Photodynamic therapy-mediated hypericin-loaded nanostructured lipid carriers against vulvovaginal candidiasis

Introduction and Aim: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). Materials and Methods: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. Results: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log₁₀ reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. Conclusion: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.     

Prevalence and species distribution of microorganisms isolated among non-pregnant women affected by vulvovaginal candidiasis: A retrospective study over a 20 year-period

BackgroundVulvovaginal candidiasis (VVC) is the second most common infection of the genital tract affecting millions of women worldwide. Data concerning the distribution and antifungal resistance of Candida species responsible of VVC vary among countries and population studied. Objectives: The aim of this work was to determine the prevalence, species distribution and antifungal susceptibility patterns of Candida species among symptomatic women over a 20-year period.MethodsA total of 5,820 unique samples were retrospectively identified. Out of them, 1,046 (18%) were diagnosed with VVC.ResultsWomen between 18 and 30 years had the highest prevalence rate of VVC (21%). Women aged less than 18 years and greater than 51 years had the highest prevalence rates of vaginal bacterial infections. Thirty-five (3.3%) women presented recurrent VVC. The most common yeast isolated was C. albicans, followed by C. glabrata, C. krusei, and C. parapsilosis. Non-Candida albicans species (NAC) were more significantly isolated among women aged 51 or above, than in women included in other groups (p < 0.01). Resistance to fluconazole and amphotericin B was infrequent in C. albicans strains. Resistance to fluconazole and amphotericin B was infrequent in C. albicans strains. NAC species presented higher resistance rates against fluconazole (30%) and voriconazole (25%). C. krusei and C. glabrata isolates showed lower MICs than most of the strains against amphotericin B (1 mg/L) and flucytosine (1 mg/L).ConclusionsOur findings indicated that continued surveillance on Candida species distribution and non-susceptibility rates to antifungals should be routinely reported to help the selection of the most appropriate drug, to avoid the emergence of resistant strains, and to improve the patient's outcomes.     

Posaconazole: a potent, extended-spectrum triazole anti-fungal for the treatment of serious fungal infections

Posaconazole is a potent, extended-spectrum, investigational triazole anti-fungal that is highly active in pre-clinical in vitro and in vivo models against a wide array of yeasts and moulds, including Aspergillus, Fusarium and Zygomycetes, which are often refractory to polyenes and older azoles. In humans, orally administered posaconazole is absorbed under fed or fasted conditions; however, absorption is significantly improved when it is coadministered with food or liquid nutritional supplements and when the daily dose is divided (into two or four daily doses). Unlike newer azoles, posaconazole is not extensively metabolised by cytochrome P450 (CYP) enzymes and is primarily excreted as parent compound in the faeces. Posaconazole is a CYP3A4 inhibitor, but it does not inhibit the activity of other CYP enzymes. Therefore, in comparison with other azole anti-fungal drugs, posaconazole may have the potential for fewer drug interactions. The pharmacokinetics of posaconazole are not influenced by age, gender or race. Dose adjustments for renal or hepatic impairment do not appear to be indicated based on results from single-dose studies. Preliminary efficacy data from clinical trials are promising. As salvage therapy, posaconazole elicited complete or partial responses in 44 to 75% of patients (N = 97) with invasive fungal infections who were intolerant of, or who had disease refractory to, amphotericin B or itraconazole. In an analysis of patients with aspergillosis, a 42% success rate was observed in the posaconazole arm (n = 107) compared with a 26% success rate in the control arm (n = 86). Importantly, Kaplan-Meier analysis demonstrated a survival benefit in posaconazole-treated patients. Moreover, posaconazole yielded complete or partial responses in 71% of patients with zygomycosis (N = 24). Posaconazole appears to be well tolerated over long-term administration (>1 year) and may represent an important addition to the anti-fungal armamentarium.     

Future therapies targeted towards eliminating Candida biofilms and associated infections

Introduction: Candida species are common human commensals and cause either superficial or invasive opportunistic infections. The biofilm form of candida as opposed to its suspended, planktonic form, is predominantly associated with these infections. Alternative or adjunctive therapies are urgently needed to manage Candida infections as the currently available short arsenal of antifungal drugs has been compromised due to their systemic toxicity, cross-reactivity with other drugs, and above all, by the emergence of drug-resistant Candida species due to irrational drug use.

Areas covered: Combination anti-Candida therapies, antifungal lock therapy, denture cleansers, and mouth rinses have all been proposed as alternatives for disrupting candidal biofilms on different substrates. Other suggested approaches for the management of candidiasis include the use of natural compounds, such as probiotics, plants extracts and oils, antifungal quorum sensing molecules, anti-Candida antibodies and vaccines, cytokine therapy, transfer of primed immune cells, photodynamic therapy, and nanoparticles.

Expert commentary: The sparsity of currently available antifungals and the plethora of proposed anti-candidal therapies is a distinct indication of the urgent necessity to develop efficacious therapies for candidal infections. Alternative drug delivery approaches, such as probiotics, reviewed here is likely to be a reality in clinical settings in the not too distant future.     

妊娠期外阴、阴道假丝酵母菌感染对围生结局影响的对照研究

目的 对妊娠晚期合并外阴、阴道假丝酵母菌感染(VVC)分类并探讨其对围生结局的影响.方法 对300例妊娠晚期妇女阴道分泌物进行真菌培养,筛查VVC患者,按临床特征评分分为轻度、重度VVC.随访至产后42 d,记录妊娠结局及新生儿感染情况.结果 妊娠晚期真菌感染率34%.重度VVC组在胎膜早破、胎盘胎膜粘连、早产、产时会阴延裂、产后切口裂开、新生儿感染方面明显增多,与非VVC组比较差异有统计学意义(均P＜0.01);在产褥感染方面无统计学意义(P＞0.05).结论 妊娠期重度VVC,对母婴造成不良影响,孕前、孕期应积极预防治疗.     

完带汤化裁联合西药治疗复发性外阴阴道假丝酵母菌病的Meta分析

目的 系统评价完带汤化裁联合西药治疗复发性外阴阴道假丝酵母菌病（recurrent vulvovaginal candidiasis,RVVC）的有效性和安全性。方法 检索CNKI、Sinomed、WanFang、VIP、PubMed、Embase、Cochrane Library等数据库,筛选完带汤化裁联合西药治疗RVVC的临床随机对照研究,用RevMan5.3软件进行数据分析。结果 共纳入10个研究,病例1075例。Meta分析结果显示：完带汤化裁联合西药治疗RVVC有效率高于单纯西药,且可降低复发率,改善阴道微生态,两组比较有统计学差异。结论 完带汤化裁联合西药治疗RVVC具有良好效果。     

Invasive candidiasis: future directions in non-culture based diagnosis

Introduction: Delayed initial antifungal therapy is associated with high mortality rates caused by invasive candida infections, since accurate detection of the opportunistic pathogenic yeast and its identification display a diagnostic challenge. diagnosis of candida infections relies on time-consuming methods such as blood cultures, serologic and histopathologic examination. to allow for fast detection and characterization of invasive candidiasis, there is a need to improve diagnostic tools. trends in diagnostics switch to non-culture-based methods, which allow specified diagnosis within significantly shorter periods of time in order to provide early and appropriate antifungal treatment.

Areas covered: within this review comprise novel pathogen- and host-related testing methods, e.g. multiplex-PCR analyses, T2 magnetic resonance, fungus-specific DNA microarrays, microRNA characterization or analyses of IL-17 as biomarker for early detection of invasive candidiasis.

Expert commentary: Early recognition and diagnosis of fungal infections is a key issue for improved patient management. As shown in this review, a broad range of novel molecular based tests for the detection and identification of Candida species is available. However, several assays are in-house assays and lack standardization, clinical validation as well as data on sensitivity and specificity. This underscores the need for the development of faster and more accurate diagnostic tests.     

脑血管病患者出现口腔黏膜病的调查分析

目的 调查脑血管病患者出现口腔黏膜异常的患病情况。方法 对182名脑血管病患者和166名对照进行口腔黏膜疾病的检查,比较2组间口腔黏膜疾病的患病率。结果 脑血管病患者中检出口腔黏膜病的比率要高于对照组,最常见的是口腔念珠菌病11.1%（20/182）,其次是沟纹舌5.0Study on the oral mucosal diseases in patients with cerebrovascular diseases%（9/182）、创伤性溃疡2.8%（5/182）、唇疱疹2.2%（4/182）、复发性口腔溃疡1.6%（3/182）、慢性唇炎1.6%（3/182）、白色角化症1.6%（3/182）等。结论 脑血管病患者容易出现口腔黏膜病,尤其是口腔念珠菌病,需要防范其发生和发展。     

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients

D. Neofytos, J.A. Fishman, D. Horn, E. Anaissie, C.‐H. Chang, A. Olyaei, M. Pfaller, W.J. Steinbach, K.M. Webster, K.A. Marr. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.
Transpl Infect Dis 2010: 12: 220–229. All rights reserved Abstract: Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received ≥2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12‐week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non‐lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.     

外阴阴道念珠菌感染与耐药性的分析

目的观察外阴阴道各种念珠菌的感染情况,并对常用药物的耐药性进行分析。方法收集2008年6月至2011年2月700例确诊为外阴阴道念珠菌感染患者的生殖道分泌物,采用念珠菌显色平板及SIMENS MicroScan真菌(yeast)反应板进行念珠菌菌种的分离鉴定,采用ROSCOS药片法对氟康唑、咪康唑、伊曲康唑、制霉菌素、两性霉素B进行药物耐药性及敏感性试验。结果白色念珠菌占64.57%、光滑念珠菌占14.14%、克柔念珠菌占9%、其他念珠菌占12.29%。各念珠菌对两性霉素B、制霉菌素和伊曲康唑的敏感性较高,对咪康唑、氟康唑的耐药率较高。结论女性外阴阴道念珠菌以白色念珠菌居多,对抗真菌药物有不同程度的耐药,对菌种进行鉴定和药敏实验有利于临床指导用药。