• 【由于Fonsecaea pedrosoi引起的广泛的长期嗜铬病: 在伏立康唑治疗下有3例相关改善。】 复制标题 收藏 收藏
    DOI:10.3109/09546630903585074 复制DOI
    作者列表:Criado PR,Careta MF,Valente NY,Martins JE,Rivitti EA,Spina R,Belda W Jr
    BACKGROUND & AIMS: OBJECTIVE:To evaluate voriconazole in the treatment of extensive cases of chromomycosis. Chromomycosis is a chronic infection, which is extremely difficult to eradicate, and is caused by dematiaceous (dark-colored) fungi which affect the skin and subcutaneous tissues, with Fonsecaea pedrosoi being the major etiologic agent. Drugs such as itraconazole, terbinafine, posaconazole and amphotericin B have been employed with variable results. METHODS:We treated three Caucasian male patients (ages 44, 57 and 77 years), two were farmers and one a trash collector, with long-standing (20, 10 and 21 years of disease, respectively) and extensive chromomycosis (one lower limb affected, at least) due to Fonsecaea pedrosoi. All patients had received previous therapy with the formerly indicated drugs itraconazole and terbinafine for several months either without or with incomplete response. After that, we started treatment with voriconazole per os 200 mg twice a day. RESULTS:The patients were treated with voriconazole for 12 months until there was clinical and mycological improvement. Clinical response was evident after 30-50 days. One patient developed visual abnormalities and tremors, and the voriconazole was reduced to 200 mg/day without impairment of the clinical and mycological response. The same patient presented photosensitive dermatitis after 12 months of therapy and the voriconazole was stopped. All patients showed elevations of serum gamma-glutamyl transpeptidase (GGT) during the treatment without clinical relevance. Moreover, our three patients obtained partial response with this therapy. CONCLUSIONS:This is the first report with a case series of chromomycosis treated with voriconazole. Despite its high cost, voriconazole is a safe and possibly promising drug for use on extensive chromomycosis refractory to conventional treatment.
    背景与目标:
  • 【在伏立康唑治疗下,阿萨希毛孢菌对急性髓系白血病患者的致命播散性感染: 毛孢菌菌属突破性感染的综述。】 复制标题 收藏 收藏
    DOI:10.1007/s11046-019-00416-w 复制DOI
    作者列表:Ramírez I,Moncada D
    BACKGROUND & AIMS: INTRODUCTION:Cases of invasive Trichosporon infections have increasingly emerged; it is now the second leading cause of yeast bloodstream infections after Candida spp., particularly in the immunosuppressed population, where it often causes breakthrough fungemia with high mortality. METHODS:We present a case report of a breakthrough Trichosporon asahii infection in a patient with acute myeloid leukemia and review all of the cases of breakthrough Trichosporon spp. infections published in the literature to date. RESULTS:We extracted 68 cases of breakthrough Trichosporon spp. infections, wherein 95.5% patients had hematological malignancy, 61.8% of them occurred in the presence of echinocandins, 22% of triazoles, 13.2% of amphotericin and 3% of other combinations of antifungals. The most prevalent manifestation was fungemia (94%); 82.8% of these were associated with the presence of a central venous catheter. The overall mortality was 68.7%; the patients who survived recovered from the neutropenic event. CONCLUSIONS:Invasive trichosporonosis is an acute fatal condition that occurs in immunosuppressed patients, usually under antifungal selective pressure. Typically, neutropenia and its underlying diseases are associated with adverse outcomes.
    背景与目标:
  • 【伏立康唑或伊曲康唑与其他抗真菌剂对镰刀菌的协同作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.riam.2013.01.002 复制DOI
    作者列表:Spader TB,Venturini TP,Rossato L,Denardi LB,Cavalheiro PB,Botton SA,Santurio JM,Alves SH
    BACKGROUND & AIMS: BACKGROUND:Infections caused by Fusarium are difficult to treat because these fungi show in vitro and in vivo resistance to practically all the antifungal agents available, which explains the high mortality rates. An attempt to overcome fungal resistance is the combination of antifungal agents, especially those with different mechanisms of action. AIMS:Evaluate the in vitro interactions of combinations of voriconazole or itraconazole with other antifungal agents against 32 isolates of Fusarium spp.: Fusarium chlamydosporum, Fusarium oxysporum, Fusarium proliferatum and Fusarium solani. METHODS:Drug interactions were assessed by a checkerboard microdilution method that also included the determination of the MIC of each drug alone according to CLSI (Clinical and Laboratory Standards Institute) document M38-A2, 2008. RESULTS:The best combinations were voriconazole+terbinafine which showed synergism against 84% of Fusarium strains. Other synergistic combinations were voriconazole+itraconazole (50%), voriconazole+fluconazole (50%), voriconazole+miconazole (38%), voriconazole+flucytosine (22%) and voriconazole+ketoconazole (25%). The synergisms observed with itraconazole combinations were itraconazole+terbinafine (25%) and itraconazole+flucytosine (9.37%). The antagonisms observed were: voriconazole+fluconazole (3%) and itraconazole+flucytosine (12.5%). CONCLUSIONS:The synergism showed by voriconazole+terbinafine was remarkable. To better elucidate the potential usefulness of our findings, new in vivo and in vitro studies deserve be performed.
    背景与目标:
  • 【在急性骨髓性白血病或骨髓增生异常综合征的诱导治疗中,泊沙康唑与伏立康唑作为抗真菌预防。】 复制标题 收藏 收藏
    DOI:10.1177/1078155218806975 复制DOI
    作者列表:Phillips K,Cirrone F,Ahuja T,Siegfried J,Papadopoulos J
    BACKGROUND & AIMS: OBJECTIVE:Patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing induction chemotherapy are at increased risk of invasive fungal infection due to prolonged, severe neutropenia. Due to this risk, national guidelines recommend invasive fungal infection prophylaxis in this population until the resolution of neutropenia. Although posaconazole has demonstrated superiority over fluconazole and itraconazole, there is limited evidence for voriconazole for invasive fungal infection prophylaxis in this population. Even less data are available comparing posaconazole and voriconazole directly. The study objective was to investigate the efficacy and safety of delayed-release posaconazole tablets versus voriconazole for primary invasive fungal infection prophylaxis. The primary outcome was rate of discontinuation of either agent. Secondary outcomes included specific rates of discontinuation due to adverse events and drug-drug interactions, rates of breakthrough invasive fungal infection, and 30-day and 100-day mortality rates. METHODS:This was a retrospective cohort study of adult patients admitted to NYU Langone Health between 1 January 2014 and 31 August 2017 and initiated on invasive fungal infection prophylaxis during induction or reinduction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. RESULTS:In total, 77 patients were included in the study: 43 using posaconazole delayed-release tablets and 34 using oral voriconazole. In the posaconazole group, 30% of patients (n = 13) discontinued therapy for any reason compared with 35% (n = 12) of patients in the voriconazole group (p = 0.64). A higher percentage of patients in the voriconazole group discontinued due to adverse events (6 patients, 18% vs. 1 patient, 2%, p = 0.04). Mortality rates at 30 and 100 days were similar between both groups. No breakthrough invasive fungal infections was noted in either group. CONCLUSION:Overall, discontinuations for any reason were similar in patients taking both posaconazole delayed-release and oral voriconazole. Both posaconazole delayed-release tablets and oral voriconazole appear to be effective at preventing invasive fungal infection in acute myelogenous leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy, although posaconazole may be more tolerable.
    背景与目标:
  • 【肥胖和超重免疫功能低下患者的伏立康唑血清浓度: 一项回顾性研究。】 复制标题 收藏 收藏
    DOI:10.1002/phar.1156 复制DOI
    作者列表:Davies-Vorbrodt S,Ito JI,Tegtmeier BR,Dadwal SS,Kriengkauykiat J
    BACKGROUND & AIMS: STUDY OBJECTIVE:To evaluate the relationship between voriconazole dose and corresponding serum concentrations in obese and overweight immunocompromised patients. DESIGN:Retrospective medical record review. SETTING:National Cancer Institute-designated comprehensive cancer center. PATIENTS:A total of 92 patients with hematologic malignancies and/or hematopoietic stem cell transplants who received voriconazole and had reported steady-state serum concentrations (peak, random, or trough) during 2005-2010; 124 serum concentrations were available for analysis. MEASUREMENTS AND MAIN RESULTS:Data on patient demographics, voriconazole concentrations, and other clinical and safety data were collected. Patients were stratified based on body mass index (BMI). Patients with higher BMIs tended to have significantly higher median random voriconazole concentrations with intravenous administration (6.4 mg/L for BMI ≥ 25 kg/m(2) vs 2.8 mg/L for BMI < 25 kg/m(2), p=0.04). This trend was more notable with the intravenous than the oral formulations. With the oral formulation, patients with a BMI of 25 kg/m(2) or greater had a median random concentration of 2.8 mg/L compared with 2.0 mg/L in patients with a BMI less than 25 kg/m(2) (p=0.18). Patients with a BMI of 25 kg/m(2) or greater also had a higher median daily voriconazole dose (640 vs 400 mg, p<0.001). No significant differences were noted in factors that would affect oral absorption of voriconazole (e.g., graft-versus-host disease) among BMI groups. When comparing all voriconazole concentrations, higher concentrations were associated with a greater percentage of patients who had alanine aminotransferase levels of more than 3 times the upper limit of normal. Patients with voriconazole random concentrations of 2 mg/L or greater had higher response rates (50%) than patients with concentrations lower than 2 mg/L (33%). CONCLUSION:Standard voriconazole dosing using actual body weight in obese and overweight patients resulted in higher associated serum concentrations. Dosing using adjusted body weight may be necessary in this population in order to achieve optimal concentrations while preventing the potential for increased toxicity.
    背景与目标:
  • 【局部伏立康唑是否会触发眼表发育异常改变?】 复制标题 收藏 收藏
    DOI:10.1179/1973947814Y.0000000166 复制DOI
    作者列表:Palamar M,Egrilmez S,Yilmaz SG,Polat SH,Gunduz OU
    BACKGROUND & AIMS: PURPOSE:Systemic voriconazole treatment was reported to cause photosensitivity and related cutaneous malignancies. The aim of this report is to demonstrate a graft-related Candida endophthalmitis case that developed ocular surface dysplastic changes after receiving topical 1% voriconazole treatment. METHODS:Full ocular examination, photography, and in vivo confocal microscopy examination (Rostock Cornea Module/HRT II, Heidelberg, Germany) were performed. RESULTS:A 73-year-old male with graft-related Candida endophthalmitis that was on topical 1% voriconazole for 4 months developed a whitish gelatinous lesion on the cornea originating from the nasal limbus. In vivo confocal microscopy examination revealed mild dysplastic changes in the cornea epithelium. CONCLUSION:Topical voriconazole might trigger neoplastic changes on the ocular surface as reported with systemic use in other sun-exposed parts of the body. Further studies are needed to relate topical use of voriconazole with ocular surface dysplasia.
    背景与目标:
  • 【基于氟达拉滨的脐血移植后,伏立康唑对侵袭性真菌病进行初步预防的前瞻性可行性研究。】 复制标题 收藏 收藏
    DOI:10.1007/s12185-014-1529-7 复制DOI
    作者列表:Takagi S,Araoka H,Uchida N,Uchida Y,Kaji D,Ota H,Nishida A,Ishiwata K,Tsuji M,Yamamoto H,Ito T,Matsuno N,Yamamoto G,Asano-Mori Y,Hayashi M,Izutsu K,Masuoka K,Wake A,Makino S,Yoneyama A,Taniguchi S
    BACKGROUND & AIMS: :Despite the recent introduction of a new class of anti-Aspergillus agents, no standard regimen for the prevention of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation has been shown to be superior to fluconazole. The present prospective, single-arm study investigated the feasibility of voriconazole (VOR) administration as primary prophylaxis in 52 recipients of umbilical cord blood transplantation (CBT) with fludarabine-based conditioning, who had no previous IFD episodes. Proven or probable IFD was determined using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were considered as breakthrough infections. VOR was administered as prophylaxis for a total of 6884 patient-days following CBT. The mean duration of VOR administration after transplantation was 132 days (range, 1-769); 44 patients (85 %) had advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %) received systemic corticosteroid therapy for allogeneic immune-mediated complications. Under the prophylaxis with VOR, one patient developed probable invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 % at day 180. None of the patients developed breakthrough candida or zygomycetes infections. Under the extensive therapeutic dose monitoring, VOR was safely administered with a calcineurin inhibitor and was well tolerated. These results suggest that VOR represents a feasible primary prophylactic agent for IFD after CBT with fludarabine-based conditioning.
    背景与目标: : 尽管最近引入了一种新型的抗曲霉菌药,但尚无用于预防异基因造血干细胞移植后侵袭性真菌病 (IFD) 的标准方案优于氟康唑。目前的前瞻性单臂研究调查了在52名以前没有IFD发作的基于氟达拉滨的脐带血移植 (CBT) 接受者中使用伏立康唑 (VOR) 作为主要预防的可行性。使用欧洲癌症/侵袭性真菌感染研究与治疗组织合作小组确定了已证实或可能的IFD,而美国国家过敏和传染病研究所Mycoses研究小组 (EORTC/MSG) 标准被认为是突破性感染。在CBT后总共6884个患者日给予VOR作为预防。移植后VOR给药的平均持续时间为132天 (范围,1-769天); 44例患者 (85% 例) 患有晚期疾病,15例 (29% 例) 有同种异体HSCT病史,29例 (56% 例) 因同种异体免疫介导的并发症接受全身性皮质类固醇治疗。在VOR的预防下,一名患者在第71天发生了可能的侵袭性曲霉病,并且在第180天4.5% 了IFD的累积发生率。没有患者出现突破性的念珠菌或接合菌感染。在广泛的治疗剂量监测下,VOR与钙调神经磷酸酶抑制剂一起安全给药,并且耐受性良好。这些结果表明,在使用基于氟达拉滨的CBT调理后,VOR代表了IFD的可行的主要预防剂。
  • 【伏立康唑治疗难治性烟曲霉角膜炎。】 复制标题 收藏 收藏
    DOI:10.4103/0301-4738.40369 复制DOI
    作者列表:Mehta H,Mehta HB,Garg P,Kodial H
    BACKGROUND & AIMS: :We report a case of Aspergillus fumigatus keratitis in a 53-year-old, well-controlled diabetic female who did not respond to standard antifungal treatment. She was started on topical natamycin eye drops, but the infiltrate continued to progress. Topical amphotericin B and systemic ketoconazole was added, however, there was no response and the infiltrate increased further. She was then switched to topical and systemic voriconazole. Steady resolution of the infiltrate was noted within 2 weeks of therapy.
    背景与目标: : 我们报告了一名53岁,控制良好的糖尿病女性的烟曲霉性角膜炎病例,该女性对标准抗真菌治疗无反应。她开始使用局部纳他霉素滴眼液,但浸润持续进展。局部添加两性霉素b和全身性酮康唑,但无反应,浸润进一步增加。然后改用外用和全身性伏立康唑。治疗后2周内发现浸润稳定消退。
  • 【在日本人群中,视觉障碍与伏立康唑引起的幻觉合并症。】 复制标题 收藏 收藏
    DOI:10.1007/s12185-008-0114-3 复制DOI
    作者列表:Imataki O,Ohnishi H,Kitanaka A,Kubota Y,Ishida T,Tanaka T
    BACKGROUND & AIMS: :Voriconazole (VRCZ) has a curious visual adverse event that is completely reversible, but its mechanism has not been fully addressed. We observed 20 consecutive patients treated with VRCZ after chemotherapy for hematological malignancy. Six of these cases experienced visual disturbance, and all cases among those treated with oral VRCZ. The authors discuss a relatively higher frequency of visual events complicated with hallucination, which might be associated with a special metabolism of VRCZ in Japanese patients with hematological malignancies. Hallucination and oral administration were specific clinical features for the patients presenting with visual adverse events in response to VRCZ.
    背景与目标: : 伏立康唑 (VRCZ) 具有完全可逆的视觉不良事件,但其机制尚未得到充分解决。我们观察了20例连续化疗后接受VRCZ治疗的血液恶性肿瘤患者。这些病例中有6例出现视觉障碍,所有病例均接受口服VRCZ治疗。作者讨论了相对较高的视觉事件并发幻觉的频率,这可能与日本血液系统恶性肿瘤患者的VRCZ的特殊代谢有关。幻觉和口服给药是针对VRCZ出现视觉不良事件的患者的特定临床特征。
  • 【2011年高危患者101例侵袭性毛霉菌病的累积发病率,严重程度和死亡率的稳定性: 伏立康唑和棘白霉素-两性霉素c使用前后的eras比较】 复制标题 收藏 收藏
    DOI:10.1111/myc.12222 复制DOI
    作者列表:Abidi MZ,Sohail MR,Cummins N,Wilhelm M,Wengenack N,Brumble L,Shah H,Jane Hata D,McCullough A,Wendel A,Vikram HR,Kusne S,Litzow M,Letendre L,Lahr BD,Poeschla E,Walker RC
    BACKGROUND & AIMS: :As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.
    背景与目标: : 随着侵袭性毛霉菌病 (IM) 数量的增加,临床医生怀疑先前的伏立康唑会加重IM的发生率和严重程度,并相信联合抗真菌治疗可提高IM的生存率。为了比较在伏立康唑商业上市之前和之后的eras中IM的累积发生率 (CI),严重程度和死亡率,分析了四个风险组 (血液/肿瘤恶性肿瘤 (H/O),干细胞移植 (SCT)) 1995年2011年的所有IM病例,实体器官移植 (SOT) 等),和两个eras,E1 (1995-2003) 和E2 (2004-2011)。在101例IM病例中,(79例证实,22例可能): 30例为E1 (3.3/年),71例为E2 (8.9/年)。在era之间,H/O或SCT的比例从47% 上升到73%,而 “其他” 从33% 下降到11% (P = 0.036)。在eras之间,IM的CI在SCT (P = 0.27) 或SOT (P = 0.30) 中没有显着增加,并且解剖位置 (P = 0.122) 和手术清创 (P = 0.200) 的模式相似。在E2中,接受两性霉素-棘皮素联合治疗的患者明显更多 (31% vs. 5%,P = 0.01); 然而,90天生存率没有改善 (54% vs. 59%,P = 0.67)。自2003以来,IM的上升反映了越来越多的风险,而不是以前使用伏立康唑。经常联合抗真菌治疗并不能提高生存率。
  • 【Uplc-ms/MS测定人血浆中伏立康唑的含量及其在药代动力学研究中的应用。】 复制标题 收藏 收藏
    DOI:10.1002/bmc.3257 复制DOI
    作者列表:Wang Z,Huang CK,Sun W,Xiao C,Wang ZS
    BACKGROUND & AIMS: :A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine voriconazole in human plasma. Sample preparation was accomplished through a simple one-step protein precipitation with methanol. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of acetonitrile and water containing 1% formic acid (45:55, v/v) at a flow rate of 0.50 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 351.0 → 281.5 and m/z 237.1 → 194.2 were used to quantify voriconazole and carbamazepine (internal standard), respectively. The linearity of this method was found to be within the concentration range of 2.0-1000 ng/mL with a lower limit of quantification of 2.0 ng/mL. Only 1.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after oral administration of 200 mg voriconazole to 20 Chinese healthy male volunteers.
    背景与目标: : 建立了一种灵敏,快速的超高效液相色谱串联质谱法 (uplc-ms/MS) 测定人血浆中伏立康唑的方法。样品制备是通过用甲醇进行简单的一步蛋白沉淀来完成的。色谱分离在Acquity uplcbehc18柱上使用由乙腈和含有1% 甲酸 (45:55,v/v) 的水组成的等度流动相系统以0.50  mL/min的流速进行。使用QTrap5500质谱仪与正离子模式的电喷雾电离源结合进行质谱分析。m/z 351.0  →   281.5和m/z 237.1  →   194.2的多反应监测转换分别用于定量伏立康唑和卡马西平 (内标)。发现该方法的线性范围在2.0-1000  ng/mL的浓度范围内,定量下限为2.0  ng/mL。分析运行只需要1.0  min。经充分验证的方法成功应用于20名中国健康男性志愿者口服伏立康唑200  mg后的药代动力学研究。
  • 12 [Hallucinosis as side effect of voriconazole]. 复制标题 收藏 收藏

    【[幻觉作为伏立康唑的副作用]。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-2565(05)72663-1 复制DOI
    作者列表:Flox Benítez G,Rondón Fernández P,Quero Escalada M,Fernández Ballesteros A
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【辉瑞公司伏立康唑抗真菌试验的设计,分析和解释方面的缺陷以及不加批评的后续报价。】 复制标题 收藏 收藏
    DOI:10.1186/1745-6215-7-3 复制DOI
    作者列表:Jørgensen KJ,Johansen HK,Gøtzsche PC
    BACKGROUND & AIMS: :We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before.
    背景与目标: : 我们之前已经描述了由辉瑞公司赞助的抗真菌药物氟康唑在患有中性粒细胞减少症的癌症患者中的一系列试验如何通过设计和分析中的缺陷来限制对照药物两性霉素b。我们在辉瑞新型抗真菌剂伏立康唑的两项关键试验中描述了类似的问题,该试验发表在著名杂志上。在一项非劣效性试验中,伏立康唑明显低于两性霉素b脂质体,但作者得出结论,伏立康唑是合适的替代品。第二项试验使用了两性霉素b脱氧胆酸盐作为比较剂,但由于不需要预先用药以减少与输注相关的毒性或用电解质和液体替代以减少肾毒性,从而限制了药物的使用,尽管计划的治疗时间为84天。伏立康唑平均给药77天,但比较药仅给药10天,因此无法进行有意义的比较。在对这些试验的50个参考文献的随机样本中,我们发现不必要的结论大多是不加批判地传播的。尤其令人惊讶的是,FDA提出的与第一项试验有关的相关批评只被引用了一次,而且没有一篇文章注意到第二项试验设计中的明显缺陷。我们建议编辑确保摘要公平地反映在论文的其余部分上,并且期刊不要对接受指出研究中严重弱点的信件施加任何时间限制,这些信件指出了以前没有注意到的问题。
  • 【伏立康唑最佳血药浓度的调查和阈值: 一项描述性统计荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1007/s10156-011-0363-6 复制DOI
    作者列表:Hamada Y,Seto Y,Yago K,Kuroyama M
    BACKGROUND & AIMS: :Voriconazole (VRCZ) reportedly possesses a broad spectrum of antifungal activity against Aspergillus spp. and Candida spp., and the blood concentration of VRCZ is correlated with both the efficacy and the adverse effects of this drug. Monitoring of the blood concentration target level of VRCZ has not yet been widely adopted in the medical field, and no evidence concerning this target level has been reported. Accordingly, we used a meta-analysis to investigate the optimal blood concentration of VRCZ. Using data from 12 reports, we found that the success rate for fungal infection treatment increased significantly at VRCZ levels greater than 1.0 μg/ml when a graded cutoff value within the range of 1.0-3.0 μg/ml was used as the VRCZ trough blood concentration [odds ratio (OR) 7.23, 95% confidence interval (CI) 2.84-18.37, P < 0.0001]. Concerning the safety evaluation, the incidence of adverse neurological effects increased significantly at a cutoff value of 4.0 μg/ml when a graded cutoff value within the range of 3.0-6.0 μg/ml was used (OR 2.23, 95% CI 1.12-4.46, P = 0.02). However, in all 12 literature sources, an increasing incidence of liver dysfunction was reported at higher blood concentrations, and no accurate cutoff values were obtained. Consequently, a VRCZ trough blood concentration more than 1.0 μg/ml from the perspective of efficacy and less than 4.0 μg/ml from the perspective of safety is recommended.
    背景与目标: : 据报道,伏立康唑 (VRCZ) 对曲霉属具有广泛的抗真菌活性。和念珠菌属,VRCZ的血药浓度与该药物的疗效和不良反应均相关。监测VRCZ的血药浓度目标水平尚未在医学领域得到广泛采用,也没有关于该目标水平的证据报道。因此,我们使用荟萃分析来研究VRCZ的最佳血液浓度。使用来自12份报告的数据,我们发现,当使用1.0-3.0 μ g/ml范围内的分级截止值作为VRCZ谷血药浓度 [优势比 (OR) 7.23时,在VRCZ水平大于1.0 μ g/ml时,真菌感染治疗的成功率显着提高,95% 置信区间 (CI) 2.84-18.37,P <0.0001]。关于安全性评估,当使用3.0-6.0 μ g/ml范围内的分级截止值 (或2.23,95% CI 1.12-4.46,P = 0.02) 时,在4.0 μ g/ml的截止值下,神经系统不良反应的发生率显着增加。然而,在所有12个文献来源中,在较高的血药浓度下,肝功能异常的发生率增加,并且未获得准确的截止值。因此,建议从功效的角度来看VRCZ谷血药浓度大于1.0 μ g/ml,从安全性的角度来看小于4.0 μ g/ml。
  • 【肉汤微量稀释和圆盘扩散方法对卡泊芬净,伏立康唑,两性霉素b,伊曲康唑和氟康唑对光滑念珠菌的抗真菌药敏试验的相关性。】 复制标题 收藏 收藏
    DOI:10.1016/j.mimet.2010.05.002 复制DOI
    作者列表:Kiraz N,Dag I,Oz Y,Yamac M,Kiremitci A,Kasifoglu N
    BACKGROUND & AIMS: :Candida glabrata is one of the most frequent organisms isolated from superficial and invasive fungal infections, after Candida albicans. This organism also exhibits intrinsically low susceptibility to azole antifungals and treatment often fails. The microdilution method is not very practical for use in routine susceptibility testing in the clinical laboratory, thus necessitating the use of other methods. In this study, we compared the in vitro activity of five antifungal agents in three different groups (echinocandin, polyene and azole) against 50 C. glabrata isolates by broth microdilution and disk diffusion methods recommended by Clinical Laboratory Standards Institute CLSI M27-A3 and CLSI M44-A, respectively. All the isolates were susceptible to amphotericin B (100%) and 98% of the isolates were susceptible to caspofungin by the broth microdilution method. Within the azole group drugs, voriconazole was the most active followed by fluconazole and itraconazole in vitro. The highest rate of resistance was obtained against itraconazole with a high number of isolates defined as susceptible-dose dependent or resistant. Although the disk diffusion method is easy to use in clinical laboratories, it shows very poor agreement with the reference method for fluconazole and itraconazole against C. glabrata (8% and 14%, respectively).
    背景与目标: : 光滑念珠菌是继白色念珠菌之后从浅表和侵袭性真菌感染中分离出来的最常见的生物之一。这种生物对唑类抗真菌药的敏感性本质上也较低,并且治疗通常失败。微量稀释法在临床实验室的常规药敏试验中使用不是很实用,因此需要使用其他方法。在这项研究中,我们通过临床实验室标准研究所CLSI M27-A3和CLSI M44-A推荐的肉汤微量稀释和纸片扩散方法,比较了三种不同组 (棘皮菌素,多烯和唑) 对50种无毛念珠菌的体外活性。通过肉汤微量稀释法,所有分离株均对两性霉素b (100%) 敏感,98% 分离株对卡泊芬净敏感。在唑类药物中,伏立康唑是最活跃的,其次是氟康唑和伊曲康唑。对伊曲康唑的耐药率最高,其中大量分离株被定义为敏感剂量依赖性或耐药性。尽管纸片扩散法易于在临床实验室中使用,但与氟康唑和伊曲康唑对光滑C的参考方法 (分别为8% 和14%) 的一致性很差。

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