造血干细胞移植中氟康唑与伊曲康唑短疗程预防真菌感染的观察

目的比较异基因造血干细胞移植患者应用氟康唑和伊曲康唑预防侵袭性真菌感染的疗效及安全性。方法回顾分析192例异基因造血干细胞移植患者予短疗程（30d）氟康唑或伊曲康唑行真菌一级预防,其中应用氟康唑134例,伊曲康唑58例,比较两组患者侵袭性真菌感染的发生和转归情况。结果氟康唑组和伊曲康唑组移植30、60、90、180d侵袭性真菌感染的发生率分别为9.0%和5.2%、16.5%和6.9%、17.2%和8.7%、22.0%和16.4%,差异均无统计学意义（P值分别为0.370、0.081、0.128、0.309）,但移植后60d时P值明显较小。真菌感染发生部位均以肺部为主。患者均能很好耐受两药,但伊曲康唑副反应较大（19.0%vs2.2%,P=0.000）。结论短疗程伊曲康唑与氟康唑预防异基因造血干细胞移植后侵袭性真菌感染在移植60d时伊曲康唑较氟康唑显示了一定的优势。     

抗真菌药治疗念珠菌性阴道炎疗效对比

目的　比较伊曲康唑、特比萘芬、氟康唑 3种不同抗真菌药物对念珠菌性阴道炎的疗效 .方法　念珠菌性阴道炎 189例 ,分为 3组 ,分别给予伊曲康唑、特比萘芬、氟康唑进行治疗 .结果　伊曲康唑、特比萘芬、氟康唑治疗念珠菌性阴道炎的有效率分别是 93.7%、92 .1%和 90 .5 % (p >0 .0 5 ) ,不良反应发生率分别是 6 .3%、11.1%和 9.5 % .结论　 3种药物的疗效相似 ,不良反应发生率较低     

假丝酵母菌药敏实验及影响药物敏感性的因素分析

目的了解深圳地区育龄妇女外阴阴道假丝酵母菌的耐药情况及药物敏感性,探讨影响其药物敏感性的因素,为外阴阴道假丝酵母菌病（vulvovaginal candidiasis,VVC）的治疗提供参考依据。方法从体检妇女人群中阴道分泌物培养念珠菌感染阳性病例中选择103例为研究对象,对样本采用氟康唑、两性霉素B、伊曲康唑、酮康唑、益康唑进行药物敏感性实验;并回顾性调查检测对象病史、用药情况等。结果研究对象平均年龄（36.16±6.72）岁,文化程度以初中、高中和大专为主,分别占14.3%、29.7%和52.0%。对5种药物都敏感的样本有55例,占53.5%,对1种以上药物不敏感的样本有48例,占46.5%。药物敏感性依次是：两性霉素B（97.0%）、酮康唑（94.2%）、伊曲康唑（92.2%）、氟康唑（80.6%）、益康唑（72.8%）。近期使用抗生素更加容易使菌株对伊曲康唑和益康唑产生不敏感。使用抗生素的对象对两性霉素B、伊曲康唑、益康唑的耐药率分别为7.1%、14.3%和35.7%;而没有使用抗生素的对象对两性霉素B、伊曲康唑、益康唑的耐药率分别为2.3%、6.7%和25.8%。反复感染者的样本对两性霉素B（100.0%）和酮康唑（100.0%）非常敏感,但是会增加对伊曲康唑（8.7%）和益康唑（30.4%）的不敏感性。结论深圳地区外阴阴道假丝酵母菌整体耐药性较少,但近期使用抗生素和反复感染者对药物的敏感性有影响。临床治疗宜首选两性霉素B和酮康唑,反复感染者建议联合用药治疗。     

抗真菌药治疗念珠菌性阴道炎疗效对比

目的比较伊曲康唑、特比萘芬、氟康唑3种不同抗真菌药物对念珠菌性阴道炎的疗效.方法念珠菌性阴道炎189例,分为3组,分别给予伊曲康唑、特比萘芬、氟康唑进行治疗.结果伊曲康唑、特比萘芬、氟康唑治疗念珠菌性阴道炎的有效率分别是93.7%、92.1%和90.5%(p>0.05),不良反应发生率分别是6.3%、11.1%和9.5%.结论 3种药物的疗效相似,不良反应发生率较低.     

儿童真菌感染的病原学研究

目的探讨广州地区儿童真菌感染的病原分布特点及其耐药状况,为防治儿童真菌感染提供实验室依据。方法对患儿感染部位的真菌进行分离培养和鉴定：以ATB^TM FUNGUS3酵母样真菌药敏试验条进行常用抗真菌药物的敏感性分析。结果从患儿标本中分离出558株真菌,主要来自呼吸道有299株,占53．58％;其次是消化道、伤口（创口）、泌尿系统和血液等,分别占28．14％、6．27％、4．66％、3．76％。其中白色假丝酵母菌367株,占65．77％;其次为热带假丝酵母菌、光滑假丝酵母菌、近平滑假丝酵母菌、克柔假丝酵母菌、季也蒙假丝酵母菌等,分别占15．28％、5．02％、4．48％、3．41％、2．69％。从骨髓中检出5株马尔尼菲青霉,从脑脊液中检出3株新型隐球菌。真菌对两性霉素B、5-氟胞嘧啶、氟康唑、伊曲康唑、伏立康唑等总耐药率分别为8．78％、4．84％、10．54％、1．36％、0．85％。结论引起儿童真菌感染的主要病原菌是白色假丝酵母菌。对真菌感染应该有针对性地使用高效的抗真菌药物进行早期治疗。     

816株真菌感染分布及药敏分析

目的了解本院医院感染真菌分布的特点及对常用抗真菌药物的耐药情况。方法CHROMagar显色培养基及ATB真菌试剂盒进行鉴定;药敏试验采用纸片扩散K—B法。结果2008年1月至2009年6月我院临床共分离真菌816株,其中白色念珠菌（占53．2％）是引起真菌感染的最常见菌种,其次是热带念珠菌（21．6％）、光滑念珠菌（15．6％）、近平滑念珠菌（5．0％）和克柔念珠菌（2．3％）。药敏试验结果显示各种真菌对两性霉素B、制霉菌素的敏感性最高,分别达98％和99％,其次是氟康唑、伊曲康唑。结论真菌感染率呈逐年上升趋势,耐药率也逐渐增高。因此应及时对送检标本进行真菌培养和药敏试验,合理使用抗真菌药物,减少医院感染多重耐药和深部真菌感染的发生。     

伏立康唑与两性霉素B脂质体治疗艾滋病合并播散性马尔尼菲青霉菌病的对照研究

目的比较伏立康唑和两性霉素B脂质体治疗艾滋病（AIDS）合并播散性马尔尼菲青霉菌病（PSM）的疗效及安全性。方法对经血/骨髓培养确诊为AIDS合并PSM的患者,分别给予伏立康唑和两性霉素B脂质体治疗,疗程28d,比较两组的疗效和安全性。结果共52例患者纳入研究,其中伏立康唑治疗组20例,两性霉素B脂质体治疗组32例。治疗14d和28d时,伏立康唑组和两性霉素B脂质体组的治疗有效率分别为40.0%、65.0%和56.3%、71.9%,两组比较差异均无统计学意义（Z=1.300,P=0.254;Z=0.273,P=0.601）,但两组28d的治疗有效率均明显高于14d（Z=3.994,P=0.046）。治疗过程中,两组均未出现因毒副作用停药的现象,但两性霉素B脂质体组临床毒副反应较重且出现了血清肌酐的升高。结论伏立康唑与两性霉素B脂质体均为治疗AIDS合并PSM的有效方法,但伏立康唑安全性更好。     

氟康唑联合聚维酮碘溶液治疗生殖器念珠菌病疗效观察

目的 比较联合应用氟康唑和聚雏酮碘与单用氟康唑治疗生殖器念珠菌病的疗效。方法 选择142例门诊生殖器念珠菌病患者，随机分为两组，治疗组79例，对照组63例。治疗组口服氟康唑片，同时应用聚维酮碘涂抹患处，对照组单用氟康唑口服。疗程均为两周。结果 治疗结束时，治疗组有效率93.7％，对照组87．3％；疗程结束后两周复查，治疗组总有效率为97．5％。对照组为92．1％，治疗组与对照组相比，有显著性差异。结论 联合应用氟康唑和聚维酮碘治疗生殖器念珠菌病优于单用氟康唑。     

儿童马尔尼菲青霉菌感染的鉴定及该菌酵母相的体外药敏分析

目的确定患儿体内所感染的病原体为马尔尼菲青霉菌（PM），并用E—test法测定该菌酵母相的药物敏感性，指导临床合理用药。方法取患儿血液、骨髓涂片染色镜检和真菌双相培养，观察真菌生长情况及菌落形态，显微镜下观察菌体特征。并采用M27-P方案中的E—test法测定6株PM的酵母相（yeast）对伊曲康哇、酮康哇、5-氟胞嘧啶、氟康唑、两性霉素B的MIC值。结果PM为双相性真菌，于25℃为青霉相，于57℃为酵母相，并均有典型的菌落形态特征。瑞氏染色可见菌体呈圆形、椭圆型或腊肠样，大小不一，直径2～8pm，胞壁染紫色且清楚连续，在腊状的细胞内可见一明显的横隔。该菌37℃酵母相时伊曲康哇、酮康哇、5-氟胞嘧啶、氟康唑、两性霉素B的MIC范围分别为0．002—0．016μg／mL、0．012～0．125μg／mL、0．032～0．380μg／mL、1．500-6．000μg／mL、0．047～2．000μg／mL，对酮康唑、5-氟胞嘧啶出现耐药株各1株，对两性霉素B耐药株2株。结论马尔尼菲青霉菌的特征性菌落形态和骨髓及外周血发现的真菌孢子对该菌有诊断价值，而药敏结果显示该菌对伊曲康唑敏感性最强,其次为5-氟胞嘧啶、氟康唑、酮康唑 ,两性霉素B敏感性最弱。     

伊曲康唑联合阿莫罗芬乳膏治疗马拉色菌相关性皮肤病的疗效观察

目的 观察口服伊曲康唑胶囊联合外用阿莫罗芬乳膏治疗几种常见马拉色菌相关性皮肤病的临床疗效。方法 选择2017年2月~9月我科门诊收治的经临床确诊的花斑糠疹、马拉色菌毛囊炎、脂溢性皮炎患者270例,随机分为治疗组136例和对照组134例。对照组患者口服伊曲康唑胶囊治疗,治疗组在此基础上对患者皮损处外用阿莫罗芬乳膏,比较两组临床疗效及不良反应情况。结果 治疗组花斑糠疹、马拉色菌毛囊炎、脂溢性皮炎的治疗总有效率分别为92.86%、83.34%、83.34%,高于对照组的71.43%、52.94%、43.34%,差异有统计学意义（P＜0.05）;对照组5例患者口服伊曲康唑出现轻度胃肠道不适症状,治疗组2例患者皮疹部位轻度灼热,均不影响继续治疗,疗程结束停药后均消失。两组不良反应发生情况比较,差异无统计学意义（P＞0.05）。结论 口服伊曲康唑胶囊联合阿莫罗芬乳膏外用治疗马拉色菌相关性疾病疗效确切,安全性高。     

Multicenter, Randomized, Open-Label Study Comparing the Efficacy and Safety of Micafungin versus Itraconazole for Prophylaxis of Invasive Fungal Infections in Patients undergoing Hematopoietic Stem Cell Transplant

This multicenter, randomized, open-label phase III study compared the efficacy and safety of micafungin and itraconazole in prophylaxis of invasive fungal infections in neutropenic patients undergoing hematopoietic stem cell transplants in China. Micafungin (50 mg/day i.v.) or itraconazole (5 mg/kg/day p.o.) was administered for ≤42 days. The primary endpoint, treatment success, was defined as no proven, probable, or suspected invasive fungal infection through therapy and the absence of proven or probable invasive fungal infection through the end of 4 weeks after therapy. Noninferiority of micafungin against itraconazole was established if the lower boundary of the 95% confidence interval (CI) was >10%. Of 287 patients, 283 were evaluable for efficacy (136 for micafungin, 147 for itraconazole, intent-to-treat population). Treatment success was documented in 92.6% (126 of 136) of micafungin-treated patients and 94.6% (139 of 147) of itraconazole-treated patients (95% CI, -7.562% to 3.482%; P?=?.48), indicating noninferiority of micafungin against itraconazole. Results were similar for patients treated per protocol. Whereas the rates of proven or probable invasive fungal infection were numerically higher with micafungin than itraconazole at 4.4% (6 of 136) and 1.4% (2?of 147), rates of suspected invasive fungal infection were similar at 5.9% (8 of 136) and 7.5% (11 of 147), respectively. More patients treated with micafungin than itraconazole completed the study (82.9% versus 67.3%, respectively). Significant differences in incidence of withdrawal due to an adverse event (4.4% versus 21.1%) and drug-related adverse events (8% versus 26.5%) were shown between micafungin and itraconazole (P?=?.00, chi-square test). Micafungin was as effective as itraconazole in preventing invasive fungal infections in patients with neutropenia. In comparison to itraconazole, treatment tolerance was much better with micafungin.     

新生儿重症监护病房真菌血症病原学及临床分析

目的探讨自2004年1月至2008年12月我院新生儿重症监护病房获得性真菌血症病原学及临床特征,为真菌血症防治提供依据。方法回顾分析5年中新生儿重症监护室发生的33例真菌血症的病原学和临床资料。结果33例真菌血症均为医院获得感染的假丝酵母菌,其中白色假丝酵母菌17株、热带假丝酵母菌10株、近平滑假丝酵母菌5株、光滑假丝酵母菌1株。结论假丝酵母菌属是新生儿重症监护病房真菌血症的主要致病菌,以白色假丝酵母菌最常见,但非白色假丝酵母菌也占较大比例;真菌血症与早产、极低体重儿、机械通气、静脉导管、全胃肠外营养等因素有关。5-氟脲嘧啶、伊曲康唑、两性霉素B和氟康唑对假丝酵母菌耐药性较低,氟康唑是治疗假丝酵母菌属的有效药物。     

Mycoses in Thailand: current concerns.

Scytalidium dimidiatum is the leading cause of fungal foot diseases in Thailand, in contrast to similar studies in which dermatophytes have been identified as the predominant pathogens. By contrast, the prevalence of Candida albicans in our study was only 2.6 approximately 3.0%. Scytalidium fungal foot infection is clinically indistinguishable from that caused by dermatophytes and should be included as a possible cause of treatment failure in tinea pedis and onychomycosis. Without proper culture identification, clinically diagnosed patients would be treated with a standard antifungal regimen leading to minimal response and be interpreted as drug resistant cases resulting in switching of drugs and more aggressive management procedures. Tinea capitis is another health problem in young children. However, for Microsporum canis and some ectothrix organisms, the effectiveness of treatment may be less than endothrix infection. Griseofulvin is still the mainstay antifungal although itraconazole and terbinafine are as effective. Pulse regimen may be another option with advantages of increased compliance and convenience. Two pulses of terbinafine may be sufficient for treating most cases of Microsporum infection, although additional treatment may be needed if clinical improvement is not evident at week 8 after initiating therapy. Chromoblastomycosis is another subcutaneous infection that requires long treatment duration with costly antifungal drugs. The most common pathogen in Thailand is Fonsecaea pedrosoi. Preliminary study of pulse itraconazole 400 mg/d 1 week monthly for 9-12 consecutive months showed promising results. The prevalence of Penicillium marneffei infection is alarming in HIV infected patients living in endemic areas. Diagnosis relies on direct examination of the specimens and confirmation by culture. Treatment regimens include systemic amphotericin B or itraconazole followed by long-term prophylaxis. Treatment outcome depends on the immune status of the patient.     

Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology

AIMS: To compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies. PATIENTS: 213 consecutive, afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies. METHODS: A randomised, double blind, single centre study. Patients were randomly assigned to receive fluconazole 50 mg or itraconazole 100 mg, both twice daily in identical capsules. An intention to treat analysis was performed on 202 patients, 101 in each group. RESULTS: Microbiologically documented systemic fungal infections occurred in four patients in each group. Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole. In all 202 patients, 29 proceeded to intravenous amphotericin (amphotericin B), 16 in the fluconazole group and 13 in the itraconazole group. Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group. All these infections were oral. No major differences were noted in the isolates of fungi in mouth washes and fecal samples. Overall mortality was 8.9% (18 deaths; seven in the fluconazole group, 11 in the itraconazole group). Mortality from microbiologically and clinically documented fungal infection was 4.5% (nine deaths; three in the fluconazole group, six in the itraconazole group). Median time to suspected or proven fungal infection was 16 days in both groups. None of these comparisons reached statistical significance (p < 0.05). No major clinical toxicity was noted and compliance was excellent. CONCLUSIONS: In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation, fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease. Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals.     

Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era

Antifungal prophylaxis regimens vary between centres, informed by local epidemiology and antifungal stewardship practices. The advantages of itraconazole over posaconazole prophylaxis include maintaining the utility of azole therapy for suspected breakthrough invasive fungal infection (bIFI). We examined the effectiveness and tolerability of itraconazole as prophylaxis in acute myeloid leukaemia (AML) patients. We sought to determine the rate of probable and proven bIFI in the context of itraconazole prophylaxis in a real-life setting. Eighty-four patients corresponded to 175 episodes of primary antifungal prophylaxis with itraconazole solution (200 mg twice daily) as prophylaxis supported by a dedicated clinical pharmacist during induction, re-induction and consolidation chemotherapy for AML between January 2010 and January 2014. Assessment of clinical course included blinded review of all radiology scans. Episodes of bIFI were categorised according to consensus criteria. A low rate of bIFI (6/175, 3.4 %) occurred with the use of itraconazole. Tolerance was excellent with adverse events consisting predominantly of deranged liver function tests reported in 7/175 (4 %). Therapeutic drug monitoring performed at clinicians’ discretion demonstrated appropriate levels in 12/14 (86 %). Persisting fever and suspicion of invasive fungal infection (IFI) led to empiric antifungal therapy with voriconazole or caspofungin in 33/175 episodes (19 %), ceased after a median of 5 days following investigation in 16/175 (9 %). In this setting, itraconazole is effective and well-tolerated as prophylaxis. An additional benefit was seen in empiric therapy of suspected bIFI with amphotericin formulations kept in reserve. Local epidemiology is vital in guiding prophylaxis strategy.     

Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.