Sporotrichosis refractory to conventional treatment: therapeutic success with potassium iodide

Sporotrichosis is a subcutaneous mycosis caused by dimorphic fungi of the genus Sporothrix. The authors report a case of fixed cutaneous sporotrichosis with therapeutic failure after 18 months of itraconazole and terbinafine associated with cryosurgery. The patient was cured after the introduction of saturated potassium iodide solution. Sporothrix brasiliensis was the identified species, presenting a susceptibility profile to itraconazole and terbinafine. This fact suggests that therapeutic failure is probably related to the host-fungus interaction rather than drug resistance. It is possible that the immunomodulatory action of the saturated potassium iodide solution may have played an important role in curing this patient.     

Therapeutic failure with itraconazole in sporotrichosis due to bariatric surgery

Sporotrichosis is a deep mycosis of subacute or chronic evolution, caused by the dimorphic fungus of the genus Sporothrix. The treatment is carried out with antifungal orally or intravenously. Therapeutic success can be affected by several factors, such as altered gastrointestinal physiology by surgery. More and more patients are submitted to bariatric surgeries and the literature for the alterations of the absorption of medications in this context is very scarce. We intend to contribute to a better understanding with this case report of cutaneous-lymphatic sporotrichosis in a patient after bariatric surgery without response to itraconazole treatment, even at high doses.     

伊曲康唑对合用药物药代动力学影响的机制探讨

目的：观察伊曲康唑对健康成年人肝细胞微粒体细胞色素P450同功酶1A2、3A4活性的作用，探讨伊曲康唑对合用药物药代动力学影响的机制，为临床上安全有效的联合用药提供实验依据。方法：采用健康成人肝细胞微粒体，分为对照组和不同浓度的伊曲康唑组，共12组，每组10个样本，伊曲康唑组分别加入血药浓度范围内不同对应浓度的伊曲康唑，对照组仅加入培养液，孵育30min后，再加入CYP450同工酶1A2和3A4的相应底物（分别为非那西丁和睾酮）再孵育40min。反应终止后用高效液相色谱仪测量代谢产物（分别为对乙酰氨基酚与6β-羟基睾酮）的峰面积代表1A2和3A4的相对活性。结果：各处理组细胞色素P450同功酶1A2的相对活性百分比与对照组比较无显著差异（P〉0．05），而同功酶3A4的相对活性百分比随伊曲康唑浓度增加逐渐减小，各处理组与对照组比较均有显著差异（P〈20．05或P％0．01）。细胞色素P450同功酶3A4的相对活性百分比减小到对照组50％时（IC50）伊曲康唑的浓度为0．14μg／ml。结论：伊曲康唑在临床应用血药浓度范围内，对健康成年人肝细胞微粒体细胞色素P450酶同功酶1A2的活性无显著影响，然而对细胞色素P450同功酶3A4的活性有抑制作用，直接影响经3A4代谢的合用药物的血药浓度、半衰期等药代动力学参数。     

伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者侵袭性真菌感染

目的 观察伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者侵袭性真菌感染(IFI)的疗效及安全性.方法 所有血液系统疾病住院患者,符合IFI的诊断标准,后者类型包括确诊IFI、临床诊断IFI、拟诊IFI.本研究为开放研究,疗程为4～6周,分静脉给药阶段和口服给药阶段.静脉给药共14d,最初2d剂量为400mg/d,分两次给药,给药间隔12h;其后12d,剂量为200ms/d,1次/d.静脉用药结束后,继续给受试者序贯伊曲康唑口服液维持治疗,推荐剂量400mg/d,分两次给药(200 mg,2次/d),共用2～4周.根据受试者的病情决定每1～2周进行疗效与安伞性评价.结果 227例入组患者治疗结束后有效率为75.33%,其巾痊愈率达47.14%;227例患者治疗后205例退热(90.3%),中位退热时间5 d(2～20 d);可评价的186例患者,真菌学清除率为69.89%.发生与药物相关的不良事件11例,无与药物相关的严重不良事件发生.结论 伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者IFI的疗效可靠,应用安全.     

变应性支气管肺曲菌病1例并文献复习

目的:提高对变应性支气管肺曲菌病(ABPA)的认识并引起对该病的重视.方法:对1例ABPA患者临床资料进行分析,并结合文献进行复习.结果:ABPA是一种慢性、免疫介导的,对寄生繁殖的曲菌过敏导致的非感染性、炎症性肺部疾病,常发生在支气管哮喘的患者.结论:目前对该病的诊断应采取多种手段,包括纤支镜检查,痰培养及影像学、免疫学等;长期吸入糖皮质激素与口服伊曲康唑能达到较好治疗效果,且最大限度减少副作用.     

Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution

We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups (P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. (P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group (P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.     

国产伏立康唑对临床分离病原真菌体外抗菌活性研究

目的了解国产伏立康唑对北京和我国其他地区临床分离的常见病原真菌体外抗菌活性。方法分别参照CLSIM27-A2和M38-A方案测定伏立康唑对144株酵母和82株产孢丝状真菌的抗菌活性。受试菌株包括念珠菌114株（含氟康唑获得性耐药白念珠菌）、新型隐球菌20株、阿萨希毛孢子菌10株、曲霉62株（含伊曲康唑耐药曲霉及两性霉素B不敏感曲霉）、镰刀菌10株、尖端赛多孢菌10株。结果伏立康唑对念珠菌（不包括氟康唑耐药和剂量依赖敏感白念珠菌）、新型隐球菌、阿萨希毛孢子菌的MIC50≤0．5mg／L、MIC90≤1mg／L；而对氟康唑获得性耐药白念珠菌MIC50和MIC90均〉16mg／L。对曲霉、尖端赛多孢菌的MIC50≤1mg／L、MIC90≤2mg／L，对镰刀菌的MIC50和MIC90分别为4mg／L和〉16mg／L。结论伏立康唑对多数酵母有较强的体外抗菌活性，尤其是对克柔念珠菌和光滑念珠菌等氟康唑天然耐药菌株。该药对多数产孢丝状真菌也有较好的体外抗菌作用，包括伊曲康唑耐药及两性霉素B不敏感的曲霉以及对多种抗真菌药物耐药的尖端赛多孢菌；但其对氟康唑获得性耐药白念珠菌有一定交叉耐药。     

多种药物对体外培养泡球蚴作用的观察

目的观察6种药物单独或联合用药对体外培养泡球蚴的作用。方法泡球蚴体外培养5周后,收集囊泡,随机分为17组,每组约120~140个囊泡,分别加入不同药物进行培养,①单独用药组:阿苯达唑组(1μg/ml、10μg/ml)、伊曲康唑组(0.7 mg/ml)、伊维菌素组(1.75 mg/ml)、米替福新组(0.5μg/ml、2.5μg/ml和7.5μg/ml)、硝唑尼特组(0.1μg/ml、1μg/ml和10μg/ml)、利福平组(10μg/ml);②联合用药组:硝唑尼特联合阿苯达唑10μg/ml+10μg/ml组、10μg/ml+1μg/ml组、1μg/ml+10μg/ml组和1μg/ml+1μg/ml组;③对照组:二甲基亚砜组(2μl/ml)和空白对照组。培养6周,观察囊泡塌陷情况,对囊泡进行计数,并绘制囊泡曲线。6周后停药,联合用药组连续观察3周、3个月和6个月,观察泡球蚴囊泡生长情况。将各药物组体外培养的泡球蚴接种于雌性BALB/c小鼠,饲养8周后处死并剖检观察小鼠腹腔内有无泡球蚴生长并称重,测试泡球蚴活力。结果伊维菌素、米替福新和利福平对泡球蚴无抑制或杀灭作用。阿苯达唑、伊曲康唑、硝唑尼特,及硝唑尼特与阿苯...     

伊曲康唑预防血液肿瘤患者粒细胞减少期并发真菌感染的疗效观察

目的:探究应用伊曲康唑口服液预防血液肿瘤患者化疗后粒细胞减少期并发真菌感染的效果.方法:将62例化疗后中性粒细胞减少的血液肿瘤患者随机分为真菌感染预防用药组和对照组,其中预防用药组患者预防性地服用伊曲康唑口服液,而对照组患者未接受任何预防性抗真菌药物治疗.观察并比较2组患者真菌感染的发生率和严重程度.结果:31例服用伊曲康唑口服液患者中,仅2例发生真菌感染,真菌感染率仅为6.5%,而对照组31例中,8例并发真菌感染,包括3例深部真菌感染,真菌感染率为25.8%,明显高于预防用药组(P<0.01),而且2组患者并发真菌感染的病原菌存在明显差异.结论:预防性应用伊曲康唑口服液能有效降低血液肿瘤患者化疗后粒细胞减少期真菌感染的概率.     

伊曲康唑预防急性白血病患儿侵袭性真菌感染的临床研究

目的：评价伊曲康唑口服液在急性白血病（AL）患儿化疗后粒细胞缺乏伴感染时侵袭性真菌感染（IFI）预防性治疗的效果。方法回顾性分析2009年6月-2013年6月我院收集的AL化疗后伴粒细胞缺乏的213例患儿,将其分为伊曲康唑早期预防组和晚期预防组。伊曲康唑早期预防组（330例次）在粒细胞缺乏伴发热应用广谱抗生素同时服用伊曲康唑口服液;对照组（191例次）在粒细胞缺乏出现发热、经广谱抗生素应用72 h 后发热无改善者加用伊曲康唑口服液,比较两组患儿IFI发生率。结果伊曲康唑早期预防组和对照组各有7例和18例发生IFI,发生率分别为2.12％和9.42％,两组IFI发生率差异有显著性（P＜0．01）。结论 AL化疗后粒细胞缺乏患儿在发热早期进行预防性口服伊曲康唑可以有效降低IFI的发生率。