BACKGROUND & AIMS: :We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man who underwent retinal detachment surgery consecutive to a penetrating globe injury presented with endophthalmitis 7 days after surgery. Anterior chamber tap and intravitreal injection of antibiotics (ceftazidime and vancomycin) were performed systematically. Fungus was observed at microscopic examination of the aqueous humor and treatment with intravitreal injection of amphotericin B was decided. The patient failed to improve with intravitreal amphotericin B but responded clinically to intravitreal voriconazole. The fungus was identified after culture as Phoma glomerata. The MIC for amphotericin B was 1microg/ml, for caspofungin was 2microg/ml, and for itraconazole was 8microg/ml or more. The MIC for voriconazole was up to 8microg/ml. The clinical response after intravitreal injection may be related to the high concentrations reached in the vitreous. Because of severity and ominous prognosis of intraocular fungal infections and posttraumatic Phoma ocular infections, aggressive management is required by intravitreal voriconazole administration.

背景与目标： : 我们报告了第一例由肾小球淋巴瘤引起的眼内炎。一名32岁的男子在手术后7天连续接受视网膜脱离手术，导致穿透性球部受伤，并出现眼内炎。系统地进行前房敲击和玻璃体内注射抗生素 (头孢他啶和万古霉素)。在房水的显微镜检查中观察到真菌，并确定玻璃体内注射两性霉素b进行治疗。患者玻璃体内两性霉素b未能改善，但对玻璃体内伏立康唑有临床反应。培养后将真菌鉴定为肾小球真菌。两性霉素b的MIC为1 μ g/ml，卡泊芬净为2 μ g/ml，伊曲康唑为8 μ g/ml以上。伏立康唑的MIC高达8微克/毫升。玻璃体内注射后的临床反应可能与玻璃体中达到的高浓度有关。由于眼内真菌感染和创伤后眼部感染的严重程度和不良预后，玻璃体内伏立康唑需要积极治疗。

BACKGROUND & AIMS: :The development of novel antifungal agents with high susceptibility and increased potency can be achieved by increasing their overall lipophilicity. To enhance the lipophilicity of voriconazole, a second generation azole antifungal agent, we have synthesized its carboxylic acid ester analogues, namely p-methoxybenzoate (Vpmb), toluate (Vtol), benzoate (Vbz) and p-nitrobenzoate (Vpnb). The intermolecular interactions of these analogues with model membrane have been investigated using nuclear magnetic resonance (NMR) and differential scanning calorimetric (DSC) techniques. The results indicate varying degree of changes in the membrane bilayer's structural architecture and physico-chemical characteristics which possibly can be correlated with the antifungal effects via fungal membrane. Rapid metabolite profiling of chemical entities using cell preparations is one of the most important steps in drug discovery. We have evaluated the effect of synthesized analogues on Candida albicans. The method involves real time (1)H NMR measurement of intact cells monitoring NMR signals from fungal metabolites which gives Metabolic End Point (MEP). This is then compared with Minimum Inhibitory Concentration (MIC) determined using conventional methods. Results indicate that one of the synthesized analogues, Vpmb shows reasonably good activity.

背景与目标： : 可以通过提高其总体亲脂性来开发具有高敏感性和增强效力的新型抗真菌剂。为了增强第二代唑类抗真菌剂伏立康唑的亲脂性，我们合成了其羧酸酯类似物，即对甲氧基苯甲酸酯 (Vpmb)，甲苯酸酯 (Vtol)，苯甲酸酯 (Vbz) 和对硝基苯甲酸酯 (Vpnb)。已使用核磁共振 (NMR) 和差示扫描量热法 (DSC) 技术研究了这些类似物与模型膜的分子间相互作用。结果表明，膜双层的结构和理化特性发生了不同程度的变化，这可能与真菌膜的抗真菌作用有关。使用细胞制剂对化学实体进行快速代谢物分析是药物发现中最重要的步骤之一。我们已经评估了合成类似物对白色念珠菌的影响。该方法涉及对完整细胞进行实时 (1)H NMR测量，以监测来自真菌代谢物的NMR信号，从而给出代谢终点 (MEP)。然后将其与使用常规方法确定的最小抑制浓度 (MIC) 进行比较。结果表明，合成的类似物之一Vpmb具有相当好的活性。

BACKGROUND & AIMS: Background:Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined. Objectives:To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion. Methods:Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P  <   0.05) reduction in fungal burden in brain. Results:A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%. Conclusions:CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Voriconazole is extensively metabolized by the CYP450 isoenzymes 2C19 and 3A4 and to a lesser extent by CYP2C9; therefore, any medication that affects this pathway can alter its plasma concentration. Treatment failure can probably occur if subtherapeutic levels are achieved. CASE DESCRIPTION:A 32-year-old woman who suffered from acute lymphoblastic leukemia was admitted and received treatment with vincristine and dexamethasone. After several days, to control her fever, based on two consecutive positive serum galactomannan test results, voriconazole as an antifungal agent was added to Aspergillus infection treatment. Through the first week after voriconazole initiation, its plasma concentrations were subtherapeutic. The most suspicious medication for interaction was dexamethasone, which can induce CYP450 isoenzymes and reduce plasma concentration. CONCLUSION:As a result of the narrow therapeutic window of voriconazole and the relationship between efficacy and plasma concentration of azoles, therapeutic drug monitoring of voriconazole in patients receiving a high dose of glucocorticoids is recommended, in order to achieve optimal response to treatment and toxicity reduction. Further studies regarding the interaction between voriconazole and dexamethasone to prevent clinically relevant interactions should be considered.

背景与目标：

BACKGROUND & AIMS: Importance:The antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). Objective:To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. Design, Setting, and Participants:This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019. Exposures:Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. Main Outcomes and Measures:Primary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. Results:Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). Conclusions and Relevance:In this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

背景与目标：

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：

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：

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：

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：

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：

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：

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。

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。

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。

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。