2 dogs had mild hyperbilirubinemia (both with sepsis).
Sample types
In 7/8 dogs presenting with cutaneous abscesses or open wounds, the sample type that returned a positive culture for B pseudomallei was fluid from an abscess or a swab from an open wound, and in 1 dog that had both cutaneous abscesses and prostatitis, the positive culture was from urine. Of the 6 dogs with prostatitis or prostatic abscessation, the sample type that returned a positive culture for B pseudomallei was urine in 2/6, prostatic abscess fluid in 2/6, prostatic wash fluid in 1/6, and abdominal effusion in 1/6. In 2 of these dogs that returned positive culture results on samples from the prostate, more than 1 sample type was submitted for bacterial culture, and in both, positive cultures for B pseudomallei were obtained from both urine and abdominal fluid. In the dog with septic mastitis, the positive culture was from a swab of purulent material from the infected gland, and in 1 neutered male dog presenting with lethargy, anorexia, and fever, and with no focus of infection identified on physical examination or thoracic and abdominal imaging, the sample type from which positive culture was obtained was urine. Antimicrobial susceptibility testing was not performed on any isolate in accordance with the laboratory’s protocols, because B pseudomallei is considered a Biosafety Level 3 pathogen.
Diagnostic imaging
Thoracic imaging was performed in 8/15 dogs, with all 8 having thoracic radiography and 2 having thoracic radiography and CT. Of these 8 dogs, 3/8 (38%) had changes consistent with multiple lung abscesses (Figure 3) and each of these dogs presented primarily with multiple cutaneous abscesses. Complete abdominal imaging was performed in 8/15 dogs, with an additional 2 (both with prostatitis or prostatic abscessation) having only focused ultrasonography of the urinary system performed. Of the 8 dogs that had complete abdominal imaging, 7 had abdominal ultrasonography, and 1 had CT performed. Of these 8 dogs, 4 were diagnosed with prostatitis or prostatic abscessation, 1 with multiple cutaneous abscesses, 1 with pyothorax and multiple lung abscesses, 1 with mastitis, and 1 with urinary tract infection. Of these 8 dogs, imaging changes consistent with infection or abscessation of any organ aside from the prostate was only identified in 1 dog, which had pyothorax and multiple lung abscesses and CT changes consistent with bilateral adrenal gland abscesses, abscessation of multiple mesenteric lymph nodes, and possible early multifocal hepatic abscessation.
[图:Dorsoventral (A) and right lateral (B) radiographs of the thorax of a dog with melioidosis and presumed multiple lung ab]

Pre-existing or concurrent diseases or medications that could result in immune compromise
Of the 3 cats, 2 were tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV; SNAP FIV/FeLV Combo Test, IDEXX) at presentation and were negative for both, and the third was not tested. No other pre-existing or current immunosuppressive condition was identified in any of the cats. Of the included dogs, 5/15 (33%) were receiving medications or had a disease or physiologic state considered potentially immune-compromising, with 2 receiving immunosuppressive doses of prednisolone (1 for chronic inflammatory enteropathy and 1 for sterile pyogranulomatous lymphadenitis), 1 receiving oclacitinib for atopy, 1 had diabetes mellitus, and 1 had recently whelped.
Surgical intervention
In 2 dogs, both with single large cutaneous abscesses, surgical drainage and irrigation of the abscess was performed. The other 6 dogs with cutaneous manifestations had either multiple abscesses or open wounds, and surgical intervention was not performed. In 4/6 dogs with prostatitis, surgical intervention was performed for abscess drainage, omentalization, and abdominal lavage. Surgical intervention was not performed in 2/6 dogs with prostatitis; 1 that had diffuse prostatic changes on ultrasonography with abdominal effusion but without overt abscess formation, and 1 that had diffuse prostatic changes on ultrasonography and multiple cutaneous abscesses. Mastectomy was performed in the dog with mastitis. Surgical debridement and irrigation were performed in the cat with osteomyelitis of the right humerus.
Initial antimicrobial choice
Of the 18 animals, the antimicrobials initially prescribed on presentation and before culture of B pseudomallei were amoxicillin-clavulanate and a fluoroquinolone in 11, amoxicillin-clavulanate alone in 3, clindamycin and a fluoroquinolone in 2, doxycycline alone in 1, and trimethoprim-sulfonamide (TMPS) and meropenem in 1. Of the 18 animals, 4/18 died or were euthanized before culture results were available and, of these, 1 was receiving amoxicillin-clavulanate and marbofloxacin, 1 was receiving clindamycin and marbofloxacin, 1 was receiving amoxicillin-clavulanate alone, and 1 was receiving meropenem and TMPS. All 4 of these dogs were septic, with 2 presenting in septic shock.
Subsequent antimicrobial choice
Of the 14 animals alive at the time positive culture for B pseudomallei was received, the initial antimicrobial treatment was changed in 7/14 (50%), with 3 changed to TMPS alone, 1 changed to ceftazidime and TMPS, 1 changed to meropenem and TMPS, 1 changed to meropenem alone, and 1 changed to doxycycline and TMPS. Of the 12/18 animals discharged from the hospital, 5/12 were discharged with TMPS alone, 3/12 with amoxicillin-clavulanate and a fluoroquinolone, 2/12 with amoxicillin-clavulanate alone, 1/12 with doxycycline alone, and 1/12 with clindamycin and enrofloxacin. Of the 12 animals discharged from the hospital, the cat with osteomyelitis of the left humerus died 22 days after discharge while on treatment with amoxicillin-clavulanate and enrofloxacin; 1 was alive with <3 months of follow-up and with a plan to complete a 20-week course of TMPS, 1 was lost to follow-up after 15 days but had been discharged with 4 weeks of amoxicillin-clavulanate and enrofloxacin, and >6 months follow-up was available for 9 cases. Of the 9 cases discharged from the hospital and with long-term follow-up, the median duration of antimicrobial treatment was 16 weeks (range, 4-24 weeks). The type, duration, and dose of the antimicrobials used are presented in Supplementary Item 1.
Outcomes and survival based on dog physiologic status at presentation
Of the 18 cases, 3/18 dogs presented in septic shock and these 3 dogs died or were euthanized in the hospital. Of the 18 cases, 8/18 met the criteria for sepsis without septic shock. Of these, 5/8 survived to discharge, with 1 lost to follow-up <4 weeks after discharge and 1 died <4 weeks after discharge, and 3/8 were euthanized in the hospital. Therefore, of the 11/18 dogs that presented with sepsis, with or without septic shock at presentation, only 5/11 survived to discharge, and only 3/10 (censoring for the case lost to follow-up) survived >4 weeks after discharge. Of the 18 animals, 5/18 presented with SIRS without sepsis and 2/18 presented without SIRS. Of these, 7/18 animals that presented without SIRS or with SIRS without sepsis all 7 survived to discharge and for >4 weeks afterward.
Overall outcomes and survival
Of the 18 animals, 12/18 (67%) were discharged and 6/18 (33%) died or were euthanized during hospitalization. Of the 12 animals discharged, 1 was alive but lost to follow-up after 2 weeks, 1 died <4 weeks after discharge because of melioidosis, and 10 were alive with >4 weeks of follow-up available. With the exclusion of 1 case from long-term survival analysis because of <4 weeks follow-up being available, death or euthanasia attributed to melioidosis occurred in 8/17 (47%) cases, with 6 animals not surviving hospitalization, 1 dying <4 weeks after discharge, and 1 euthanized 515 days after diagnosis because of recurrence of signs. Of the other 9/17 (53%) animals, 6 were alive 1 month after discharge (range, 1-43 months) and 3 died or were euthanized for reasons unrelated to melioidosis. Excluding the case discharged and then lost to follow-up within 4 weeks, 9/17 (53%) survived for >4 weeks with no recurrence of signs, with a median follow-up duration of 724 days (mean, 534 days; range, 36-1277). Case outcomes are described in Supplementary Item 1.
Spatial and temporal distributions
Figure 4 presents the spatial distribution of the 18 cases based on where they primarily resided. The month in which each dog was first presented for veterinary attention for clinical signs attributable to melioidosis is presented in Supplementary Item 1. Figure 5 presents the average monthly rainfall for Singapore and the number of cases initially presenting in each month.
[图:Stylized map of Singapore demonstrating the distribution of the 18 included cases. Each dot indicates the location in wh]

[图:Graph modified from Meteorological Service of Singapore ( https://www.weather.gov.sg/climate-climate-of-singapore/ ) det]

Discussion
Although melioidosis has been recognized in humans since 1920, it has been under-reported in domestic animals.1–3 Our findings suggest that the presentation in dogs and cats resembles the multisystemic presentation in humans, and that cutaneous abscessation (53% of included dogs) and prostatic involvement (40% of included dogs and 85% when considering only the included intact male dogs) are the hallmark features in this population. Genitourinary and cutaneous manifestations are the second and third most common presentations in humans, occurring in 14% and 13% of cases, respectively.20 Because heavy rain increases exposure to B pseudomallei,2–4,8 meteorological and spatial patterns of infection were evaluated. No monthly or seasonal patterns were identified. This finding might be because, although monthly variations in rainfall exist, it rains on average 171 days of the year in Singapore. Alternatively, a prolonged or variable incubation period might exist in dogs and cats as in humans.2 No subjectively obvious spatial clustering of cases was observed. Based on the geography of the country, it is not surprising that an obvious spatial cluster of disease was not identified because there is easy and close access to rural and green areas for dog walking and other recreational activities, regardless of where one might primarily reside on the island.
Melioidosis risk factors in humans include male sex, older age, immunosuppression (eg, corticosteroid administration), and comorbidities such as diabetes mellitus and chronic granulomatous disease.1,2,4,8,20 Human cases in Singapore spanned 1 month-97 years, peaking at ≥45 years of age with a 4.5:1 male-to-female ratio.1,4 Similarly, dogs showed a 73% male predisposition.1,4,21 Up to 77% of affected humans have comorbidities, primarily diabetes mellitus (37%-60%; 2,21,22). Although only 1 dog had diabetes, 33% were potentially immunocompromised because of medications or physiological state, with 2 receiving immunosuppressive dosages of corticosteroids (1 for pyogranulomatous lymphadenitis) and 1 received oclacitinib. Thus, although healthy animals are susceptible, immune dysfunction may predispose dogs to melioidosis or influence its pathogenesis.
A key finding is the high prevalence of prostatic infection: 85% of affected intact male dogs had prostatitis or prostatic abscessation. Unreported in veterinary literature, this finding mirrors melioidosis in humans, where prostatic abscesses affect 18%-20% of male patients.2,20,22–24 This observation is relevant for 2 reasons. First, prostatic abscesses often require surgical drainage, because medical treatment alone can fail and result in relapse.2,22,23 Second, it emphasizes that urine or prostatic sampling is indicated in any suspected male dog. In humans, prostatic melioidosis correlates with high bacteremia and relapse rates.22,23 Because no neutered males in our study had prostatitis, castration should be considered in infected dogs to prevent the prostate from becoming a nidus for relapse, aligning with standard protocols for other cases of bacterial prostatitis.25
The 100% mortality in the septic shock group, compared with the 100% survival in the non-septic SIRS group, provides a prognostic baseline. This finding is similar to the mortality rate of up to 90% reported in humans with septicemic melioidosis in certain regions.26 Sepsis is a major determinant of poor outcome in humans, conferring a 3.5-fold increased risk of mortality despite appropriate antimicrobial treatment.27 Septic shock was found to be a strong predictor of death in a recent study of melioidosis in humans, with a reported in-hospital mortality adjusted odds ratio of 29.14 (95% CI, 12.45-68.20; 28), with similar findings reported in a large case series from Singapore where septic shock requiring inotropic support was significantly associated with inpatient mortality on multivariate analysis.22 In our study, the mortality rate of 57% for dogs with sepsis but without shock is comparable to outcomes in humans with melioidosis. Based on the included dogs, the prognosis appears good for those without sepsis, with or without SIRS, with 100% of such dogs surviving long-term. The overall mortality rate of 47% in our study is higher than that reported in the largest prospective case series of melioidosis in humans but, in that case series, the overall mortality rate decreased from 30% in the first 5 years to 9% in the final 5 years.20 A similar phenomenon of decreased mortality over time was reported in a second case series, where reported mortality rate between 1989 and 1996 was 40%, but decreased to 16% between 1998 and 2007.4 The initial higher overall mortality rates are comparable to the high rate seen in our study. Improved survival in human cases was attributed to earlier diagnosis because of increased awareness among practitioners, earlier institution of treatment protocols including ceftazidime or meropenem, and improvements in intensive care management.4,20 The rapid progression from SIRS to sepsis highlights a window of opportunity for effective treatment. As mentioned, the decrease in mortality rates in humans from approximately 40% to <10% in some regions was achieved by early goal-directed treatment and immediate use of meropenem or ceftazidime. The high mortality in our septic cohort might be at least partially associated with initial use of amoxicillin-clavulanate or fluoroquinolones during the first 48-72 hours, before culture results became available. Our findings support empirical use of ceftazidime or meropenem in septic dogs in endemic areas while awaiting culture results, particularly if a prostatic or cutaneous focus of infection is identified.
Because B pseudomallei is a Biosafety Level 3 pathogen, routine antimicrobial susceptibility testing is often unavailable in veterinary practice. However, the 2024 Darwin guidelines note that isolates share a uniform susceptibility profile and acquired resistance is rare, meaning standard empirical recommendations are highly reliable.29 In humans, antimicrobial susceptibility testing is reserved for disease recrudescence or relapse. Without antimicrobial susceptibility testing or disease awareness, low initial suspicion frequently results in suboptimal empirical treatment using amoxicillin-clavulanate with or without fluoroquinolones. Data from humans show high B pseudomallei susceptibility to imipenem (100%), ceftazidime (99%), doxycycline (94%-99%), amoxicillin–clavulanate (94%-98%), and chloramphenicol (94%-96%; 1,4). Guidelines for humans recommend an intensive phase (IV meropenem or ceftazidime for 10-14 days, extended to 4-6 weeks for severe or deep-seated infections), followed by PO TMPS for 3-6 months.29 Trials indicate that initial use of ceftazidime decreases mortality by up to 50% compared with historical regimens.30,31 Furthermore, although overall mortality is similar, amoxicillin-clavulanate results in a significantly higher 72-hour therapeutic failure rate than observed with ceftazidime (25% vs 5%; 32). Ceftazidime is the firstline choice,29–32 and fluoroquinolones are not recommended because of intrinsic resistance.2 In our cohort, initial empirical choices were suboptimal and preceded culture results, with 17/18 cases diverging from guidelines used in humans. The most frequent initial choices were amoxicillin-clavulanate (14/18) and fluoroquinolones (13/18). After culture, treatment was modified in only 50% (7/14) of surviving dogs: 6/14 were changed to TMPS, and only 3/14 received ceftazidime or meropenem. No dog completed the recommended 14-day IV course, likely because of cost and hospitalization constraints. Despite the lack of veterinary-specific breakpoints, isolating B pseudomallei should immediately prompt clinicians to transition to empirically effective intensive and eradication phase treatments.
After the initial intensive phase, adherence to an adequate eradication phase is required to minimize the risks of treatment failure and recurrence.29 In humans, the most important determinants of relapse are type and duration of antimicrobial treatment, with relapse risk decreasing by 90% in those who adhere to an appropriate regimen for 12-16 weeks rather than 8 weeks, and relapses are commonly associated with poor antimicrobial compliance.33,34 Oral TMPS monotherapy is recommended for the eradication phase in humans, with other options such as amoxicillin-clavulanate and doxycycline considered less effective.29 Only 5/12 of the included animals that were discharged from the hospital were prescribed TMPS for the eradication phase, with an additional 5/12 discharged with amoxicillin-clavulanate, and 2/12 discharged with doxycycline or clindamycin. Of the survivors, median treatment duration was 16 weeks. Of the included animals, 10/18 were discharged and survived > 4 weeks after discharge (with >6 months follow-up available in 9 of these), with only 1/10 euthanized because of disease recurrence. The animal that was euthanized because of recurrence was a cat with osteomyelitis initially treated with clindamycin followed by doxycycline. The other 9/10 dogs (90%) had no recurrence of signs associated with melioidosis. Notably, all 5 dogs discharged on TMPS had no clinical recurrence during the follow-up period. Although it has been suggested that amoxicillin-clavulanate might be a suitable alternative to TMPS for the eradication phase, our findings are in agreement with recommendations in humans that TMPS be considered the first-line antimicrobial for the eradication phase in dogs and cats.
Although only 3 cats were included, the finding that 2/3 (66%) presented with osteomyelitis is notable. In humans, musculoskeletal melioidosis is relatively uncommon, occurring in approximately 10% of cases.20 The finding that 2/3 cats in our series and 1/6 in the previous reports suggests B pseudomallei has an affinity for bone and joint tissues in cats. Veterinarians should include melioidosis in the differential diagnosis for osteomyelitis or septic arthritis in cats, particularly those in endemic regions or those not responding to standard treatment. Of the 2/3 included cats tested for FIV and FeLV, both were negative and, in humans, pre-existing human immunodeficiency virus infection is not considered a risk factor for development of melioidosis.2
The retrospective nature of our study introduced inherent limitations, including lack of standardized diagnostic and treatment protocols. The emergency and referral hospital-based setting might have introduced selection bias toward more severe or complex cases. Additionally, the small sample size for cats precludes definitive conclusions regarding species-specific manifestations, although the presence of osteomyelitis and pyelonephritis suggests a similarly disseminated disease pattern to that seen in dogs and humans.
From a One Health perspective, the emergence of B pseudomallei in pets serves as a sentinel for environmental risk. The recent CDC declaration of parts of the United States as endemic regions emphasizes that melioidosis is no longer restricted to traditional tropical hotspots.2,6,7 Veterinarians working in endemic regions should be aware of the zoonotic potential of this bacterium and the risk it might pose to human companions and clinical staff. Early recognition of potentially compatible clinical signs should prompt the immediate use of appropriate personal protective equipment when dealing with suspected and confirmed cases. In human medicine, the risk of transmission from an infected human to healthcare workers is considered low and although person-to-person transmission is considered very rare, it can occur as a consequence of direct contact with infected bodily fluids or lesions.35 A cluster of 5 cases of cutaneous melioidosis in humans occurred in Australia because of the repeated use of contaminated saline used for wound irrigation, demonstrating the ability of the bacterium to survive in bottles and vials of medical fluids.36 In accordance with the recommendations in human medicine,37 veterinary clinical staff dealing with suspected or confirmed cases of melioidosis should wear gloves, gowns, and a surgical mask when in contact with dogs, fluids, and samples, and strict hand hygiene must be followed. Standard precautions must be taken to avoid needle stick injuries, and it would appear prudent not to reuse any bottles or vials of medication used when treating a confirmed or suspected case. Globally, veterinarians should consider this pathogen in any dog presenting with cutaneous abscessation or open wounds, dogs with prostatitis, cats with osteomyelitis, or any dog with unexplained sepsis or abscessation of internal organs. Early recognition, initial treatment with appropriate antimicrobials such as meropenem or ceftazidime, and a prolonged eradication phase with TMPS might be important to improve survival rates.
Supplementary Material
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