Cellular apoptosis and necrosis as therapeutic targets for novel Eugenol Tosylate Congeners against Candida albicans.

Despite the rise of new Candida species, Candida albicans tops the list with high morbidity and mortality rates. To tackle this problem there is a need to explore new antifungals that could replace or augment the current treatment options. We previously reported that tosylation of eugenol on hydroxyl group resulted in molecules with enhanced antifungal potency. In line with that work, we synthesized new eugenol tosylate congeners (ETC-1-ETC-7) with different substituents on pendent sulfonyl group and tested their susceptibility against different fluconazole susceptible and resistant C. albicans strains. We evaluated physiology and mode of cell death in response to the most active derivatives by analyzing major apoptotic markers in yeast such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization and decrease in cytochrome c oxidase activity. The results demonstrated that all C. albicans strains were variably susceptible to the test compounds with MIC ranging from 0.125-512 µg/ml, and the most active compounds (ETC-5, ETC-6 and ETC-7) actuate apoptosis and necrosis in Candida cells in a dose-dependent manner via metacaspase-dependent pathway. Furthermore haemolytic assay showed low cytotoxicity effect of these ETCs. Overall the results indicated that ETCs exhibit potential antifungal activity against C. albicans by activating apoptotic and necrotic pathways.

Mrr2 mutations and upregulation are associated with increased fluconazole resistance in Candida albicans isolates from patients with vulvovaginal candidiasis.

Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). The aim of this study was to evaluate Mrr2 mutation and its expression levels and Candida drug resistance 1 (Cdr1) in C. albicans associated with fluconazole (FCA) resistance. We identified 80 isolates of C. albicans from 155 vaginal secretions and performed FCA drug sensitivity tests, using M27-A3 micro-broth dilution. We extracted DNA, sequenced Mrr2, and performed reverse transcriptase-quantitative PCR polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of Mrr2 and Cdr1. In total, 40 isolates were sensitive, 10 were dose-dependently sensitive, and 30 were resistant to FCA. Mrr2 mutation occurred in 56·67% isolates, which was significantly higher than that in the FCA sensitive group (26·08%, P < 0·05). The mRNA expression level of Cdr1 in the FCA resistant group was significantly higher than that in the sensitive group Cdr1 (0·42 ± 0·294 vs 0·25 ± 0·289, P < 0·05). The odds ratio of FCA-resistant occurrence in C. albicans with Mrr2 mutation and high expression levels was 47·5 times higher than C. albicans without Mrr2 mutation and low expression levels. The results may provide new insights for improving VVC treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). Fluconazole (FCA) is the most widely used drug in VVC infection. However, the widespread use of FCA has severely increased the incidence of FCA-resistant fungus. Therefore, the mechanism underlying FCA resistance in C. albicans must be elucidated urgently. This study demonstrated that high expression of Cdr1 and Mrr2 may directly be linked to C. albicans resistance to FCA, and high expression of Mrr2 may promote high expression of Cdr1 and mediate resistance of C. albicans to FCA. The results may provide new insights for improving VVC treatment.

Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy.

Rezafungin acetate is a novel echinocandin in clinical development for prevention and treatment of invasive fungal infections. Rezafungin is differentiated by a pharmacokinetic/pharmacodynamic (PK/PD) profile that includes a long half-life allowing once-weekly administration, front-loaded plasma drug exposures associated with antifungal efficacy, and penetration into deep-seated infections, such as intra-abdominal abscesses. In this series of in vivo studies, rezafungin demonstrated efficacy in the treatment of neutropenic mouse models of disseminated candidiasis, including infection caused by azole-resistant Candida albicans, and aspergillosis. These results contribute to a growing body of evidence demonstrating the antifungal efficacy and potential utility of rezafungin in the treatment of invasive fungal infections.

Selective and Sensitive Probe Based in Oligonucleotide-Capped Nanoporous Alumina for the Rapid Screening of Infection Produced by Candida albicans.

A robust, sensitive, and time-competitive system to detect Candida albicans in less than 30 min in clinical samples based in capped nanoporous anodic alumina (NAA) is developed. In the proposed design, NAA pores are loaded with rhodamine B and then blocked with an oligonucleotide that is able to recognize C. albicans DNA. The capped material shows negligible cargo release, whereas dye delivery is selectively accomplished when genomic DNA from C. albicans is present. This procedure has been successfully applied to detect C. albicans in clinical samples from patients infected with this yeast. When compared with classical C. albicans detection methods, the proposed probe has a short assay time, high sensitivity and selectivity, demonstrating the high potential of this simple design for the diagnosis of infection produced by C. albicans.

Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia.

Candida albicans is the most frequently isolated fungal species in hospital settings worldwide. However, non-albicans Candida species with decreased susceptibility to antifungals have emerged as an important cause of fungemia. The aims of this study were to determine the species distribution of fungi isolated from the blood samples of patients at a Swedish University Hospital and to define the in vitro susceptibilities of these isolates to nine antifungal agents. In total, 233 yeast isolates from 143 patients were included in this study. Antifungal susceptibility testing was performed using broth dilution Sensititre YeastOne panels, which comprised amphotericin B, 5-flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, and caspofungin. The most common species in all age groups was C. albicans (n = 93, 65%), followed by C. glabrata (n = 27, 19%) and C. parapsilosis (n = 15, 10%). C. glabrata was mostly found in elderly individuals, while C. parapsilosis was found mainly in young children (p = 0.008). Antifungal resistance was low in the Candida species, except for reduced susceptibility to fluconazole among C. glabrata strains. C. albicans is the most frequent colonizer of Swedish patients. In general antifungal resistance is uncommon in Candida species. Nevertheless, reduced susceptibilities to fluconazole and echinocandins were found in C. glabrata and C. parapsilosis, respectively.

Molecular mechanisms of azole resistance in Candida bloodstream isolates.

BACKGROUND: Antifungal resistance rates are increasing. We investigated the mechanisms of azole resistance of Candida spp. bloodstream isolates obtained from a surveillance study conducted between 2012 and 2015. METHODS: Twenty-six azole non-susceptible Candida spp. clinical isolates were investigated. Antifungal susceptibilities were determined using the Sensititre YeastOne® YO10 panel. The ERG11 gene was amplified and sequenced to identify amino acid polymorphisms, while real-time PCR was utilised to investigate the expression levels of ERG11, CDR1, CDR2 and MDR1. RESULTS: Azole cross-resistance was detected in all except two isolates. Amino acid substitutions (A114S, Y257H, E266D, and V488I) were observed in all four C. albicans tested. Of the 17 C. tropicalis isolates, eight (47%) had ERG11 substitutions, of which concurrent observation of Y132F and S154F was the most common. A novel substitution (I166S) was detected in two of the five C. glabrata isolates. Expression levels of the various genes differed between the species but CDR1 and CDR2 overexpression appeared to be more prominent in C. glabrata. CONCLUSIONS: There was interplay of various different mechanisms, including mechanisms which were not studied here, responsible for azole resistance in Candida spp in our study.

[Antimycotic therapy impact on oral mucosa Candida species composition in HIV-infected patients]. / Vliianie antimikoticheskoi terapii na vidovoi i shtammovyi sostav gribov roda Candida polosti rta bol'nykh VICh-infektsiei.

RESEARCH OBJECTIVES: the analysis of a specific and strains drift of Candida in HIV/AIDS patients with oropharyngeal candidiasis and the analysis of Candida sensitivity dynamics to reference antimycotic drugs. The study comprised 49 HIV-infected patients aged 20-69 years. The study revealed candidiasis treatment provides specific and strains drift of Candida. Eradication of fluconazole sensitive C. albicans leads to growth of more resistant strains (C. glabratae, krusei, tropicalis) thus lowering antimycotic therapy efficacy. The efficacy improvement requires selective approach to candidiasis treatment with azol agents.

Correlation between antifungal consumption and the distribution of Candida species in different hospital departments of a Lebanese medical Centre.

BACKGROUND: In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have described the distribution of Candida species among different hospital departments and calculated the antifungal consumption in our facility. We also correlated the consumption of certain antifungals and the prevalence of specific Candida species. METHODS: This was a retrospective review of all the Candida isolates recovered from the computerised microbiology laboratory database of Makassed General Hospital, a tertiary care centre in Beirut, Lebanon, between January 2010 and December 2015. Data on antifungal consumption between January 2008 and December 2015 were extracted from the hospital pharmacy electronic database. We used Spearman's coefficient to find a correlation between Candida species distribution and antifungal consumption. RESULTS: Between 2008 and 2015, we observed that the highest antifungal consumption was in the haematology/oncology department (days of therapy/1000 patient days = 348.12 ± 85.41), and the lowest was in the obstetrics/gynaecology department (1.36 ± 0.47). In general, the difference in antifungal consumption among various departments was statistically significant (P < 0.0001). Overall, azoles were the most common first-line antifungals in our hospital. Echinocandins and amphotericin B were mostly prescribed in the haematology/oncology department. As for Candida species distribution, a total of 1377 non-duplicate isolates were identified between 2010 and 2015. A non-homologous distribution of albicans vs. non-albicans was noted among the different departments (P = 0.02). The most commonly isolated NAC was Candida glabrata, representing 14% of total Candida species and 59% of NAC. Candida famata (9% of NAC), Candida parapsilosis (3.6% of NAC) and Candida krusei (3% of NAC) were recovered unequally from the different departments. The total antifungal consumption correlated positively with the emergence of NAC. The use of azoles correlated positively with Candida glabrata, while amphotericin B formulations correlated negatively with it. None of these correlations reached statistical significance. CONCLUSION: Different Candida species were unequally distributed among different hospital departments, and this correlated with consumption of antifungals in respective departments, highlighting the need for antifungal stewardship.

Treatment of Renal Fungal Ball with Fluconazole Instillation Through a Nephrostomy Tube: Case Report and Literature Review.

BACKGROUND Urinary tract candida infection can be due either to hematogenous dissemination of the organism or a retrograde infection. In debilitated or immunosuppressed septic patients, who have upper urinary tract obstruction with renal filling defect, fungal infection should be considered. We report on a patient with sepsis and renal fungal ball who was treated with percutaneous nephrostomy and intravenous antifungal agent, but the patient did not respond so instillation of fluconazole through nephrostomy was given. CASE REPORT A 60-year-old male patient with a known case of diabetes mellitus with refractory urine retention underwent transurethral resection of the prostate. Postoperatively, the patient developed recurrent high-grade fever with left loin pain, and elevated septic parameters; urine and blood culture were positive for Candida albicans. Computed tomography urography showed left hydronephrosis with filling defect in the left renal pelvis with suspected renal fungal ball. Left percutaneous nephrostomy was performed and intravenous fluconazole started but the fever did not subside, therefore, the treatment was changed to anidulafungin. The patient improved but urine from both the bladder and the nephrostomy remained positive for candida. Instillation of fluconazole at 300 mg in 500 mL normal saline was applied through the nephrostomy tube over 12 hours at 40 mL/hour for 7 days. CONCLUSIONS Renal fungal ball is rare but can be serious, especially in immunocompromised patients. Management options for renal fungal ball include intravenous antifungal agents and percutaneous nephrostomy with antifungal instillation of antifungal agents. The objective of this case report was to document treatment success with the use of fluconazole instillation through a nephrostomy tube.

Natural Products for Vulvovaginal Candidiasis Treatment: Evidence from Clinical Trials.

BACKGROUND: Candida albicans is an opportunistic yeast that causes more than 90% of all vulvovaginal infections. Because of being inherently resistant to antifungals drugs such as azole derivatives, the search for anti-Candida albicans agents with new pharmacological targets is considered as the main therapeutic strategy to prevent and treat these types of infections. In this context, products of natural origin are a promising source of compounds with antifungal activity. OBJECTIVE: The current review analyzes clinical evidence on the effectiveness of natural products in the vulvovaginal Candida albicans infections. METHOD: A literature review in the electronic databases PubMed, Google Scholar, Cochrane Library Plus, Web of Science, Latin American and Caribbean Literature on Health Sciences (Lilacs) and Scientific Electronic Library Online (SciELO) using the search terms "Natural Products", "Phytotherapy", "Vulvovaginal Candidiasis" and "Clinical Trials" together with the Boolean term 'AND' was performed. English, Spanish and French articles without restriction of date of publication were considered. RESULTS: A total of 13 clinical trials (most of them randomized clinical trials which used azoles as control group) evaluated the anti-Candida activity of a total of 11 different natural products (i.e. Zataria multiflora essential oils, Ageratina pichinchensis and Solanum nigrescens extracts and saponins from Solanum chrysotrichum, among others) against vulvovaginitis have been included in the current review. CONCLUSION: Because of the few clinical trials it is difficult to establish a consistent conclusion about the effectiveness of natural products in the prevention and treatment of vulvovaginitis caused by Candida albicans. Future studies should be aimed at evaluating new natural products as well as conducting more clinical research with promising natural substances already investigated in clinical trials.

Comparison of the recovery rate of otomycosis using betadine and clotrimazole topical treatment / Comparação da taxa de recuperação de otomicose com o uso de tratamento tópico com betadina e clotrimazol

Abstract Introduction Otomycosis is a common diseases that can be associated with many complications including involvement of the inner ear and mortality in rare cases. Management of otomycosis can be challenging, and requires a close follow-up. Treatment options for otomycosis include local debridement, local and systemic antifungal agents and utilization of topical antiseptics. Objective This study was designed to compare the recovery rate of otomycosis using two therapeutic methods; topical betadine (Povidone-iodine) and clotrimazole. Methods In this single-blind clinical trial, 204 patients with otomycosis were selected using a non-probability convenient sampling method and were randomly assigned to two treatment groups of topical betadine and clotrimazole (102 patients in each group). Response to treatment was assessed at 4, 10 and 20 days after treatment. Data were analyzed using the independent t-test, Chi-Square and Fisher exact test in SPSS v.18 software, at a significance level of p < 0.05. Results The results showed that out of 204 patients with otomycosis, fungi type isolated included Aspergillus in 151 cases (74%), and Candida albicans in 53 patients (26%). On the fourth day after treatment, 13 patients (13.1%) in the group treated with betadine and 10 patients (9.8%) in the group treated with clotrimazole showed a good clinical response to treatment (p = 0.75). A good response to treatment was reported for 44 (43.1%) and 47 patients (46.1%) on the tenth day after the treatment (p = 0.85); and 70 (68.6%) and 68 patients (67.6%) on the twentieth day after treatment (p = 0.46) in the groups treated with betadine and clotrimazole, respectively. The response to treatment was thus not significantly different in the two groups. Conclusion In the present study the efficacy of betadine and clotrimazole was the same for the treatment of otomycosis. The result of this study supports the use of betadine as an effective antifungal in otomycosis treatment, helping to avoid the emergence of resistant organisms.

Resumo Introdução A otomicose é uma das doenças comuns associadas a muitas complicações, como envolvimento da orelha interna e mortalidade em casos raros. O tratamento da otomicose pode ser realmente desafiador e requer um acompanhamento rigoroso. As opções de tratamento para otomicose podem incluir desbridamento local, agentes antifúngicos locais e sistêmicos e uso de antissépticos tópicos, os medicamentos tópicos recomendados para o tratamento da otomicose. Objetivo Comparar a taxa de recuperação de otomicose utilizando dois métodos terapêuticos de betadina tópica (povidona-iodo) e clotrimazol. Método Neste ensaio clínico simples cego, 204 pacientes com otomicose foram selecionados utilizando-se método de amostragem de não probabilidade conveniente e randomizados para dois grupos de tratamento, com betadina tópica e com clotrimazol (102 pacientes em cada grupo). A resposta ao tratamento foi avaliada aos 4, 10 e 20 dias após o tratamento. Os dados foram analisados utilizando o teste t independente, qui-quadrado e teste de Fisher no software SPSS v.18, com nível de significância de p < 0,05. Resultados Os resultados mostraram que dos 204 pacientes com otomicose, os tipos de fungos isolados incluíram Aspergillus em 151 casos (74%) e Candida albicans em 53 pacientes (26%). No quarto dia após o tratamento, 13 pacientes (13,1%) no grupo tratado com betadina e 10 pacientes (9,8%) no grupo tratado com clotrimazol apresentaram boa resposta ao tratamento (p = 0,75). Uma boa resposta ao tratamento foi relatada para 44 (43,1%) e 47 pacientes (46,1%) no décimo dia após o tratamento (p = 0,85); e 70 (68,6%) e 68 pacientes (67,6%) no vigésimo dia após o tratamento (p = 0,46) no grupo tratado com betadina e clotrimazol, respectivamente. Assim, a resposta ao tratamento não foi significativamente diferente nos dois grupos. Conclusão No presente estudo, a eficácia da betadina e do clotrimazol foi a mesma no tratamento da otomicose. O resultado deste estudo apoia o uso de betadina como um antifúngico eficaz no tratamento da otomicose que pode ajudar a evitar o surgimento de organismos resistentes.

Iranian HIV/AIDS patients with oropharyngeal candidiasis: identification, prevalence and antifungal susceptibility of Candida species.

Oropharyngeal candidiasis is the commonest mucocutaneous infection in HIV-positive individuals. Herein, samples were taken from oral cavities of 150 HIV-infected patients and cultured on Sabouraud-dextrose agar; 89 (59·3%) of 150 patients had positive culture for Candida and presented clinical sign of classical oral candidiasis. Totally, 102 morphologically distinct colonies were isolated from Candida positive cultures and subsequently identified by polymerase chain reaction and sequencing assay, presenting the following frequency: 54 C. albicans (52·9%), 16 C. dubliniensis (15·7%), 12 C. tropicalis (11·8%), 9 C. glabrata (8·8%), 7 C. kefyr (6·9%) and 4 C. africana (3·9%). Additionally, multiple Candida species were co-isolated from 13·5% (12/89) patients. Regarding the antifungal susceptibility test, which was performed by CLSI protocol (M27-A3/M27-S3), all Candida isolates were susceptible to amphotericin B and caspofungin, while some of them were resistant to fluconazole (17·6%; 16 C. albicans, 1 C. dubliniensis and 1 C. glabrata), itraconazole (16·7%; 15 C. albicans, 1 C. dubliniensis and 1 C. tropicalis) and voriconazole (5·9%; 5 C. albicans and 1 C. tropicalis). Collectively, our findings reinforce the urgent necessity to find new therapeutic agents to treat oral candidiasis in HIV-positive patients, especially due to the high incidence of azole-resistant Candida strains and the increased frequency of non-C. albicans species. SIGNIFICANCE AND IMPACT OF THE STUDY: The Candida species recovered from oral cavity of 150 Iranian HIV/AIDS patients and their antifungal susceptibility profiles were reported. Candida albicans was the commonest Candida species, followed by C. dubliniensis, C. tropicalis, C. glabrata, C. kefyr and C. africana. All Candida isolates were susceptible to amphotericin B and caspofungin, while resistance to azoles was detected. The growing drug-resistance profile reported in clinical isolates of C. albicans and non-C. albicans strains is a serious problem in hospitals worldwide. Consequently, the suitable antifungal choice to treat the HIV/AIDS population with oral candidiasis needs to be rethought and new therapeutic options must urgently arise.

Role of chemical and herbal dentifrices against indigenous oral Pathogens.

The oral cavity has its own significant micro-flora but under unhygienic conditions can cause infections or diseases like gingivitis, caries, plaque and gum bleeding. Out of more than 700 oral microbial species, some opportunistic pathogens such as Staphylococcus aureus, Streptococcus spp. and Candida albicans are more prevalent. In this study, the antimicrobial activities of various toothpastes (dilutions ranging from 1:1-1:128) against above mentioned pathogens were assessed. The pathogens were isolated from clinical samples using various differential and selective media and identified through microscopic examination, cultural characteristics and biochemical tests using both conventional and API kit system (Biomerieux, France). Antimicrobial activities of selected dentifrice formulations against identified microbes were determined using agar well diffusion and Minimum Inhibitory Concentration assays. Statistical analysis of the data on different variables has been performed by Analysis of Variance and Mean ±SD using SPSS software. From the collected samples Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius, Streptococcus intermedius and Candida albicans were isolated and identified. All the selected toothpastes showed significant (p<0.01) antimicrobial activity against the bacterial and fungal isolates. Variable results (inhibitory zone diameters ranging from 35.10±8.00 to 2.40±5.37) were found when mean of different dilutions were compared. Conventional dentifrices exhibited more inhibition as compared to herbal products.

Oral Candida colonization and plaque type psoriasis: Is there any relationship?

AIM: The potential role of superantigens derived from microbial agents could be considered in the pathogenesis of psoriasis, but the association between Candida albicans and psoriasis severity is still controversial. The present study was designed to compare the prevalence of oral candidiasis in a group of psoriatic patients and healthy patients, and its correlation with psoriasis severity. METHODS: Seventy psoriatic patients with no history of systemic treatment and 70 closely-matched control patients underwent oral examination. Scraping of oral mucosa to detect Candida species was done using a sterile cytobrush. RESULTS: Candida was detected in the oral cavity of 20% of patients with psoriasis and 2.8% of control cases (P = .002), but none had clinical features of oral candidiasis. Candida albicans was the only species isolated from the oral cavity of both groups. No correlation was found between sex, age, phototherapy, and presence of oral candidiasis. There was a positive correlation between psoriasis severity and colony count (P < .001). CONCLUSIONS: The prevalence of oral candidiasis is higher in psoriatic patients and is associated with disease severity. It is not exactly clear whether oral candidiasis can aggravate psoriasis or if psoriasis can predispose patients to oral candidiasis.

Estudio clínico y micológico de otomicosis en diabéticos: una serie de 17 casos / Clinical and mycological study of otomycosis in diabetics: series of 17 cases

RESUMEN Introducción: La otomicosis en pacientes inmunosuprimidos esta caracterizada por ser bilateral y ser causada por candida. Pocos estudios comparan las características micológicas encontradas en la microscopía directa y el cultivo. Objetivo: Identificar las características clínicas y micológicas de la otomicosis en pacientes diabéticos. Material y método: Estudio transversal en centro hospitalario de segundo nivel. Criterios de inclusión: pacientes diabéticos con diagnóstico clínico de otomicosis. Intervención: la muestra se examinó directamente bajo el microscopio y se cultivó. Resultados: Se incluyeron 17 pacientes, 10 mujeres y 7 hombres con una edad media de 47,5 años. Los síntomas predominantes fueron hipoacusia en 91,4% (n =16), prurito en 82,4% (n =14), otorrea en 76,5% (n=13)y otalgia en 70,6% (n =12). Afección bilateral se encontró en 47,1% (n =8). Estudio directo al microscopio mostró levaduras en 94,1% (n =16) y 5,9% mostró aspergillus (n =1). Cándida fue el género más comúnmente encontrado en los cultivos y en el examen directo microscópico con 94,1% (n =16) y Candida albicans la especie más común con 88,2% (n =15). Conclusión: Candida albicans es el agente etiológico más común en pacientes diabéticos con otomicosis. Su presentación clínica más frecuente es hipoacusia, prurito y otorrea. El examen directo identificó adecuadamente a los géneros fúngicos.

ABSTRACT Introduction: Otomycosis in immunocompromised patients is characterize by its bilateral course and the predominant etiologic agent is Candida. Few studies compare the mycological features between microscopic direct exam and culture. Aim: To identify the clinical and mycological characteristics of otomycosis in diabetic patients. Material and method: Transversal study. Secondary care center. Inclusion criteria: diabetic patients with clinical diagnosis of otomycosis. Intervention: Direct examination under a microscope of the ear sample and culture. Results: We included 17 patients, 10 women, 7 men with a mean age of 47.5 years. Symptoms were hearing loss 94.1% (n = 16), pruritus 82.4% (n =14) otorrhoea 76.5% (n =13) and otalgia 70.6% (n =12). Bilateral involvement was found in 47.1% (n =8). Direct microscopic study found 94.1% of yeast (n =16) and 5.9% of Aspergillus (n =1). Candida was the most common fungal genus in culture and microscopic exam with 94.1% (n =16) of cases and Candida albicans was the most common species in 88.2% (n =15) cases. Conclusion: Candida albicans is the most common etiologic agent in diabetic patients with otomycosis. Main symptoms were hearing loss, itching and otorrhea. Direct exam correctly identified the fungal genus.

Evaluation of anti-enzyme properties of Origanum vulgare essential oil against oral Candida albicans.

This study aimed to evaluate the anti-enzymatic activity of Origanum vulgare (oregano) essential oil against 15 strains of Candida albicans. Candida albicans samples were isolated from the oral mucosa of patients with denture stomatitis treated in a Dentistry school on a public university. Preparation of the inoculum was performed with a suspension of C. albicans reactivated 24h earlier in 5mL of sterile phosphate buffer saline (PBS) adjusted to a 0.5-turbidity on the MacFarland scale (1,5×108UFC/mL). The essential oil was obtained by hydrodistillation in a Clevenger-type machine and analyzed by gas chromatography. Enzymatic assay was performed to test phospholipase anti-enzymatic properties. Chromatography analysis revealed that the main compounds present in the essential oil were 4-terpineol (41.17%), thymol (21.95%), γ-terpinene (5.91%) and carvacrol (4.71%). For the anti-enzymatic test, the statistical analysis showed that there was found statistically significant interactions between the factors time and concentration (P≤0,001). Thus, essential oil of oregano at 1%, 5% and 10% presented significant reductions in the production of the phospholipase enzyme produced by Candida albicans strains. However, the longer the incubation time of the essential oil, there is a relatively moderate reduction in its anti-enzymatic activity.

Comparison of the recovery rate of otomycosis using betadine and clotrimazole topical treatment.

INTRODUCTION: Otomycosis is a common diseases that can be associated with many complications including involvement of the inner ear and mortality in rare cases. Management of otomycosis can be challenging, and requires a close follow-up. Treatment options for otomycosis include local debridement, local and systemic antifungal agents and utilization of topical antiseptics. OBJECTIVE: This study was designed to compare the recovery rate of otomycosis using two therapeutic methods; topical betadine (Povidone-iodine) and clotrimazole. METHODS: In this single-blind clinical trial, 204 patients with otomycosis were selected using a non-probability convenient sampling method and were randomly assigned to two treatment groups of topical betadine and clotrimazole (102 patients in each group). Response to treatment was assessed at 4, 10 and 20 days after treatment. Data were analyzed using the independent t-test, Chi-Square and Fisher exact test in SPSS v.18 software, at a significance level of p<0.05. RESULTS: The results showed that out of 204 patients with otomycosis, fungi type isolated included Aspergillus in 151 cases (74%), and Candida albicans in 53 patients (26%). On the fourth day after treatment, 13 patients (13.1%) in the group treated with betadine and 10 patients (9.8%) in the group treated with clotrimazole showed a good clinical response to treatment (p=0.75). A good response to treatment was reported for 44 (43.1%) and 47 patients (46.1%) on the tenth day after the treatment (p=0.85); and 70 (68.6%) and 68 patients (67.6%) on the twentieth day after treatment (p=0.46) in the groups treated with betadine and clotrimazole, respectively. The response to treatment was thus not significantly different in the two groups. CONCLUSION: In the present study the efficacy of betadine and clotrimazole was the same for the treatment of otomycosis. The result of this study supports the use of betadine as an effective antifungal in otomycosis treatment, helping to avoid the emergence of resistant organisms.

Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant Candida albicans.

Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value.

Risk factors and outcomes of candidemia caused by Candida parapsilosis complex in a medical center in northern Taiwan.

To investigate the risk factors and outcomes associated with Candida parapsilosis candidemia, a retrospective study was conducted at a tertiary medical center in northern Taiwan. Patients with C. parapsilosis candidemia and corresponding controls with C. albicans candidemia were chosen and their demographics, comorbidities, risk factors, and clinical outcomes were reviewed. Antifungal susceptibility tests were performed using the Sensititre YeastOne colorimetric system. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to classify the genomic species. Of the 270 candidemias found in 253 patients, C. albicans was the most common Candida species isolated (43.0%), followed by C. parapsilosis (22.6%), C. tropicalis (17.4%), and C. glabrata (10.0%). The 30-day mortality of C. parapsilosis candidemia was significantly lower than that of C. albicans candidemia (21.7% vs. 53.9%, P<0.001). C. parapsilosis was positively associated with antifungal agent exposure [OR 7.261 (95% CI, 1.603-32.879), P=0.010], but negatively associated with Candida colonization [OR 0.303 (95% CI, 0.123-0.745), P=0.009], and immunosuppressant use [OR 0.264 (95% CI, 0.099-0.705), P=0.008]. In-hospital mortality was associated with the Sequential Organ Failure Assessment Score [OR 1.255 (95% CI, 1.002-1.573), P=0.048]. The clinical outcomes did not differ across genomic species and in the minimum inhibitory concentrations of fluconazole.

Impact of inappropriate antifungal therapy according to current susceptibility breakpoints on Candida bloodstream infection mortality, a retrospective analysis.

BACKGROUND: The mortality of Candida Bloodstream Infection (CBSI) remains high. Antifungal susceptibility breakpoints were recently updated for Candida species, the impact remains unknown. In this study we evaluated the impact of inappropriate antifungal treatment according to recent breakpoints on 30-day mortality of CBSI. METHODS: From June 2008 to July 2014, data on CBSI episodes from two tertiary-care centers, treated > 72 h were analyzed. Antifungal therapy and 30-day mortality were registered. Inappropriate antifungal treatment according to current Clinical & Laboratory Standards Institute (CLSI) breakpoints was adjusted with 30-day mortality-related co-variates. RESULTS: One hundred forty-nine episodes of CBSI were analyzed. The most frequent species were: C. albicans (40%), C. tropicalis (23%) and C. glabrata complex (20%). According to the 2012 CLSI, 10.7% received inappropriate treatment. The 30-day mortality was 38%; severe sepsis [Odds ratio (OR) 3.4; 95% CI 1.3-8.4], cirrhosis (OR 36; 95% CI 12.2-605), early central venous catheter removal (OR 0.23; 95% CI 0.08-0.66) and previous antifungal therapy (OR 0.15; 95%CI 0.03-0.62), were associated with 30-day mortality by multivariate analysis. Inappropriate antifungal treatment was not (OR 0.19; 95% CI 0.03-1.2). CONCLUSIONS: Appropriate antifungal therapy according to CLSI 2012 did not have an impact on mortality. Mortality of CBSI remains high due to disease severity and comorbidities; early antifungal therapy and catheter removal may reduce it.