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。     

甲磺酸左氧氟沙星联合治疗复治菌阳肺结核

目的：探讨甲磺酸左氧氟沙星联合治疗复治菌阳肺结核及耐多药结核病（M D r-TB）的预防和控制。方法：选择2006年10月—2010年10月连续收治且获得随访的188例甲磺酸左氧氟沙星联合治疗复治菌阳肺结核患者,将其分为治疗组和对照组。两组均采用2HZEA k/7HE方案,治疗组在HA kZE抗结核治疗的基础上加用甲磺酸左氧氟沙星,观察两组疗效。结果：治疗组加用甲磺酸左氧氟沙星,明显提高了痰涂片抗酸染色阴转率（78/95,达82.1%以上）,且明显优于对照组（48/86,55.8%）（P〈0.01）,治疗组患者肺部病灶吸收程度和空洞缩小范围均优于对照组患者（P〈0.01）。结论：甲磺酸左氧氟沙星联合治疗复治菌阳肺结核效果显著。     

快生长分枝杆菌软组织感染的鉴定及耐药性分析

目的分析快生长分枝杆菌(RGM)的耐药性及RGM感染患者的临床特征,为临床进一步认识RGM提供参考。方法选取北京大学第一医院10年间分离到的3株RGM,分别采用电离解析飞行时间质谱(MALDI-TOF MS)和基因测序法进行菌种鉴定,并进行药物敏感性试验。同时,分析RGM感染患者的临床特征。结果3株RGM均对阿米卡星、妥布霉素、亚胺培南和利奈唑胺敏感,对复方磺胺甲噁唑均耐药。临床分别使用左氧氟沙星、阿奇霉素和/或利福平进行经验治疗,感染鼻疽分枝杆菌和偶发分枝杆菌的患者痊愈出院,脓肿分枝杆菌感染患者病情稳定后带药出院。结论RGM对大环内酯类抗菌药物耐药性较强,临床经验用药应避免使用此类抗菌药物。     

关节腔积液中分离偶发分枝杆菌1例分析

包头医学院第三附属医院于2017年5月31日收治1例在关节腔积液中发现偶发分枝杆菌的患者,对其进行膝关节DR影像学诊断,采用美国BD公司普通血培养瓶对无菌体液进行增菌,延长培养时间4～7 d,并进行飞行时间质谱仪鉴定。确诊为偶发分枝杆菌感染后联合使用利奈唑胺和莫西沙星对患者进行治疗。结果显示,延长培养时间4～7 d可提高阳性率;感染偶发分枝杆菌后膝关节的X线影像发生改变,DR片示左膝关节骨密度稍增高致密,关节面边缘见骨赘形成,左胫骨踝间隆起变尖,关节间隙清晰,周围软组织影肿胀;使用飞行时间质谱仪可准确快速鉴定非结核分枝杆菌(NTM),以质谱图为证。联合使用抗菌药物利奈唑胺和莫西沙星3个月后病情好转。     

赛多孢霉属侵袭感染的临床特征及实验室检查分析

目的探讨侵袭性赛多孢霉属感染的临床表现和实验室检查特点。方法收集2011年1月至2017年4月收治的8例赛多孢霉属患者的临床资料,对赛多孢霉属感染相关病例的临床表现、诱发因素和实验室检查的特点进行回顾性分析。结果8例患者中检出尖端赛多孢霉6株,波氏赛多孢霉1株,多育赛多孢霉1株。外伤、环境暴露和免疫力降低是赛多孢霉属感染的常见诱发因素。标本直接镜检均查见有隔菌丝,阳性率100%。菌落生长速度相对较快,侵袭力强,菌落形态多样,呈白色羊绒状至黑酵母样,随着培养时间的延长,从菌落中心开始颜色逐渐变深,结合镜下形态可进行菌属的快速鉴别。结论侵袭性赛多孢霉属感染病程进展迅速,病情凶险,以尖端赛多孢霉感染最多见。应加强对赛多孢霉属感染疾病的认识,提高诊治水平。     

艾滋病合并肺结核患者的临床分析

将我院艾滋病合并肺结核患者60例随机分为给予左氧氟沙星联合化疗的观察组和仅给予常规化疗的对照组,观察化疗前后的抗酸杆菌涂片、结核杆菌培养情况以及呼吸功能。结果观察组患者的抗酸杆菌涂片、结核杆菌培养转阴例数多于对照组,一秒率FEV1/FCV、MMRC评分、6min步行距离均明显高于对照组。左氧氟沙星联合化疗有助于控制结核杆菌、改善呼吸功能,在艾滋病合并肺结核的治疗中具有积极价值。     

伏立康唑在不同人群个体化给药方案研究现状

正伏立康唑(voriconazole)属于第二代三唑类抗真菌药物,具有抗菌谱广、抗菌效力强的特点,尤其对于侵袭性曲霉、氟康唑耐药的念珠菌[1](如克柔念珠菌等)所致感染疗效好。加之良好的经济学特点[2],目前伏立康唑已经成为血液系统疾病[3]、免疫功能低下[4]、器官移植[5]患者治疗或预防用药的首选。一项多中心的观察性研究[6]发现,在多种抗真菌治疗方案中,单用伏立康唑组     

膝关节滑膜软骨瘤病1例

患者女性，52岁。4年前无明显诱因出现左膝关节疼痛，行走时加重，偶有行走时左膝关节突然“卡住”不能活动，稍作休息后，能自行缓解。无症状时左膝关节活动自如，未行任何治疗。近1年来左膝关节疼痛加重，严重时出现左膝关节肿胀。特别是近2个月来，左膝关节疼痛及交锁现象频繁发作，以“左膝关节紊乱综合征”人院。骨科检查：右膝关节活动正常，左膝外侧肿胀，无明显畸形，交锁征（＋），左膝关节间隙髌韧带内侧有压痛，关节间隙水平髌骨外缘近股骨下端触及一直径约3cm的包块，质中，边界清楚，能活动。按之酸痛，有摩擦感。髌骨活动度尚可，研磨试验（＋）。左膝不能完全伸直，回旋挤压试验（＋）。行左膝关节腔关节镜下滑膜软骨游离体摘除术，术中见关节腔内有较多的游离体形成，游离体呈白色胶冻状，大小不一，送病检。     

伏立康唑治疗血液病患者侵袭性真菌感染

目的分析伏立康唑治疗血液病患者侵袭性真菌感染（IFI）的疗效和安全性。方法69例血液病并发IFI患者，予以伏立康唑为主的抗真菌治疗，从临床表现、影像学和病原学3个方面评价疗效，同时观察药物的不良反应。结果伏立康唑治疗IFI总有效率67．3％。在病原菌明确的病例中，曲霉属和念珠菌属感染有效率均为70％，1例新型隐球菌感染为显效。单变量分析显示延长伏立康唑治疗疗程（P〈0．01）和患者基础病稳定（P=0．014）能显著提高疗效。多因素分析提示治疗疗程和基础病状况是影响伏立康唑疗效的主要因素。伏立康唑主要不良事件是神经精神症状、视觉异常和皮疹；56例可评价病例中8例（14．3％）因不能耐受药物相关不良事件而退出伏立康唑治疗。结论伏立康唑在治疗血液病患者IFI上具有广谱抗真菌功效，同时它所引发的不良事件较少且多能耐受。     

伏立康唑联合氯吡格雷和泮托拉唑致肝功能异常和心肌损伤加重临床报告

目的探讨伏立康唑联合氯吡格雷和泮托拉唑是否存在配伍禁忌,为临床安全用药提供参考。方法回顾性分析伏立康唑联合氯吡格雷和泮托拉唑致肝功能异常和心肌损伤加重1例的临床资料。结果患者因急性非ST段抬高型心肌梗死使用氯吡格雷(每日75 mg)和泮托拉唑(每日60 mg)等治疗,治疗第5天因肺部真菌感染加用伏立康唑(每日200 mg)治疗。治疗第9天(使用伏立康唑治疗第4天),患者感到极度乏力,查天冬氨酸转氨酶(AST)798 U/L,丙氨酸转氨酶(ALT)832 U/L,肌钙蛋白0.567μg/L,诊断不除外药物性肝损伤、心肌损伤加重。遂进行药物基因检测显示患者CYP2C19为~*1~*1野生型,停用伏立康唑,改为米卡芬净钠抗真菌治疗。治疗第14天(停用伏立康唑5 d后),复查AST 33 U/L,ALT 38 U/L,肌钙蛋白0.14μg/L,患者肝功能和心肌损伤指标基本恢复正常。治疗第35天,患者胸闷、胸痛症状基本缓解后出院。结论伏立康唑联合氯吡格雷和泮托拉唑可能存在潜在的配伍禁忌。     

Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum.

We report the in-vitro susceptibility of 27 clinical isolates of Scedosporium apiospermum and 43 of Scedosporium prolificans. S. apiospermum was resistant to fluconazole and flucytosine, with variable susceptibility to amphotericin B, itraconazole, ketoconazole and susceptible to miconazole. Voriconazole was much more active than fluconazole and flucytosine, more active than amphotericin B, itraconazole and ketoconazole and was as active as miconazole against S. apiospermum isolates. Voriconazole and the other six antifungal agents showed low activity against S. prolificans isolates.     

In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mold pathogens.

The in vitro activity of voriconazole was compared with that of itraconazole. Eighty-six isolates of pathogenic molds belonging to 23 species were tested by an agar dilution method in High Resolution medium. Voriconazole was more active than itraconazole against a number of hyaline molds, including several Fusarium spp. and Scedosporium prolificans. Voriconazole and itraconazole showed comparable good activity against several hyaline molds, including Penicillium marneffei and Scedosporium apiospermum, and a number of dematiaceous molds, including Bipolaris australiensis, Cladophialophora bantiana, several Exophiala spp., and several Fonsecaea spp. Our results suggest that voriconazole could be effective against a wide range of mold infections in humans.     

In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi

The in-vitro fungistatic and fungicidal activities of voriconazole were compared with those of itraconazole and amphotericin B. MICs for 110 isolates belonging to 11 species of filamentous fungi were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the three antifungal agents were also determined. The MIC ranges of the three compounds were comparable for Aspergillus flavus, Aspergillus fumigatus, Cladophialophora bantiana and Exophiala dermatitidis. Voriconazole and itraconazole were more active than amphotericin B against Fonsecaea pedrosoi, but the two azole agents were less active against Sporothrix schenckii. Voriconazole was more active than itraconazole or amphotericin B against Scedosporium apiospermum, but less active than the other two agents against two mucoraceous moulds, Absidia corymbifera and Rhizopus arrhizus. Voriconazole and amphotericin B were more active than itraconazole against Fusarium solani. With the exception of S. apiospermum, all the moulds tested had MLC50 values of < or =2 mg/L and MLC90 values of < or =4 mg/L against amphotericin B. Voriconazole and itraconazole showed fungicidal effects against five of the 1 1 moulds tested (A. flavus, A. fumigatus, C. bantiana, E. dermatitidis and F. pedrosoi) with MLC90 values of < or =2 mg/L. In addition, voriconazole was fungicidal for Phialophora parasitica. Our results suggest that voriconazole could be effective against a wide range of mould infections in humans.     

Prevalence and susceptibility testing of new species of pseudallescheria and scedosporium in a collection of clinical mold isolates

The prevalence of new species of Pseudallescheria and Scedosporium in a collection of 46 clinical isolates was analyzed. Strain identification was done by morphological and molecular methods. Four Scedosporium aurantiacum isolates were detected among the panel of clinical strains. The susceptibility profile of S. aurantiacum was similar to that of Scedosporium apiospermum.     

骨关节结核的影像诊断与误诊分析

目的 提高对骨关节结核影像学表现的认识，避免误诊。方法 回顾性分析38例术前诊断骨关节结核的手术病理资料及影像学资料。结果 本组术前影像学均诊断为骨关节结核，X线表现为骨质破坏、骨质疏松及相应部位软组织肿胀。CT表现为骨质破坏伴骨硬化缘环绕、死骨，冷脓肿形成及脓肿壁钙化。MRI表现为椎体骨炎、骨质破坏，或椎间盘破坏、椎间盘裂隙状强化及椎旁脓肿形成。手术病理证实33例为结核病变，诊断符合率86．8％，其中脊柱结核20例，髋关节结核5例，腕关节、膝关节、踝关节、骶髂关节结核各2例。结论 骨关节结核的影像学表现有相对的特征性，合理选择影像学检查方法对提高骨关节结核的正确诊断率大有帮助。     

In vitro synergistic interaction between amphotericin B and micafungin against Scedosporium spp

The in vitro interaction between amphotericin B and micafungin against 36 isolates of Scedosporium spp. has been evaluated using checkerboard assays and the minimal effective concentration endpoint. Synergy was found for 82.4% of Scedosporium prolificans isolates and for 31.6% of Scedosporium apiospermum isolates. Antagonism was not observed.     

Voriconazole in fungal keratitis caused by Scedosporium apiospermum

OBJECTIVE: To describe the first case, to the best of our knowledge, of posttraumatic Scedosporium apiospermum (ScA) keratitis successfully treated with systemic and topical voriconazole. CASE SUMMARY: A 19-year-old man was admitted to the hospital with an incisive wound of his left eye and the cornea totally sectioned after trauma with a cutter used in gardening. Initial empirical treatment was followed by systemic and topical voriconazole, and the eye did not have to be enucleated. Five months after the trauma, a penetrating keratoplasty and chamber intraocular lens implantation was performed with a favorable visual outcome. DISCUSSION: ScA keratitis is rare, but it must be suspected if a history of ocular injury with contaminated objects exists. Among the antifungals available to treat ScA keratitis, voriconazole has shown advantages such as the lowest minimum inhibitory concentration and the availability of an oral formulation. CONCLUSIONS: Voriconazole shows promise as an effective alternative to conventional antifungals in the treatment of ScA keratitis. It is available both as oral and intravenous preparations, which is a great advantage in these lengthy infections.     

Migrating Swollen Joint and Lyme Disease: A Case Report

This article discusses a case involving a pediatric patient who presented to a large urban children's hospital in the Northeastern United States with complaints of migratory monoarticular joint swelling. The patient had presented with a swollen and painful left knee but with no other associated symptoms. He was nontoxic appearing, afebrile, and had normal vital signs. On examination, he was noted to have a tender and swollen left knee that was not erythematous, bruised, or warm to the touch. There was a history of fevers over the summer after returning home from a camping trip in a park located in the northeastern United States. A plain film knee x-ray showed signs of joint effusion but no osseous abnormalities. A bedside ultrasonography of the knee showed a pocket of fluid in the joint space. With parental consent, the left knee joint was aspirated under direct ultrasound guidance, with collection of dark yellow synovial fluid. This was sent for analysis that included cultures, Gram stain, crystal analysis, and Lyme antigens. The patient was admitted, and his symptoms improved during his hospitalization. The results were positive for Lyme and he was discharged home on a 3-week course of Amoxicillin with complete resolution of his symptoms.     

In vitro activities of 35 double combinations of antifungal agents against Scedosporium apiospermum and Scedosporium prolificans

Activities of 35 combinations of antifungal agents against Scedosporium spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against Scedosporium apiospermum. Antagonism was absent for all antifungal combinations against both species.