伊曲康唑治疗复发性外阴阴道念珠菌病38例临床观察

目的了解国产伊曲康唑（商品名“美扶”）治疗复发性外阴阴道念珠菌病的疗效。方法收集38例复发性外阴阴道念珠菌病为治疗组,口服伊曲康唑200mg,1次／d,连续7d,以后每次月经第1天口服伊曲康唑200mg,1次／d,连续6个月经周期停药,而对照组20例则单子硝酸咪康唑栓200mg阴道外用,方法同前。两组完成冲击治疗后1周、3个月、6个月评价疗效。结果1周后治疗组总有效率为92．1％,对照组为90％,两组相比无统计学差异。3个月、6个月后治疗组的复发率分别为3．2％、6．7％,对照组为28．6％、38．5％,两组相比有统计学意义。结论伊曲康唑短程冲击治疗加长期间断给药对复发性外阴阴道念珠菌病的治疗和预防复发效果满意。     

Proteinase detection,DNA typing and antimycotic susceptibility of Candida isolates from Colombian women with vulvovaginal candidiasis

Forty non-pregnant Colombian women (ages 18-45) with vulvovaginal candidiasis diagnosis (VVC) were enrolled in a blinded study to compare the efficacy of Itraconazole (ITRA) 400 mg vs. Fluconazole (FLU) 150 mg. Sexual partners received similar therapy. Proteinase detection by the Staib method and minimal inhibitory concentration (MIC) for FLU and ITRA by Etest method were performed in all Candida isolates. Patients were followed one year to determine clinical evolution and recurrence of VVC (RVVC). The strain identity of the RVVC isolates was determined by contour-clamped homogeneous electric field (CHEF) gel electrophoresis karyotyping and restriction fragment length polymorphism (RFLP). Thirty patients (75%) had one or two episodes of VVC/year, 83% of these were due to Candida albicans, while ten patients (25%) developed RVVC (three or more episodes/year); seven of them were treated with FLU. Non-C. albicans Candida species were detected in five of 30 (17%) of the patients with VVC and in seven of ten (70%) patients with RVVC (p=0.003). Isolates from nineteen patients were proteinase positive. Proteinase production and type of treatment were not related to recurrence of VVC (p>0.05). DNA typing revealed that in this population RVVC might be due to the same strain, substrain shuffling or different strains and species.     

A Case of Relapsed Chromoblastomycosis Due to Fonsecaea monophora: Antifungal Susceptibility and Phylogenetic Analysis

Chromoblastomycosis is a chronic cutaneous and subcutaneous mycosis. The management of this infection continues to be challenging because there is no consensus on the therapeutic regimen. We report here a case of a 69-year-old male patient with cauliflower-like lesions on his left leg and foot. He had already been treated with itraconazole at a dose of 200 mg/day for 5 months, with mycological cure for all the affected areas. However, the lesions relapsed at both sites, and treatment with itraconazole was resumed at the dose previously used. Initially, direct mycological examination, cultural, and microculture slide observation were performed. Afterward, sequencing of the ITS1-5.8S rDNA-ITS2 region of the fungal DNA and evaluation of its susceptibility to antifungal agents alone and in combination were performed. In direct mycological examination, the presence of sclerotic cells was verified, and the fungus was identified as Fonsecaea based on cultural and microscopic examinations. Identification as Fonsecaea monophora was confirmed after sequencing of the ITS region and phylogenetic analysis. The isolate was susceptible to itraconazole and terbinafine. The combinations of amphotericin B and terbinafine and terbinafine and voriconazole were synergistic. The use of drugs for which the causative agent is susceptible to singly or in combination may be an alternative for the treatment of mycosis. Furthermore, the identification of the agent by molecular techniques is important for epidemiological purposes. To the best of our knowledge, this is the first case of relapsed chromoblastomycosis caused by F. monophora in Brazil.     

伊曲康唑序贯疗法治疗老年MODS患者侵袭性肺部真菌感染14例

目的 观察伊曲康唑序贯疗法治疗老年多脏器功能障碍综合征（MODS）患者侵袭性肺部真菌感染的疗效。方法 回顾分析重症监护病房（ICU）中,老年MODS患者侵袭性真菌感染14例,最初应用伊曲康唑注射液7～14d,第1～2d,200mg,1次／12h,第3～14d,200mg,1次／d;然后,采用伊曲康唑胶囊或口服液序贯治疗,400mg／d剂量水平,疗程2—4周。结果 临床有效率85．7％,真菌清除率为92．9％,真菌清除平均天数为6．1d;患者28d生存率85．7％,不良反应发生率为42．9％。结论 对老年MODS合并侵袭性真菌感染患者在综合治疗的基础上,应用广谱抗真菌药物——伊曲康唑序贯疗法,是巩固疗效,防止复发值得推广的给药方式。临床应用伊曲康唑时,应注意适应证、药物不良反应及药物的相互作用。     

伊曲康唑联合外用药物治疗花斑糠疹临床研究

目的探讨伊曲康唑胶囊联合1%盐酸布替萘芬乳膏和2%酮康唑洗剂治疗花斑糠疹的疗效及不良反应。方法入选患者按单双日分为两组,两组均口服伊曲康唑0.2g,1次/d,连续7d,同时外用1%盐酸布替萘芬乳膏,1次/d,连续14d,对照组停药观察,试验组同时使用2%酮康唑洗剂洗浴,每周2次,连用3个月。分别于治疗前、治疗后1、3、6、12个月评价疗效。结果试验组114例患者3个月时痊愈率78.1%,6个月时痊愈率90.4%,对照组125例患者3个月时痊愈率72.8%,6个月时痊愈率75.2%,12个月后试验组复发率1.8%,对照组为18.4%。结论伊曲康唑胶囊短时口服联合外用布替萘芬和酮康唑洗剂洗浴疗效较好,安全性高,使用方便,可大大降低花斑糠疹的复发率。     

乌鸡白凤丸巩固治疗复发性外阴阴道念珠菌病的临床研究

目的 应用乌鸡白凤丸巩固治疗复发性外阴阴道念珠菌病（Recurrent Vulvovaginal Candidiasis,RVVC）,通过观察其疗效及安全性,探讨其有无降低RVVC复发率的作用.方法 486名处于VVC急性发作且以往有RVVC史的非孕育龄妇女,急性期阴道给予克霉唑栓强化治疗.达到临床及真菌治愈标准后,随机分为3组采取不同方案进行巩固治疗或临床观察.A组：每月月经净后3～7 d,继续单次阴道给予克霉唑栓500 mg,为期3个月;B组：每月月经净后口服乌鸡白凤丸每次1丸,1次/d,3周为1个疗程,连用3个月.对照组：仅作随访观察.各组在巩固治疗期间及巩固治疗结束后6个月内进行随访,观察疗效及不良反应发生情况.结果 巩固治疗期间,A组和B组分别累计有17人（10.12％）和23人（13.61％）出现复发,显著低于对照组（P＜0.001）.巩固治疗结束后,随访第3个月A组和B组分别累计有31人（21.83％）和37人（26.62％）出现复发;随访第6个月A组和B组分别累计有73人（51.41％）和79人（56.83％）出现复发,均显著低于对照组（P ＜0.001）,A、B组间各阶段复发率无显著差异（P＞0.05）,不良反应轻微.结论 RVVC近期治愈后采用乌鸡白凤丸巩固治疗,能够抑制念珠菌生长,增强免疫功能,控制阴道局部炎症反应,有效预防复发,效果满意且相对安全,值得临床应用与推广.     

A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine-Resistant <Emphasis Type="Italic">Candida albicans</Emphasis>

Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence.     

伊曲康唑治疗严重烧伤患者真菌感染的疗效分析

目的 评价伊曲康唑治疗严重烧伤患者真菌感染的疗效及其安全性。方法 采用开放、随机研究单组评估设计,治疗前2d：伊曲康唑注射液2次／d,间隔12h,200mg／次。此后1次／d,剂量200mg,间隔24h,1疗程14d。试验结束后口服伊曲康唑口服液维持治疗至少4周,2次／d,200mg／次。结果 伊曲康唑治疗23例严重烧伤患者总有效率为60．87％;本组86．96％的患者临床疗效为改善;63．64％的患者真菌学疗效为真菌清除;8．70％和52．17％的患者综合疗效分别为痊愈和显效,未发生不良反应。结论 伊曲康唑治疗严重烧伤患者真菌感染有良好的疗效、不良反应少。     

In vitro susceptibility of fungal and yeast clinical isolates to itraconazole and voriconazole

The interest on the in vitro susceptibility to itraconazole has recently increased due the availability of the intravenous formulation. In this study, comparative MICs of this antifungal with voriconazole were carried out in 62 clinical isolates of filamentous fungi and 100 yeasts isolates using the NCCLS microbroth methods described in M38-A and M27-A2 documents. A MIC90 of 0.125 micrograms per ml was observed for itraconazole and voriconazole against Aspergillus fumigatus. Higher susceptibility to itraconazole was found for the filamentous form of Sporotrhix schenckii (p = 0.001). Voriconazole was more effective against Scedosporium apiospermium while Scedosporium prolificans isolates were resistant to both azoles. Some isolates of Rhizopus stolonifer were susceptible to itraconazole and resistant to voriconazole, but without statistical significance. Susceptibility of nine species of Candida was similar for both triazoles used in this study. However, Candida glabrata was more susceptible to voriconazole. Some fluconazole-resistant Candida albicans isolates were susceptible to itraconazole and / or voriconazole. Cryptococcus neoformans was more susceptible to itraconazole than to voriconazole. Itraconazole and voriconazole showed very close in vitro activity against the tested fungal isolated, except against S. schenckii. In spite of this, there were some differences in susceptibility among isolates within the same fungal species.     

Onychomycosis Due to Neoscytalidium Treated with Oral Terbinafine, Ciclopirox Nail Lacquer and Nail Abrasion: A Pilot Study of 25 Patients

Background

Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection.

Methods

Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation.

Results

Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84 %) entered the study with more than 50 % of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96 %, respectively, presented less than 25 % nail lesion. Negative microscopy was observed in 36 % of the patients at the end of treatment and in 24 % of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84 %) and in 18 (72 %) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4 %) presented complete cure, 8 (32 %) presented partial cure, 16 (64 %) presented therapeutic failure. At the end of follow-up period, 6 patients (24 %) were considered to have recurrence/reinfection.

Conclusions

The results obtained at the 6-month period of follow-up showed marked improvement (96 % of clinical improvement and 72 % of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.     

治疗复发性外阴阴道假丝酵母菌病的探导

目的探讨复发性外阴阴道假丝酵母菌病（RVVC）的治疗方法。方法确诊为RVVC的患者82例,用氟康唑加制霉菌素治疗至真菌学转阴后,随机分成2组：治疗组用上述抗真菌巩固后采用阴道乳酸杆菌活菌制剂治疗;对照组连续进行6个月的抗真菌巩固治疗。结果2组近期治愈率差异无显著性;而3个月复发率治疗组明显低于对照组,差异有显著性。结论乳酸杆菌活菌制剂（定君生）能够预防RVVC的复发。     

The Use of (1–3) β-Glucan Along with Itraconazole Against Canine Refractory Sporotrichosis

Sporotrichosis, caused by the Sporothrix schenckii fungal complex, is a zoonotic mycosis distributed worldwide. Itraconazole is the treatment of choice for domestic animals although some fungal isolates have shown resistance to this drug. The objective of this study was to report, for the first time, the use of (1–3) β-glucan along with itraconazole in the treatment of a canine with sporotrichosis caused by Sporothrix brasiliensis. The animal had ulcerated and crusted lesions, especially on the nasal planum. Clinical samples were collected for a complete blood count, cytological analysis of the lesion, and fungal culture. Based on the results of the laboratory examination, and after the fungal culture, antibiotic therapy and treatment with itraconazole were initiated. Two additional fungal cultures were performed, which were positive. After 7 months of the animal treatment with itraconazole, the S. brasiliensis culture was still positive, so that the itraconazole was associated with (1–3) β-glucan. After four weekly applications of glucan, the complete elimination of the fungus was observed based on the fungal culture negative results. The results show, therefore, that (1–3) β-glucan with itraconazole promoted the case resolution, and it may be considered a promising alternative for the treatment of sporotrichosis in cases of resistance to conventional therapy.     

Treatment of disseminated histoplasmosis in hamsters

A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out.Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g.All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups.In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.     

Interruption of antifungal secondary prophylaxis in AIDS-related histoplasmosis

The clinical data of 21 patients, suffering AIDS-related histoplasmosis, who were able to interrupt antifungal secondary prophylaxis, after achieving a partial restoration of the cell mediated immunity by HAART administration, are presented. They were 16 males and five females, whose ages varied between 32 and 54 years (mean = 38.5 years). All of them presented disseminated progressive forms of histoplasmosis, with multiple locations (skin, mucous membranes, liver, spleen, lymph nodes and lungs). The majority of the cases suffered other concomitant diseases (specially tuberculosis and Kaposi sarcoma), 66.6 % of the patients had less than 50 CD4+ cells/microl at the start of treatment and the average viral burden was 278,385 RNA copies/ml. The initial treatment consisted in 400 mg/day of itraconazole, by oral route, in 14 cases and the remaining seven patients were treated with amphotericin B, intravenously, at a daily dose of 0.7 mg/kg of body weight. One patient who did not tolerate amphotericin B and presented a partial response to itraconazole, was treated with posaconazole orally at a daily dose of 800 mg. Fourteen patients received oral itraconazole at a daily dose of 200 mg as a secondary prophylaxis, the remaining three patients were treated with intravenous amphotericin B, 50 mg twice a week. After HAART for an average lapse of 16.7 months (10 to 32 months), five cases showed CD4+ cells counts above 150 cells/microl and the remaining 16 presented more than 200 cells/microl; 18 of them had undetectable viral burden and all cases were asymptomatic. The follow up after secondary prophylaxis discontinuation varied between six months and six years (mean= 33.6 months). Twenty out of 21 patients (95 %) were clinically stable, without any manifestation of relapses, including two patients who abandoned HAART. One patient, who discontinued HAART, contracted a fatal bacterial pneumonia. Even though the limited number of cases, the data presented in this study seem to suggest that it is possible to interrupt antifungal secondary prophylaxis of histoplasmosis, when the patient is clinically asymptomatic and the CD4+ cells counts are above 150 cells/microl.     

Prophylaxis of fungal infection in patients with hematologic neoplasms and severe neutropenia after high-dose chemotherapy]

Infection is one of the main causes of death in patients with hemoblastoses. Within the last years there was observed an increase in the ratio of fungal infections in the structure of mortality among hematologic patients with neutropenia. The present study was aimed at comparative estimation of the efficacy of the prophylactic use of various azole antifungal agents in patients with hematologic neoplasms and severe neutropenia. The trial enrolled 88 patients comparable by the diagnosis and chemotherapy characteristics, in whom severe neutropenia developed after intensive therapy. Antifungal drugs were used prophylactically when the neutrophil count lowered below 1.0 x 10(9)/l until its increasing above 1.0 x 10(9)/l or when the signs of fungal infection were evident. Itraconazole was used in cyclodextrin solution in 30 patients in a dose of 0.2 g orally twice a day and fluconazole was used in capsules in 24 patients in a dose of 0.2 g orally once a day. The results were compared with those of the ketoconazole use in a dose of 0.2 g orally twice a day (n = 34). The frequency of fungal infection proved by the clinical documentation was 20.5% in the ketoconazole group (k) (7 out of 34 patients), 8.3% in the fluconazole group (f) (2 out of 24 patients) and 6.6% in the itraconazole group (i) (2 out of 30 patients), p (k-f) = 0.21, p (k-i) = 0.11 and p (f-i) = 0.74. The frequency of fungal infection proved by the microbiological documentation was statistically much higher in the ketoconazole group (38.2%) vs. the fluconazole group (8.3%) (p = 0.013) and the itraconazole group (6.6%) (p = 0.004). The prophylactic use of itraconazole and fluconazole was efficient in preventing development of invasive mycoses in the patients with hemoblastoses and severe neutropenia. Their efficacy was much higher than that of ketoconazole.     

1株多重耐药申克孢子丝菌感染的治疗

报道1例由多重耐药申克孢子丝菌引起的面部孢子丝菌病。患者61岁男性,面部皮疹2 a余,先后口服伊曲康唑、特比萘芬和氟康唑治疗16个月无效。患者皮损经真菌镜检和培养确诊为孢子丝菌病,分离的申克孢子丝菌体外药敏试验显示其菌丝相和酵母相对上述三种药物均不敏感。给予患者口服10%碘化钾溶液治疗3个月获得痊愈。     

Isolated Skull Cryptococcosis in an Immunocompetent Patient

A 62-year-old immunocompetent rural woman who represents an isolated cryptococcal skull infection without systematic involvement is described. Diagnosis was based on positive India ink staining, positive histopathologic examination, and positive culture. Species identification was performed by growth on Sabouraud dextrose agar and CHROMagar medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. This case describes a rare presentation of Cryptococcus neoformans infection in a human immunodeficiency virus-negative patient. The lesions were significantly improved with treatment of daily oral itraconazole 400 mg. A maintenance therapy with a low-dose itraconazole was prescribed to warrant a clinical and mycological eradication. A two-year follow-up did not show any recurrence of infection.     

复发性外阴阴道假丝酵母菌病菌种分型及药敏

目的对RVVC、VVC患者阴道分泌物进行培养、菌种分型及药物敏感试验,探讨RVVC发生的原因。方法用沙保弱琼脂培养基培养阴道分泌物,分离纯化菌株;VITEK 2全自动微生物分析仪鉴定菌种;同时进行药物敏感试验。结果共分离出101株假丝酵母菌,其中RVVC组45株,VVC组51株,健康组5株。101株中白色假丝酵母菌86株,占85.1%(86/101),RVVC组45株中35株为白色假丝酵母菌,占77.8%(35/45);VVC组51株中47株为白色假丝酵母菌,占92.2%(47/51),健康组5株中4株为白色假丝酵母菌,占80%(4/5)。RV-VC组非白色假丝酵母菌比例高,与VVC组比较差异有显著性(P<0.05)。RVVC组假丝酵母菌对唑类药物敏感性低于VVC组。结论VVC、RVVC的主要致病菌仍是白色假丝酵母菌,RVVC组非白色假丝酵母菌比例高于VVC组。RVVC组假丝酵母菌对氟康唑的敏感率明显低于VVC组。     

R 51211 (itraconazole) therapy of murine cryptococcosis

A new antifungal triazole, itraconazole (R51211), was compared with ketoconazole in treatment of murine cryptococcosis. Itraconazole is sparingly soluble in water, and must be administered orally in solvents such as polyethylene glycol. Serum concentrations are lower than those achieved with ketoconazole, but sustained for longer periods. Itraconazole was more effective than ketoconazole by MIC, but was similar to ketoconazole by minimum fungicidal concentration. Both drugs prolonged equally survival after intraperitoneal or intracerebral challenge with Cryptococcus neoformans. Tissue counts of C. neoformans were similar in mice treated with either drug. Neither drug sterilized brains of mice challenged intracerebrally. Itraconazole appears equally potent as ketoconazole, but in this model does not appear to offer any therapeutic advantage over ketoconazole.     

Fonsecaea monophora所致着色芽生菌病1例及其相关实验研究

目的 报道1例由Fonsecaea monophora所致的着色芽生菌病.方法 患者女,60岁,主因左手背皮损1 a余就诊,取皮损痂屑进行真菌直接镜检和培养,取皮损组织进行组织病理学检查和真菌培养.对培养获得菌株进行形态学和分子生物学鉴定,并进行药物敏感性检测.结果 真菌直接镜检阳性,可见较多圆形、厚壁、棕色的硬壳细胞.组织病理学显示为慢性肉芽肿样改变;HE和PAS染色均可见到圆形、厚壁、棕色的硬壳细胞.真菌培养阳性,菌落生长缓慢,呈橄榄色到黑色.小培养及扫描电镜检查可见枝孢型和喙枝孢型产孢,分生孢子单细胞性,呈椭圆形或卵圆形.ITS区序列分析鉴定为Fonsecaea monophora.药敏试验显示伊曲康唑对F.monophora的最低抑菌浓度（minimal inhibitory concentration,MIC）为1.0 μg/mL,特比萘芬的MIC为0.015 6μg/mL.给予患者口服特比萘芬250 mg/d治疗,皮损缓慢好转;6周后加服伊曲康唑200 mg/d治疗,14周后皮损消退呈瘢痕化修复.结论 依据临床及实验室检查确诊该病例为Fonsecaeamonophora所致着色芽生菌病,伊曲康唑联合特比萘芬治疗本病例显示较好疗效.