Episodes Of Candidiasis Research Articles

Blue light-emitting diode therapy for recurrent vulvovaginal candidiasis: a Brazilian report.

RVVC is defined as four or more episodes of candidiasis in a 12-month period. Conventional treatment is complex and often involves long-term medication use or multiple treatments. ABL therapy is a promising treatment option as it is acceptable to women and has only rare side effects. We conducted a prospective study with the objective of assessing the effects of antimicrobial blue light (ABL) therapy for recurrent vulvovaginal candidiasis (RVVC) in drug-resistant women. Our study enrolled RVVC drug-resistant women (defined based on clinical non-response to standard azole therapies confirmed through culture or persistence of VVC symptoms (oedema, erythema, pruritus, burning, dysuria and leucorrhea)), who received ABL through 10 sessions for 20min once a week from January 2023 to January 2024. The symptoms of Recurent VVC were assessed after 10 treatment sections and after 6 months. We included 62 patients. The overall symptoms improvement were 79% immediately after treatment and 58% after 6 months, respectively. There was an improvement in the symptoms of pruritus, burning, oedema, erythema and leucorrhoea. ABL was an effective therapy to be employed in drug-resistant women suffering from RVVC.

Brazilian organic propolis for prevention and treatment of radiation-related oral acute toxicities in head and neck cancer patients: A double-blind randomized clinical trial.

Background: Oral mucositis (OM) is one of the most important acute toxicities from radiotherapy (RT) in head and neck cancer patients and can impair oncologic treatment. Dysphagia, dysgeusia, pain, and oral candidiasis are other common toxicities. Brazilian Organic Propolis (BOP) is a recently described propolis variant and BOP types 4 and 6 have shown important antioxidant, anti-inflammatory, and antifungal properties. Purpose: To investigate the use of BOP as a preventive and/or complementary therapeutic option for radiotherapy-induced oral mucositis, dysphagia, dysgeusia, pain, and oral candidiasis. Additionally, proinflammatory cytokines were assessed to investigate their anti-inflammatory role. Methods: Sixty patients were included in this randomized, double-blind, controlled clinical trial. Patients were randomized to receive either aqueous suspension of a BOP or placebo throughout RT. Also, all patients underwent low-level laser therapy as routine oral care. OM, dysphagia, and dysgeusia were assessed weekly according to WHO and NCI scales. Pain-related to OM was assessed according to a Visual Analog Scale and the presence or absence of oral candidiasis was checked by intraoral examination. Protein levels of TNF-α and IL-1β from oral mucosa were assessed by ELISA. Results: Patients in the propolis group had a lower mean score of OM, dysphagia, dysgeusia, and most patients reported moderate pain. Fewer patients developed oral candidiasis in the propolis group, and the number of episodes was lower among patients that used BOP (p < 0.05). In addition, the BOP group presented significantly lower levels of IL-1β since the beginning of treatment when compared with placebo patients (p < 0.05) and a lower level of TNF-α at the end of treatment (p < 0.001). Conclusion: Topic use of BOP reduced TNF-α and IL-1β levels, oral candidiasis episodes, and seems to be a useful complementary option for the prevention and treatment of the main acute oral toxicities of RT. Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/rg/RBR-9f8c78/, identifier RBR-9f8c78

Efficacy and Safety of Oteseconazole in Recurrent Vulvovaginal Candidiasis

BackgroundManagement of recurrent vulvovaginal candidiasis (RVVC) is an unmet clinical challenge without approved treatment in the United States. Oteseconazole is a novel oral selective inhibitor of fungal CYP51, designed to treat RVVC without off-target toxicities. VIOLET comprised two global, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (CL-011 and CL-012). The primary objective was to evaluate oteseconazole efficacy through week 48. Key secondary objectives evaluated time to first recurrence, safety, and patient-reported outcomes.MethodsWomen with three or more symptomatic acute vulvovaginal candidiasis (VVC) episodes within the previous 12-month period, including the screening episode (in which the VVC episode cleared with fluconazole induction therapy), were randomly assigned 2:1 at baseline (maintenance phase) to 150 mg of oral oteseconazole daily for 7days and then once weekly for 11 weeks or to matching placebo for 12 weeks. Time-to-first-recurrence data were collected during the maintenance phase. Posttreatment follow-up was 36 weeks.ResultsAmong 656 women (326 in CL-011 and 330 in CL-012), the averaged percentage of participants with one or more RVVC episodes through week 48 was 6.7% (range, 6.5 to 7.4%) in CL-011 and 3.9% (3.7 to 4.6%) in CL-012 in the oteseconazole groups versus 42.8% (41.3 to 45.0%) and 39.4% (38.0 to 42.6%) in the corresponding placebo groups (P<0.001). Among oteseconazole-treated participants in CL-011 and CL-012 who experienced an RVVC episode (n=22), the mean time to recurrence was 45.7 and 47.2 weeks versus 27.8 and 33.1 weeks for placebo-treated participants (n=84), respectively (hazard ratio [95% confidence interval], 0.11 [0.06 to 0.21] for CL-011 and 0.08 [0.04 to 0.17] for CL-012; P<0.001). Types and frequencies of treatment-emergent adverse events (TEAEs) were similar between groups in both trials, with no drug-related serious TEAEs or adverse effects on pregnancy outcomes, liver function, or QT interval.ConclusionsOral oteseconazole was effective in preventing acute VVC recurrence and treating RVVC through week 48 in the CL-011 and CL-012 trials, with mostly mild TEAEs. (Funded by Mycovia Pharmaceuticals, Inc., ClinicalTrials.gov numbers, NCT03562156 for CL-011 and NCT03561701 for CL-012.)

Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections

Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.

Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis.

Vulvovaginal candidiasis is a common infection associated most often with the overgrowth of the fungal species Candida albicans. Although most women will have at least one episode of vulvovaginal candidiasis in their lifetime, some will experience recurrent infections. Recurrent vulvovaginal candidiasis can significantly impact quality of life, causing both physical and psychological symptoms, and poses a substantial financial burden for women and the health care system. Acute vulvovaginal candidiasis infections are often diagnosed symptomatically by clinicians or self-diagnosed by patients themselves; this can result in over- and underdiagnosis, as well as misdiagnosis, and has the potential to lead to ineffective treatment and incomplete infection resolution. Clinical diagnosis should include confirmatory laboratory tests, including microscopy and fungal culture, especially in women with a history of recurrent vulvovaginal candidiasis, who are more likely than women with vulvovaginal candidiasis to be infected with less-common Candida species or with azole-resistant strains. With proper diagnosis, most acute vulvovaginal candidiasis episodes can be successfully treated; however, women with recurrent vulvovaginal candidiasis may require long-term maintenance therapy. US-based guidelines recommend ⩽6 months of maintenance fluconazole treatment, but infection recurs in up to 50% of women treated. There are currently no US Food and Drug Administration–approved treatments for recurrent vulvovaginal candidiasis; however, several promising treatments for recurrent vulvovaginal candidiasis are in development.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. NCT01869829.

1173. Ocular Candidiasis in Patients with Candidemia Diagnosed by Blood Culture Versus T2Candida® Assay

BackgroundOcular candidiasis (OC) is a serious complication of candidemia. Current guidelines recommend dilated fundoscopic exam (DFE) in all patients with candidemia. In this study, we examined characteristics and outcomes of patients at UAB Medical Center with candidemia diagnosed by blood culture (BC) or T2Candida® rapid diagnostic assay (T2C) who were found to have evidence of fungal disease on ophthalmologic exam.MethodsPatients from 2016-2019 with either 1) at least one positive BC for Candida species or 2) positive T2C assay and negative or no paired BC were identified and retrospectively reviewed. Patients with additional positive BC or T2C within 60 days were excluded from the analysis. Data collected included risk factors for candidemia, causative Candida species, and whether DFE was performed after diagnosis. Patients with evidence of OC by exam were compared by type of ocular involvement (chorioretinitis vs. vitritis), whether visual symptoms were present, and whether intravitreal injection was performed.ResultsA total of 360 episodes of candidemia diagnosed by BC and 288 by T2C alone were included. Of those who underwent DFE, 33 BC patients (12.9%) had findings concerning for OC compared to 18 (8.9%) T2C patients (p=0.177) (Table 2). T2C patients with OC were younger, were more likely to have a prolonged ICU stay and to be mechanically ventilated, and were less likely to be on TPN compared to the BC group. Identification of C. parapsilosis was significantly more common in T2C patients (Table 1). There were no significant differences in presence of visual symptoms, type of ocular involvement, need for intravitreal injection, or 30-day mortality (Table 3).Table 1. Demographics and risk factors Table 2. Episodes of candidemia and ocular candidiasis by year Table 3. Ocular findings and outcomes ConclusionThe frequency of ocular disease was similar between groups. Significantly more T2C patients had candidemia due to C. parapsilosis, and the groups differed in terms of risk factors for candidemia. There were no differences in frequency of intravitreal injection, severity of eye disease, or mortality. Despite recent concerns about the necessity of DFE in asymptomatic patients with candidemia, we believe these results emphasize the importance of performing DFE in candidemic patients and also support the practice of doing so in patients with positive T2C even in the absence of positive blood cultures.Disclosures Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator)

Ocotea glomerata (Nees) Mez Extract and Fractions: Chemical Characterization, Anti-Candida Activity and Related Mechanism of Action.

Background: Opportunistic fungal infections are increasingly common, with Candida albicans being the most common etiological agent; however, in recent years, episodes of candidiasis caused by non-albicans Candida species have emerged. Plants belonging to the Lauraceae family have shown remarkable antifungal effects. This study assessed the anti-Candida activity of Ocotea glomerata extracts and fractions, time of death and the synergistic effects with conventional antifungals. The possible mechanism of action was also addressed. Methods: Minimal inhibitory concentrations (MIC) were determined by broth microdilution technique, and the mechanism of action was assessed by ergosterol, sorbitol, cell viability, reactive oxygen species (ROS) generation and phosphatidylserine externalization tests. Results: All the tested extracts evidenced antifungal activity, but the methanol extract was revealed to be the most effective (MIC = 3.12 μg/mL) on C. krusei. The combination of methanol extract with ketoconazole and fluconazole revealed a synergistic effect for C. krusei and C. albicans, respectively. Fractions 1 and 5 obtained from the methanol extract had fungicidal activity, mainly against C. krusei. Methanol extract did not reveal effects by ergosterol and sorbitol assays; however, it led to an increase in intracellular ROS levels, decreased cell viability, and consequently, cell death. Conclusion: O. glomerata methanol extract may be viewed as a rich source of biomolecules with antifungal activity against Candida spp.

Influence of recurrent vulvovaginal candidiasis on quality of life issues.

More than 370 million women will experience recurrent vulvovaginal candidiasis (RVVC) during their lifetime. However, RVVC is often trivialized as clinically insignificant and not worthy of research funding. We evaluated the influence of RVVC on the quality of life in affected women. The validated World Health Organization Quality of Life Abbreviated Assessment (WHOQOL-Bref) questionnaire was administered to 100 women with RVVC and to 101 epidemiologically matched women with no history of vulvovaginal candidiasis. RVVC was defined as at least four episodes of clinical and culture-positive vaginal candidiasis within a 1year period. Data were analyzed by Chi square, Student t test and analysis of variance. Internal consistency of responses to questions was evaluated by Cronbach alpha. The Cronbach alpha coefficient was > 0.80 for responses to generalized questions and > 0.65 for answers to more specific questions, indicating substantial internal consistency. Perception of quality of life and satisfaction with their health was greatly reduced in the RVVC group (p < 0.001). Diminished responses to physical and psychological well-being were also reported by women with RVVC (p < 0.001). Various aspects of social relations including sexual activity were similarly reduced (p < 0.001) as were satisfaction with issues such as home environment, financial resources and employment (p < 0.001). RVVC affects multiple aspects of a woman's well-being. Women with this condition deserve serious attention from clinicians and research into susceptibility, prevention and treatment of this infection deserves much greater emphasis.

Treatment of oropharyngeal candidiasis in immunocompetent and immunocompromised patients

Treatment of oropharyngeal candidiasis in immunocompetent and immunocompromised patients

Long-Term Outcomes of Women With Recurrent Vulvovaginal Candidiasis After a Course of Maintenance Antifungal Therapy.

Data about long-term clinical outcome after a course of maintenance fluconazole in those with recurrent vulvovaginal candidiasis (RVVC) is lacking. We aimed to determine the rate of recurrence at a minimum of 6 months after completion of maintenance therapy. A retrospective analysis of women with Candida albicans RVVC from January 2008 to January 2017 was performed using chart review to obtain information about recurrence after maintenance therapy. Patients were considered resolved if they had no further episodes of candidiasis, sporadic with less than 3 episodes yearly and ongoing with greater than 3 episodes yearly. Approximately 1,672 patients with C. albicans vaginal isolates were identified. Of these, 201 met the criteria for RVVC. The mean age was 40.4 years; 151 (77.4%) were white, 133 (66.2%) had comorbid vulvar conditions, and 76 (37.8%) had a risk factor for vulvovaginal candidiasis. One hundred twenty complete charts were further analyzed. The mean length of follow-up after discontinuing maintenance therapy was 39.9 months. After the initial course, 23 (19.2%), 21 (17.5%), and 76 (63.3%) were resolved, sporadic and ongoing, respectively. Risk factors, comorbid vulvar conditions, obesity, menopause status, and length of therapy were not associated with relapse. Age 40 or older was associated with relapse (p = .018). Of the 201 total patients with RVVC, 22 (10.9%) of patients self-reported at least 1 adverse event. The most common was gastrointestinal symptoms (8 [4%]). Although RVVC can be controlled, relapse is common after an initial course of maintenance fluconazole. Ongoing maintenance remains the most effective treatment option.

Mutation in the C receptor of Interleukin 17, as a cause of Chronic Mucocutaneous Candidiasis

Background: The humoral and cellular immunity plays a preponderant role in the etiopathogenesis of esophagitis, for which the majority of the patients who present this pathology will have some type of immune system. Methods & Materials: Patient of 36 years of age, family history of Hiper IgE syndrome, consulted for abdominal pain, enterorrhagia, weight loss, dysphagia and vomiting. The physical examination shows important muguet. Regarding to personal history, it is recognized that thepatients episodes of candidiasis esophagitis from the age of 6 years and cutaneous plasmocytoma located in the wing of the nose that required surgical extirpation. Results: In endoscopic exploration, the esophagus appears hyperemic, with yellowish mucous plaques that adhere firmly, with rough and friable underlying surface after removal. Pathological anatomy informs esophagitis, with presence of yeasts compatible with Candida on the mucosal surface. In the stomach, the lamina propria presents edema with lymphocyte hypercellularity. Microbiology: Candida albicans. The patients begins treatment with Fluconazole. Laboratory: HIV negative Elisa, non-reactive HBsAg, non-reactive HCV antibodies. IgG 1727 mg/dl, IgA 271 mg/dl, IgM 154 mg/dl, IgE 172 mg/dl. CD3 2123 (76.8%), CD4 1024 (46.6%), CD8 674 (24.4%), CD19 498 (15.8%). A molecular biology study was carried out in search of mutations in the AIRE gene, sequencing of exons and adjacent intronic sequences, showing no alterations compatible with mutation. The mutation of this gene is linked to several autoimmune diseases, such as hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidiasis. In a new molecular study, it shows mutation in the C IL 17 receptor (IL17RC). This interleukin is related in the antifungal defense. Conclusion: Interleukin 17 participates in the development of autoimmunity, inflammation and tumor immunity, playing an important role in the defense against bacterial and fungal infections. The blocking of IL-17 signaling due to the mutation of its receptor prevents the formation of germinal centers and reduces the humoral response. The discovery of this mutation is a rarity, and plays an important role in defense against infectious diseases. In this clinical case, this mutation predisposes to the recurrence of chronic mucocutaneous candidiasis.

Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates

BackgroundInvasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups.MethodsEpisodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed.ResultsA total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64–33.56; P < 0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80–17.41; P < 0.001), renal failure (OR 5.38; 95% CI 1.99–14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04–8.67; P = 0.043).ConclusionsNeonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.

A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of orally administered VT-1161 in the treatment of recurrent vulvovaginal candidiasis

Lanosterol demethylase is an enzyme that is essential for fungal growth and catalyzes an early step in the biosynthetic pathway of ergosterol, which is a sterol that is required for fungal cell membrane formation and integrity. Lanosterol demethylase is the molecular target of the class of drugs referred to as "azole antifungals." VT-1161 is a novel, oral, selective inhibitor of fungal lanosterol demethylase and is being developed for the treatment of recurrent vulvovaginal candidiasis. We evaluated the efficacy and safety of 4 dosing regimens of oral VT-1161 compared with placebo in women with recurrent vulvovaginal candidiasis, which was defined as at least 3 symptomatic episodes of acute vulvovaginal candidiasis within a 12-month period. Two hundred fifteen women with a documented history of recurrent vulvovaginal candidiasis and who, at screening, were experiencing an episode of acute vulvovaginal candidiasis (acute vulvovaginal candidiasis; composite vulvovaginal signs and symptoms score of ≥3 and a positive potassium hydroxide test for yeast) were enrolled. After treatment of the acute infection with fluconazole, subjects were assigned randomly to 1 of 5 treatment regimens: (1) VT-1161 150 mg once daily for 7 days, then 150 mg once weekly for 11 weeks, followed by a once-weekly dose of placebo for 12 weeks; (2) VT-1161 300 mg once daily for 7 days, then 300 mg once weekly for 11 weeks, followed by a once-weekly dose of placebo for 12 weeks; (3) VT-1161 150 mg once daily for 7 days, then 150 mg once weekly for 23 weeks; (4) VT-1161 300 mg once daily for 7 days, then 300 mg once weekly for 23 weeks; or (5) a matching placebo regimen for 24 weeks. The primary efficacy outcome was the proportion of subjects with ≥1 culture-verified acute vulvovaginal candidiasis episodes through week48. In the intent-to-treat population, the proportion of subjects with ≥1 acute vulvovaginal candidiasis episodes ranged from 0-7% across the 4 VT-1161 arms vs 52% in the placebo arm, with all arms achieving statistical significance vs placebo. VT-1161 was well-tolerated with a favorable safety profile, and the incidence of adverse events was lower in all VT-1161 arms compared with placebo. In addition, no patient in any VT-1161 arm discontinued the study early because of an adverse event or laboratory abnormality. There was also no evidence of an adverse effect of VT-1161 on liver function or electrocardiogram recordings. In this study, VT-1161 was shown to be efficacious and safe in the treatment of patients with recurrent vulvovaginal candidiasis. These data strongly support further clinical investigation of VT-1161 for the treatment of recurrent vulvovaginal candidiasis.

The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid.

Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect in vitro with the absence of glucose in medium of culture, which underlines the complex interactions that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs, and the role of MIG1, we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) MIG1 regulation of C. albicans, and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in C. albicans involving membrane transporters, which could be exploited to control yeast colonization in human body niches.

Recurrent episodes of esophageal candidiasis without dysphagia post-Guillain-Barré syndrome: an unusual presentation of achalasia

Here, we present a case of a 50-year-old male with a history of a Guillain-Barré-syndrome, who was referred to our clinic with recurrent esophageal candidiasis and long-standing intermittent retrosternal cramps...

Microbial epidemiology of candidaemia in neonatal and paediatric intensive care units at the Children's Medical Center, Tehran.

Invasive candidiasis is a major cause of morbidity and mortality in children. However, limited data are available on the epidemiology of this infection in paediatric settings in Iran. The aim of this study was to determine the prevalence, microbial epidemiology, risk factors and clinical outcomes associated with candidaemia in intensive care units at the Children's Medical Center, Tehran, Iran. All blood and other normally sterile specimen cultures positive for Candida species were included. Isolates were identified by morphological and molecular methods. Unidentified/doubtful yeast isolates were subjected to ITS sequencing. A total of 156 episodes of invasive candidiasis, with an overall incidence of 15.2 per 1000 ICU admissions, was recorded. Risk factors included presence of central venous lines (89.1%), mechanical ventilation (55.8%) and parenteral nutrition (51.3%). Candida albicans (57.1%) and Candida parapsilosis (24.4%) were the most commonly isolated species. Candida orthopsilosis, Candida glabrata, Candida dubliniensis, Candida lusitaniae, Candida kefyr and Candida intermedia accounted for about 11% of the cases. The overall mortality rate was 42.5%. Non-albicans Candida species accounted for nearly half of the cases of paediatric candidaemia. This is the first prospective study of candidaemia in paediatric settings in Iran and serves to inform necessary interventions for the prevention of candidaemia.

Oropharyngeal candidiasis among HIV seropositive patients in Chennai, South India: An evaluation of Polymerase chain reaction-Restriction Fragment Length polymorphism for speciation and Antifungal drug resistance

CONTEXT: Oropharyngeal candidiasis is a common opportunistic manifestation of HIV/acquired immunodeficiency syndrome. Non-albicans Candida and drug-resistant strains are on the rise leading to treatment difficulties. AIMS: The present study aims to speciate, perform antifungal susceptibility, and also to evaluate the significance of antifungal drug resistance by correlating the prior exposure to Fluconazole and CD-4 counts. SETTINGS AND DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: A total of 115 HIV patients with clinical evidence of oropharyngeal candidiasis were included in the study. Two swabs were collected from the lesions. Speciation and antifungal susceptibility by microbroth dilution method for fluconazole, itraconazole, and amphotericin B were done as per the standard microbiological techniques. Polymerase chain reaction and restriction fragment length polymorphism (PCR and RFLP) were performed for speciating the Non-albicans candida. The association between prior exposure to Fluconazole, CD-4 counts, and antifungal resistance was assessed (Fisher's exact test, Chi-square test P RESULTS: Among the 115 patients, 60 (52.17%) showed culture positivity for Candida species. Candida albicans 35 (56.45%) was the predominant species isolated followed by Candida tropicalis 12 (19.30%). PCR RFLP produced specific products for 19 of the non albicans Candida. A resistance of 17 (27.41%) and 18 (29.00%) was seen to fluconazole and itraconazole, respectively. A significant association was observed between prior exposure to Fluconazole and drug resistance (P = 0.0201).The correlation between CD-4 counts and antifungal resistance was not statistically significant (P = 0.595). CONCLUSION: Antifungal susceptibility testing should be performed routinely along with species-level identification whether it is the first or recurrent episode of oral candidiasis and therapy should be modified accordingly to prevent the morbidity and mortality.

Prevalence Rate of Vulvovaginal Candidiasis and Identification of Candida Species in Women in Referred to Hamedan Hospitals 2013 - 2014, West of Iran

Background: Vulvovaginal candidiasis is a common gynecological finding among the women worldwide. Objectives: In this study determine of prevalence rate of vulvovaginal candidiasis and identification of Candida species was investigated. Patients and Methods: In this cross-sectional study study, 350 females selected and examined by wet mount and culture procedure. Results: The prevalence rate, by means of culture procedure was 26%. Candida albicans was responsible for 81.3% episodes of volvovaginal candidiasis. Conclusions: In order to decrease the prevalence rate of vulvovaginitis, more epidemiological surveillance and accurate informative programs about public health care, symptoms and signs and transmission ways should be performed in the future.

AVALIAÇÃO DA ATIVIDADE ANTIFÚNGICA DE Curcuma longa SOBRE Candida parapsilosis

Among fungal infections that affect human beings, candidiasis has significant relevance. Its most common etiological agent is Candida albicans, but over the past three decades candidiasis episodes caused by other species, such as Candida parapsilosis, have emerged. The Brazilian Cerrado has a huge morphological diversity of plants. Curcuma longa, a plant widely found in this biome, has been studied both for its antibacterial and antifungal activity. The aim of this study was to evaluate the antifungal activity of C. longa on C. parapsilosis by analyzing the inhibitory capacity of extracts from different parts of the plant on the fungus. The antifungal activity of ethanolic extracts from rhizomes and leaves of C. longa was evaluated by the macrodilution method, determining the minimum inhibitory concentration (MIC), alongside sensitivity testing performed in plates and by the diffusion disk method. We also evaluated the synergy between the extracts in combination with traditional antifungal drugs. C. longa has antifungal activity on the growth of C. parapsilosis with a MIC value obtained from ethanolic extracts of 500 ppm for rhizomes and leaves. It was possible to observe synergistic activity between the leaf extracts and amphotericin B and antagonistic activity between rhizome extracts and amphotericin B. It may be concluded that the leaf and rhizome extracts of C. longa have antifungal activity against C. parapsilosis in a dose-dependent manner, showing the antifungal potential of the plant