The Effects of Tormentic Acid and Extracts from Callistemon citrinus on Candida albicans and Candida tropicalis Growth and Inhibition of Ergosterol Biosynthesis in Candida albicans.

Candida albicans and Candida tropicalis are the leading causes of human fungal infections worldwide. There is an increase in resistance of Candida pathogens to existing antifungal drugs leading to a need to find new sources of antifungal agents. Tormentic acid has been isolated from different plants including Callistemon citrinus and has been found to possess antimicrobial properties, including antifungal activity. The study aimed to determine the effects of tormentic and extracts from C. citrinus on C. albicans and C. tropicalis and a possible mode of action. The extracts and tormentic acid were screened for antifungal activity using the broth microdilution method. The growth of both species was inhibited by the extracts, and C. albicans was more susceptible to the extract compared to C. tropicalis. The growth of C. albicans was inhibited by 80% at 100 µg/ml of both the DCM: methanol extract and the ethanol: water extract. Tormentic acid reduced the growth of C. albicans by 72% at 100 µg/ml. The effects of the extracts and tormentic acid on ergosterol content in C. albicans were determined using a UV/Vis scanning spectrophotometer. At concentrations of tormentic acid of 25 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml, the content of ergosterol was decreased by 22%, 36%, 48%, and 78%, respectively. Similarly, the DCM: methanol extract at 100 µg/ml and 200 µg/ml decreased the content by 78% and 88%, respectively. A dose-dependent decrease in ergosterol content was observed in cells exposed to miconazole with a 25 µg/ml concentration causing a 100% decrease in ergosterol content. Therefore, tormentic acid inhibits the synthesis of ergosterol in C. albicans. Modifications of the structure of tormentic acid to increase its antifungal potency may be explored in further studies.

Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment.

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti-Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

Antimicrobial and antioxidant activity of catechin-3-o-rhamnoside isolated from the stem bark of Lannea kerstingii Engl. and K. Krause (Anacardiaceae).

Various epidemiological researches have shown that consumption of vegetables and fruits are essential to maintain health and prevent diseases but the emergence of more and more drug resistance bacteria has led to high mortality. Thus the study of the antimicrobial and antioxidant activities of a flavonoid (Catechin-3-o-rhamnoside) isolated for the first time from Lannea kerstingii. Catechin-3-o-rhamnoside was isolated using dry vacuum liquid chromatography. It was characterized using 1H-NMR, 13C-NMR and 2D NMR spectra. The antimicrobial activity was determined using agar diffusion and broth dilution method. Antioxidant activity was determined through reaction of the compound with DPPH radical. The compound was active against, Methicillin Resistant Staphylococcus aureus, S. aureus, B. subtilis, E. coli, K. pneumoniae, S. typhi, S. dysentariae, C. albicans and C. tropicalis with zone of inhibition ranging from 22.0±0.1 to 35.0±0.2mm and inactive against vancomycin resistant enterococci, Proteus mirabilis and C. ulcerans. The MIC ranged from 6.25 to 12.5µg/ml while the MBC/MFC ranged from 12.5 to 50.0µg/ml. The compound showed a high radical scavenging activity with EC50 of 46.87µg/ml. These results show a potential lead drug for resistant bacteria and natural antioxidants.

Lanosterol 14α-demethylase (CYP51)/histone deacetylase (HDAC) dual inhibitors for treatment of Candida tropicalis and Cryptococcus neoformans infections.

Invasive fungal infections remain a challenge due to lack of effective antifungal agents and serious drug resistance. Discovery of antifungal agents with novel antifungal mechanism is important and urgent. Previously, we designed the first CYP51/HDAC dual inhibitors with potent activity against resistant Candida albicans infections. To better understand the antifungal spectrum and synergistic mechanism, herein new CYP51/HDAC dual inhibitors were designed which showed potent in vitro and in vivo antifungal activity against C. neoformans and C. tropicalis infections. Antifungal mechanism studies revealed that the CYP51/HDAC dual inhibitors acted by inhibiting various virulence factors of C. tropicalis and C. neoformans and down-regulating resistance-associated genes. This study highlights the potential of CYP51/HDAC dual inhibitors as a promising strategy for the discovery of novel broad-spectrum antifungal agents.

Molecular epidemiology of Candida tropicalis isolated from urogenital tract infections.

Candida tropicalis is a common human pathogenic yeast, and its molecular typing is important for studying the population structure and epidemiology of this opportunistic yeast, such as epidemic genotype, population dynamics, nosocomial infection, and drug resistance surveillance. In this study, the antifungal susceptibility test and multilocus sequence typing (MLST) analysis were carried out on C. tropicalis from central China. Among 64 urogenital isolates, 45 diploid sequence types (DST) were found, of which 20 DSTs (44.4%) were new to the central database. The goeBURST analysis showed that CC1 (clonal complex) was the only azole-resistant (100%, 10/10) cluster in Wuhan, which was composed of DST546, DST225, DST376, and DST506, and most of the strains (90%, 9/10) were isolated from the urinary tract. Potential nosocomial infections were mainly caused by CC1 strains. The azole resistance rate of urinary isolates (50.0%, 21/42) was higher than that of vaginal isolates (27.3%, 6/22). The genotype diversity and novelty of vaginal isolates were higher than those of urinary isolates. C. tropicalis population in Wuhan was genetically diverse and divergent from that seen in other countries. In this study, there were significant differences in genotype and azole susceptibility between urine and vaginal strains. The azole-resistant cluster (CC1) found in urine is of great significance for the clinical treatment and prevention of nosocomial infection. The newly discovered DSTs will contribute to further study the similarity, genetic relationship, and molecular epidemiology of C. tropicalis worldwide.

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms.

The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules derived from natural products. Herein, crotoxin (CTX), the main toxin of Crotalus durissus terrificus venom, was challenged against Candida tropicalis (CBS94) and Candida dubliniensis (CBS7987) strains by in vitro antimicrobial susceptibility tests. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and inhibition of biofilm formation were evaluated after CTX treatment. In addition, CTX-induced cytotoxicity in HaCaT cells was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. Native CTX showed a higher antimicrobial activity (MIC = 47 µg/mL) when compared to CTX-containing mouthwash (MIC = 750 µg/mL) and nystatin (MIC = 375 µg/mL). Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 µg/mL) when compared to nystatin (IC100 > 47 µg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains.

Effect of initial antifungal therapy on mortality among patients with bloodstream infections with different Candida species and resistance to antifungal agents: A multicentre observational study by the Turkish Fungal Infections Study Group.

This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32-3.57); P = 0.002], renal failure [OR = 2.4 (1.41-3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22-3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06-2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36-0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving.

In vitro anticandidal potency of Syzygium aromaticum (clove) extracts against vaginal candidiasis.

BACKGROUND: Candida vaginitis is a global health hazard that increases morbidity among women of childbearing age. Recent studies have revealed a high incidence of drug-resistant Candida strains. Additionally, treating Candida vulvovaginitis during pregnancy is challenging as antifungal therapy is associated with fetal abnormalities. Hence, it is important to develop novel therapeutic strategies to treat vulvovaginal candidiasis. METHODS: In this study, we used the disc diffusion method to evaluate the anticandidal activity of different Syzygium aromaticum extracts (methanol, ethyl acetate, n-hexane, and diethyl ether) against C. albicans, C. glabrata, and C. tropicalis. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of different S. aromaticum extracts was performed to determine active components exhibiting anticandidal activity. Cytotoxicity of different clove extracts against the HUH7 cell line was evaluated. RESULTS: The ethyl acetate extract exhibited the highest antifungal activity against C. albicans, C. glabrata, and C. tropicalis with inhibition zone diameters of 20.9, 14.9, and 30.7 mm, respectively. The minimum inhibitory concentration of the S. aromaticum ethyl acetate extract was 250 µg/disc against C. tropicalis, and 500 µg/disc against C. albicans and C. glabrata, while the minimum fungicidal concentration was 0.5 mg/disc against C. tropicalis and 1 mg/disc against the C. albicans and C. glabrata. GC-MS analysis of the ethyl acetate extract revealed the main bioactive compound as eugenol (58.88%), followed by eugenyl acetate (23.86%), trans-caryophyllene (14.44%), and α-humulene (1.88%). The cytotoxicity assay indicated that the diethyl ether extract demonstrated the lowest toxicological effect against the HUH7 cell line, with a relative IC50 of 62.43 µg/ml; the methanolic extract demonstrated a higher toxicity (IC50, 24.17 µg/ml). CONCLUSION: As the S. aromaticum extract exhibited high antifungal activity at low concentrations, it can be a potential source of natural antifungal drugs.

Selection and evaluation of appropriate reference genes for RT-qPCR based expression analysis in Candida tropicalis following azole treatment.

Candida tropicalis arises as one of the predominant non-Candida albicans Candida (NCAC) species causing invasive candidiasis in Asian countries. A rise in reports of C. tropicalis with a parallel increase in fluconazole resistance has also been observed. The genes and underlying pathways associated with azole antifungal resistance in C. tropicalis is still not properly understood. The RT-qPCR is the most promising approach for expression analysis of target genes to understand the mechanisms of resistance. The reliability and reproducibility of this technique depend on the selection of suitable reference genes for the normalization in expression study. The present study investigated the expression stability levels of ten genes including ACT1, EF1, GAPDH, PGK1, RDN5.8, RDN18, RDN28, SDHA, TUB1, and UBC13 for their suitability in fluconazole treated/untreated C. tropicalis. The stability levels of these genes were examined by the ∆∆CT, ΔCT, Pfaffl methods and five independent software including hkgFinder, geNorm, NormFinder, BestKeeper, and RefFinder software. We report, the EF1 and ACT1 were the most stable reference genes for normalization and can be used for the gene expression analysis in C. tropicalis. To the best of our knowledge, our study is the first to select and validate the reference genes in C. tropicalis for RT-qPCR based expression analysis.

Thymus vulgaris essential oil and thymol inhibit biofilms and interact synergistically with antifungal drugs against drug resistant strains of Candida albicans and Candida tropicalis.

Role of biofilm in disease development and enhance tolerance to antifungal drugs among Candida species has necessitated search for new anti-fungal treatment strategy. Interference in pathogenic biofilm development by new antifungal compounds is considered as an attractive anti-infective strategy. Therefore, the objective of this study was to evaluate Thymus vulgaris essential oil and its major active compound, thymol for their potential to inhibit and eradicate biofilms alone and in combination with antifungal drugs against Candida spp. with especial reference to Candida tropicalis. Anti-candidal efficacy of T. vulgaris and thymol in terms of minimum inhibitory concentration (MIC) was first determined to select the sub-MICs against C. albicans and C. tropicalis. Biofilm formation in the presence and absence of test agents was determined in 96-well microtiter plate by XTT reduction assay and effect of essential oils at sub-MICs of the test agents on biofilm development on glass surface was analysed by light and scanning electron microscopy. Synergistic interaction between essential oils and antifungal drugs were studied by checkerboard method. Effect of sub-MIC of T. vulgaris (0.5×MIC) and thymol (0.5×MIC) on biofilm formation showed a significant reduction (P<0.05) in biofilms. Light microscopy and SEM studies revealed disaggregation and deformed shape of C. albicans biofilm cells and reduced hyphae formation in C. tropicalis biofilm cells at sub-MICs of thymol. Significant effect of T. vulgaris and thymol was also recorded on pre-formed biofilms of both C. albicans and C. tropicalis. T. vulgaris and thymol also showed synergy with fluconazole against both in planktonic and biofilm mode of growth of C. albicans and C. tropicalis. However, synergy with amphotericin B is clearly evident only in planktonic Candida cells. Thyme oil and thymol alone or in combination with antifungal drugs can act as promising antibiofilm agent against drug resistant strains of Candida species and needs further in vivo study to synergise its therapeutic efficacy.

Antifungal and biofilm inhibitory effect of Cymbopogon citratus (lemongrass) essential oil on biofilm forming by Candida tropicalis isolates; an in vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemongrass) essential oil has been widely used as a traditional medicine and is well known for antimicrobial properties. Therefore, it might be a potent anti-infective and biofilm inhibitive against Candida tropicalis infections. Until now, no ideal coating or cleaning method based on an essential oil has been described to prevent biofilm formation of Candida strains on silicone rubber maxillofacial prostheses, voice prostheses and medical devices susceptible to C. tropicalis infections. AIM OF THE STUDY: To investigate the antifungal and biofilm inhibitory effects of Cymbopogon citratus oil. Clinical isolates of C. tropicalis biofilms on different biomaterials were used to study the inhibitory effect. MATERIALS AND METHODS: The efficacy of Cymbopogon citratus, Cuminum cyminum, Citrus limon and Cinnamomum verum essential oils were compared on biofilm formation of three C. tropicalis isolates on 24 well polystyrene plates. C. citratus oil coated silicone rubber surfaces were prepared using hypromellose ointment as a vehicle. The antifungal tests to determine minimum inhibitory and minimum fungicidal concentrations were assessed by a microbroth dilution method and biofilm formation was determined by a crystal violet binding assay. RESULTS: C. tropicalis strains formed more biofilm on hydrophobic materials than on hydrophilic glass. C. citratus oil showed a high antifungal effect against all C. tropicalis strains. For comparison, C. limon oil and C. cyminum oil showed minor to no killing effect against the C. tropicalis strains. C. citratus oil had the lowest minimal inhibitory concentration of all essential oils tested and inhibited biofilm formation of all C. tropicalis strains. C. citratus oil coating on silicone rubber resulted in a 45-76% reduction in biofilm formation of all C. tropicalis strains. CONCLUSION: Cymbopogon citratus oil has good potential to be used as an antifungal and antibiofilm agent on silicone rubber prostheses and medical devices on which C. tropicalis biofilms pose a serious risk for skin infections and may cause a shorter lifespan of the prosthesis.

Clonality of Fluconazole-Nonsusceptible Candida tropicalis in Bloodstream Infections, Taiwan, 2011-2017.

Candida tropicalis is the leading cause of non-C. albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505-7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.

Repurposing of Ribavirin as an Adjunct Therapy against Invasive Candida Strains in an In Vitro Study.

The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against Candida spp. Primary screening of a Prestwick Chemical library against Candida albicans ATCC 90028 and fluconazole-resistant Candida albicans strains was performed. Subsequently, we evaluated the responses of 100 Candida sp. strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin resistance. We studied time-kill curves and performed a checkerboard assay for a ribavirin-antifungal combination study. Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had antifungal activity in vitro against 63 Candida strains, including strains of C. albicans, C. parapsilosis, and C. tropicalis, with MICs ranging from 0.37 to 3.02 µg/ml, while MICs for C. krusei, C. glabrata, C. lusitaniae, and some C. albicans strains remained high (≥24.16 µg/ml). No relation was observed between efflux pump activity and ribavirin resistance. Ribavirin exhibited fungistatic activity against multidrug-resistant (MDR) C. albicans and fungicidal activity against a C. parapsilosis strain. In addition, ribavirin acted synergistically with azoles against Candida strains for which ribavirin MICs were <24.4 µg/ml. This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti-Candida drug.

Mentha piperita L. essential oil inactivates spoilage yeasts in fruit juices through the perturbation of different physiological functions in yeast cells.

This study evaluated the efficacy of the essential oil from Mentha piperita L. (MPEO) to inactivate cells of the potentially spoilage yeasts Candida albicans, Candida tropicalis, Pichia anomala and Saccharomyces cerevisiae in cashew, guava, mango and pineapple juices during 72 h of refrigerated storage. Damage in different physiological functions caused by MPEO in S. cerevisiae in cashew and guava juices were investigated using flow cytometry (FC). The effects of the incorporation of an effective anti-yeast MPEO dose on sensory characteristics of juices were also evaluated. MPEO displayed minimum inhibitory concentration of 1.875 µL/mL against all tested yeasts. A >5 log reduction in counts of C. albicans, P. anomala and S. cerevisiae was observed in cashew and guava juices with 7.5 and 3.75 µL/mL MPEO. Tested MPEO concentrations (1.875, 3.75 and 7.5 µL/mL) were not effective to cause >5 log reduction in counts of target yeasts in mango and pineapple juices during 72 h of exposure. Incorporation of 1.875 µL/mL MPEO in cashew and guava juices strongly compromised membrane permeability, membrane potential, enzymatic activity and efflux pump activity in S. cerevisiae cells. This same MPEO concentration did not affect appearance, odor and viscosity in fruit juices, but negatively affected their taste and aftertaste. These results show the efficacy of MPEO to inactivate potentially spoilage yeasts in fruit juices through disturbance of different physiological functions in yeast cells. However, the combined use of MPEO with other technologies should be necessary to decrease its effective anti-yeast dose in fruit juices and, consequently, the possible negative impacts on specific sensory properties of these products.

Clinical characteristics of Candida tropicalis fungaemia with reduced triazole susceptibility in Taiwan: a multicentre study.

Candida tropicalis is the second most common Candida species causing fungaemia in Taiwan, and decreased susceptibility to fluconazole has been reported. This study analysed the clinical characteristics of adult patients with C. tropicalis fungaemia and the antifungal susceptibilities of isolates at five tertiary hospitals in Taiwan (1 July 2011 to 30 June 2014). A standardised case record form was used retrospectively to collect demographic, clinical and microbiological characteristics, antifungal treatment and outcomes. MICs of non-duplicate isolates were determined using SensititreTM YeastOneTM and were interpreted using cut-off values recommended by the CLSI. A total 248 patients were diagnosed over the study period; 30-day crude mortality was 52.0%. Multivariate analysis showed that high Charlson comorbidity index ≥4 (OR = 2.09, 95% CI 1.22-3.59; P = 0.008), neutropenia (OR = 4.61, 95% CI 1.42-15.00; P = 0.011) and treatment with an azole-based regimen (OR = 0.39, 95% CI 0.17-0.90; P = 0.028) were significantly associated with 30-day mortality. A total of 33.9% of isolates were non-susceptible to fluconazole (MIC50, 2 mg/L; MIC90, 16 mg/L; MIC range, 0.25 to >256 mg/L), whilst 56.9% to voriconazole (MIC50, 0.25 mg/L; MIC90, 1 mg/L; MIC range, 0.015 to >8 mg/L) according to CLSI clinical breakpoints. There was no significant correlation between overall mortality and MICs of fluconazole or voriconazole. This study showed high mortality in patients with C. tropicalis fungaemia, and azole-based antifungal treatment could improve outcomes regardless of fluconazole MICs of infecting isolates compared with patients without any treatment within 48 h.

Delay in effective therapy in anidulafungin-resistant Candida tropicalis fungaemia: Potential for rapid prediction of antifungal resistance with whole-genome-sequencing.

OBJECTIVES: This study investigated the feasibility of using whole-genome sequencing (WGS) for the prediction of antifungal resistance in anidulafungin-resistant Candida tropicalis candidaemia isolates. METHODS: Next-generation sequencing was performed for three anidulafungin-resistant C. tropicalis isolates on an Illumina MiSeq system with in-house bioinformatics analysis. RESULTS: Mutations in Fks1p associated with anidulafungin resistance were identified. Other mutations associated with varying levels of phenotypic resistance to fluconazole were also identified. CONCLUSIONS: These data demonstrate the potential to predict antifungal resistance using WGS. With improving technology, real-time WGS may be used for tailoring effective antifungal therapy in patients with candidaemia.

Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue.

This work illustrates a new role for the membranotropic peptide gH625 and its derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed biofilms composed of Candida and bacterial species cause frequently infections and failure of medical silicone devices and also show a major drug resistance than single-species biofilms. Inhibition and eradication of biofilms were evaluated by complementary methods: XTT-reduction, and crystal violet staining (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide, strongly inhibited formation of mixed biofilms of clinical isolates of C. tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm architecture, interfering with cell adhesion and polymeric matrix, as well as eradicated the long-term polymicrobial biofilms on silicone surface.

Development of Echinocandin Resistance in Candida tropicalis following Short-Term Exposure to Caspofungin for Empiric Therapy.

Isolation of two echinocandin-resistant Candida tropicalis strains from endotracheal secretions of a patient following short-term exposure to caspofungin is described. Both strains exhibited resistance to echinocandins by Etest and reference broth microdilution, showing a homozygous S645P mutation within the hot spot 1 (HS-1) region of FKS1 and belonging to a unique multilocus sequence type. Other C. tropicalis isolates collected from patients in the same intensive care unit within a 60-day period were susceptible to echinocandins and contained wild-type FKS1 sequences.

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.

Antifungal activity of the essential oil of cymbopogon citratus (DC) stapf: an in vitro study

Aim. to evaluate the antifungal potential of the essential oil of cymbopogon citratus by determining the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) for candida albicans (ATCC 90029), candida albicans (CBS 562), candida tropicalis (ATCC 705) and candida tropicalis strains (CBS 94), as well as to analyze the possible mechanism of action of the oil through the addition of sorbitol to the culture medium. methods. for the MIC determination, inocula were previously adjusted through spectrophotometry and 100µL were added to the wells of plates already containing the culture medium and 100µL of the serial dilutions of the oil, incubating them in aerobiosis for 24 hours, with subsequent staining by 1 percent TCT. for the MFC, 50µL of the supernatant from the MIC assay wells were dripped onto petri dishes and incubated in aerobiosis for 24 hours. tests were performed in triplicate and data analysed by descriptive statistics. results. It was determined that the MIC for C. albicans was 125 µg/mL while MIC for C. tropicalis was 250 µg/mL, with the essential oil presenting fungicidal effect for both analyzed yeasts. conclusion. the essential oil of cymbopogon citratus does not act at the cellular wall level and demonstrated an antimicrobial effect on candida albicans and candida tropicalis, therefore acting as a fungicide.