Antifungal susceptibility and virulence determinants profile of candida species isolated from patients with candidemia.

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.

Chinese Chronic Mucocutaneous Candidiasis: A Case Report Series.

Chronic Mucocutaneous Candidiasis (CMC) is a rare immunodeficiency disease characterized by chronic or recurrent superficial Candida infections on the skin, nail, and mucous membranes. Here, we present four Chinese patients with CMC who manifested oral mucosal leukoplakia and nail thickening during early childhood, all displaying fissured tongue lines. The causative pathogens isolated from their oral mucosa and nails were identified as C. albicans and C. parapsilosis through morphology and molecular sequencing. Notably, among the four patients, one presented with vitiligo, while another had hypothyroidism. We have also conducted a review of reported cases of CMC in China and worldwide over the last five years, highlighting potential approaches for diagnosis and treatment. The current molecular evidence in the literature suggests potential for the development of early diagnosis methods, such as screening genetic variables on STAT1 and STAT3. Additionally, potential treatment avenues, including gene-targeted analogues and GM-CSF analogues, could be explored in conjunction with traditional antifungal therapy.

Inherited CARD9 Deficiency Due to a Founder Effect in East Asia.

Autosomal recessive CARD9 deficiency can underly deep and superficial fungal diseases. We identified two Japanese patients, suffering from superficial and invasive Candida albicans diseases, carrying biallelic variants of CARD9. Both patients, in addition to another Japanese and two Korean patients who were previously reported, carried the c.820dup CARD9 variant, either in the homozygous (two patients) or heterozygous (three patients) state. The other CARD9 alleles were c.104G > A, c.1534C > T and c.1558del. The c.820dup CARD9 variant has thus been reported, in the homozygous or heterozygous state, in patients originating from China, Japan, or South Korea. The Japanese, Korean, and Chinese patients share a 10 Kb haplotype encompassing the c.820dup CARD9 variant. This variant thus originates from a common ancestor, estimated to have lived less than 4,000 years ago. While phaeohyphomycosis caused by Phialophora spp. was common in the Chinese patients, none of the five patients in our study displayed Phialophora spp.-induced disease. This difference between Chinese and our patients probably results from environmental factors. (161/250).

Exploring the dynamics of mixed-species biofilms involving Candida spp. and bacteria in cystic fibrosis.

Cystic fibrosis (CF) is an inherited disease that results from mutations in the gene responsible for the cystic fibrosis transmembrane conductance regulator (CFTR). The airways become clogged with thick, viscous mucus that traps microbes in respiratory tracts, facilitating colonization, inflammation and infection. CF is recognized as a biofilm-associated disease, it is commonly polymicrobial and can develop in biofilms. This review discusses Candida spp. and both Gram-positive and Gram-negative bacterial biofilms that affect the airways and cause pulmonary infections in the CF context, with a particular focus on mixed-species biofilms. In addition, the review explores the intricate interactions between fungal and bacterial species within these biofilms and elucidates the underlying molecular mechanisms that govern their dynamics. Moreover, the review addresses the multifaceted issue of antimicrobial resistance in the context of CF-associated biofilms. By synthesizing current knowledge and research findings, this review aims to provide insights into the pathogenesis of CF-related infections and identify potential therapeutic approaches to manage and combat these complex biofilm-mediated infections.

A Systematic Review of Denture Stomatitis: Predisposing Factors, Clinical Features, Etiology, and Global Candida spp. Distribution.

Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20-67%. Both industrially developed and impoverished nations are affected by the illness. DS is often associated with ill-fitting dentures or a fungal infection with Candida spp. Candida is normally found in the oral cavity microbiota, but it can be harmful to the health of elderly people with underlying diseases. Therefore, the purpose of the present study is to offer the most recent information about the epidemiology, etiology, and global distribution of Candida species associated with DS through a systematic review. Several databases, including Medline, Web of Science, and Scopus, were used to conduct an extensive search of the literature published in the previous 20 years. The selection of studies was performed by two authors. The extracted data were as follows: author, year of publication, country, sample, frequency of DS, method of diagnosing stomatitis, species of Candida, risk factors, and etiology of the disease. The JBI Critical appraisal tools were used to assess the quality of the studies. Eventually, twenty-eight studies were included in the systematic review. Twenty-one studies investigated DS, while seven studies examined Candida colonization in patients using removable dentures. The results show that the main causes of DS include the type of dentures, continuous wearing of dentures, and the formation of a Candida biofilm, which is facilitated by poor dental hygiene. Additionally, previous studies have pinpointed the significance of the salivary flow, saliva composition, and salivary pH. The findings of the current review indicate that it is crucial to monitor denture wearers for the appearance of DS, especially the patients whose immunity has been impaired due to a systemic condition. Finally, frequent follow-ups should include a clinical examination and microbial swabs of the palatal mucosa and the mucosal surface of the denture.

Antimicrobial and Antibiofilm Potential of Green-Synthesized Graphene-Silver Nanocomposite against Multidrug-Resistant Nosocomial Pathogens.

Hospital-acquired infections (HAIs) pose a significant risk to global health, impacting millions of individuals globally. These infections have increased rates of morbidity and mortality due to the prevalence of widespread antimicrobial resistance (AMR). Graphene-based nanoparticles (GBNs) are known to possess extensive antimicrobial properties by inflicting damage to the cell membrane, suppressing virulence, and inhibiting microbial biofilms. Developing alternative therapies for HAIs and addressing AMR can be made easier and more affordable by combining nanoparticles with medicinal plants harboring antimicrobial properties. Hence, this study was undertaken to develop a novel graphene-silver nanocomposite via green synthesis using Trillium govanianum plant extract as a reducing agent. The resulting nanocomposite comprised silver nanoparticles embedded in graphene sheets. The antibacterial and antifungal properties of graphene-silver nanocomposites were investigated against several nosocomial pathogens, namely, Candida auris, Candida glabrata, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nanocomposite displayed broad-range antimicrobial potential against the test pathogens, with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125.0 µg/mL, and biofilm inhibition up to 80-96%. Moreover, nanocomposite-functionalized urinary catheters demonstrated hemocompatibility towards sheep erythrocytes and imparted anti-fouling activity to the biomaterial, while also displaying biocompatibility towards HEK 293 cells. Collectively, this investigation highlights the possible application of green-synthesized GBNs as an effective alternative to conventional antibiotics for combating multidrug-resistant pathogens.

Phytolacca tetramera berries extracts and its main constituents as potentiators of antifungal drugs against Candida spp.

BACKGROUND: Extensive antifungal drug use has enhanced fungal resistance, resulting in persistent mycoses. Combining antifungal plant extracts/compounds with these drugs offers good alternatives to increase the activity of both partners, minimize side effects, and overcome drug resistance. In our previous study, Phytolacca tetramera berries extracts demonstrated activity against Candida spp., correlating with the amount of the main constituent phytolaccoside B and its genin, phytolaccagenin. The extracts and phytolaccagenin altered the fungal plasma membrane by binding to ergosterol, whereas phytolaccoside B increased chitin synthase activity. However, the presence of triterpenoid saponins in Phytolacca spp. has been linked to acute toxicity in humans. PURPOSE: This study aimed to evaluate combinations of P. tetramera berries extracts, phytolaccoside B and phytolaccagenin, together with commercial antifungals [amphotericin B, fluconazole, itraconazole, posaconazole, and caspofungin] against Candida albicans and Candida glabrata, to find synergistic effects with multi-target actions, in which the doses of both partners are reduced, and therefore their toxicity. Additionally, we intended to explore their anti-virulence capacity, thereby hindering the development of drug-resistant strains. METHODS: The effects of these combinations were evaluated using both the checkerboard and isobologram methods. Fractional Inhibitory Concentration Index and Dose Reduction Index were calculated to interpret the combination results. To confirm the multi-target effect, studies on mechanisms of action of synergistic mixtures were performed using ergosterol-binding and quantification assays. The ability to inhibit Candida virulence factors, including biofilm formation and eradication from inert surfaces, was also evaluated. Quantification of active markers was performed using a validated UHPLC-ESI-MS method. RESULTS: Eight synergistic combinations of P. tetramera extracts or phytolaccagenin (but not phytolaccoside B) with itraconazole or posaconazole were obtained against C. albicans, including a resistant strain. These mixtures acted by binding to ergosterol, decreasing its whole content, and inhibiting Candida biofilm formation in 96-well microplates and feeding tubes in vitro, but were unable to eradicate preformed biofilms. CONCLUSIONS: This study demonstrated the synergistic and anti-virulence effects of P. tetramera berries extracts and phytolaccagenin with antifungal drugs against Candida spp., providing novel treatment avenues for fungal infections with reduced doses of both natural products and commercial antifungals, thereby mitigating potential human toxicity concerns.

Antifungal activity of Caryocar brasiliense camb. Alone or along with antifungal agents against multidrug-resistant Candida auris.

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.

Evaluation of mixed biofilm production by Candida spp. and Staphylococcus aureus strains co-isolated from cystic fibrosis patients in northwest Algeria.

Cystic fibrosis patients' lungs are chronically colonized by multiple microbial species capable of forming biofilms. This study aimed to characterize the polymicrobial biofilm formed by Candida spp. and S. aureus, co-isolated from sputum samples of cystic fibrosis patients regarding microbial density, metabolic activity, and structure. 67 samples from 28 patients were collected with a 96% alteration rate. 34% showed alterations by both Candida spp. and Gram-positive bacteria, predominantly Candida spp. and S. aureus in 77% of cases, accounting for 6 associations. Biofilm biomass was quantified using the crystal violet assay, and metabolic activity was assessed using the MTT reduction assay. Scanning electron microscopy analyzed the C. tropicalis/S. aureus24 biofilm architecture. Candida spp. isolates demonstrated the ability to form mixed biofilms with S. aureus. The C. tropicalis/S. aureus24 association exhibited the highest production of biofilm and metabolic activity, along with the C. albicans17/C. rugosa/S. aureus7 in both single and mixed biofilms.

Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood. Objectives: We aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization. Methods: Sensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1). Results: Sensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp. Conclusion: We conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns.

Evaluation of the antifungal effect of plant extracts on oral Candida spp. - a critical methodological analysis of the last decade.

INTRODUCTION: In 2022, the World Health Organization published a report encouraging researchers to focus on Candida spp. to strengthen the global response to fungal oral infections and antifungal resistance. In the context of innovative research, it seems pertinent to investigate the antifungal potential of natural extracts of plants and the methodology involved in the recent reports. The aim of this systematic review is to identify the current state of in vitro research on the evaluation of the ability of plant extracts to inhibit Candida spp. MATERIAL AND METHODS: A bibliographic search has been developed to on a 10-year period to identify which plant extracts have an antifungal effect on the Candida spp. found in the oral cavity. RESULTS: A total of 20 papers were reviewed and fulfilled all the selection criteria and were included in the full data analysis. DISCUSSION: Plants have been tested in a wide range of states - whole extracts, extraction of particular components such as flavonoids or polyphenols, or even using the plant to synthesize nanoparticles. Of forty-five plants tested, five of them did not show any effect against Candida spp., which weren't part of the same family. There is a wide range of plant that exhibit antifungal proprieties. CONCLUSION: Many plants have been tested in a wide range of states - whole extracts, extraction of components such as flavonoids or polyphenols, or even using the plant to synthetize nanoparticles. The combination of plants, the addition of plants to a traditional antifungal and the interference with adhesion provided by some plants seem to be promising strategies. Nonetheless, on contrary to drugs, there is a critical lack of standardization on methodologies and protocols, which makes it difficult to compare data and, consequently, to conclude, beyond doubts, about the most promising plants to fight Candida spp. oral infections.

Galleria mellonella as a Model for the Study of Fungal Pathogens: Advantages and Disadvantages.

The study of pathogenicity and virulence of fungal strains, in vivo in the preclinical phase, is carried out through the use of animal models belonging to various classes of mammals (rodents, leproids, etc.). Although animals are functionally more similar to humans, these studies have some limitations in terms of ethics (animal suffering), user-friendliness, cost-effectiveness, timing (physiological response time) and logistics (need for adequately equipped laboratories). A good in vivo model must possess some optimal characteristics to be used, such as rapid growth, small size and short life cycle. For this reason, insects, such as Galleria mellonella (Lepidoptera), Drosophila melanogaster (Diptera) and Bombyx mori (Lepidoptera), have been widely used as alternative non-mammalian models. Due to their simplicity of use and low cost, the larvae of G. mellonella represent an optimal model above all to evaluate the virulence of fungal pathogens and the use of antifungal treatments (either single or in combination with biologically active compounds). A further advantage is also represented by their simple neuronal system limiting the suffering of the animal itself, their ability to survive at near-body ambient temperatures as well as the expression of proteins able to recognise combined pathogens following the three R principles (replacement, refinement and reduction). This review aims to assess the validity as well as the advantages and disadvantages of replacing mammalian classes with G. mellonella as an in vivo study model for preclinical experimentation.

The Influence of L-Lysine-Alpha-Oxidase on the Biofilm Formation of Opportunistic Microorganisms Associated with Inflammatory Diseases of the Urinary Tract.

Urinary tract infections occupy a special niche among diseases of infectious etiology. Many microorganisms associated with urinary tract infections, such as Klebsiella oxytoca, Enterococcus spp., Morganella morganii, Moraxella catarrhalis, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Staphylococcus spp., and Candida spp., can form biofilms. The aim of this research was to study the effect of the enzyme L-lysine-Alpha-oxidase (LO) produced by the fungus Trichoderma harzianum Rifai on the biofilm formation process of microorganisms associated with urinary tract infections. Homogeneous LO showed a more pronounced effect than the culture liquid concentrate (cCL). When adding samples at the beginning of incubation, the maximum inhibition was observed in relation to Enterococcus faecalis 5960-cCL 86%, LO 95%; Enterococcus avium 1669-cCL 85%, LO 94%; Enterococcus cloacae 6392-cCL 83%, LO-98%; and Pseudomonas aeruginosa 3057-cCL 70%, LO-82%. The minimum inhibition was found in Candida spp. Scanning electron microscopy was carried out, and numerous morphological and structural changes were observed in the cells after culturing the bacterial cultures in a medium supplemented with homogeneous LO. For example, abnormal division was detected, manifesting as the appearance of joints in places where the bacteria diverge. Based on the results of this work, we can draw conclusions about the possibility of inhibiting microbial biofilm formation with the use of LO; especially significant inhibition was achieved when the enzyme was added at the beginning of incubation. Thus, LO can be a promising drug candidate for the treatment or prevention of infections associated with biofilm formation.

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence.

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

Molecular Pathway, Epidemiological Data and Treatment Strategies of Fungal Infection (Mycoses): A Comprehensive Review.

The recent increase in fungal infections is a health crisis. This surge is directly tied to the increase in immunocompromised people caused by changes in medical practice, such as the use of harsh chemotherapy and immunosuppressive medicines. Immunosuppressive disorders such as HIV have exacerbated the situation dramatically. Subcutaneous or superficial fungal infections can harm the skin, keratinous tissues, and mucous membranes. This category includes some of the most common skin disorders that impact millions of people worldwide. Despite the fact that they are seldom fatal, they can have a catastrophic impact on a person's quality of life and, in rare situations, spread to other people or become obtrusive. The majority of fungal infections under the skin and on the surface are simply and quickly cured. An opportunistic organism that preys on a weak host or a natural intruder can both result in systemic fungal infections. Furthermore, it might be exceedingly lethal and dangerous to one's life. Dimorphic fungi may pose a hazard to healthy populations that are not exposed to endemic fungi. Increased surveillance, the availability of quick, noninvasive diagnostic tests, monitoring the emergence of antifungal medication resistance, and research on the pathophysiology, prevention, and management of fungal infections are just a few potential solutions to these new health problems. The goal of this review is to summarize the data available for fungal infections and the different therapies which are involved in their treatment. Additionally, it also summarizes the molecular and scientific data of the plants which contain anti-fungal activity. Data are acquired using Google, PubMed, Scholar, and other online sources.

Co-colonization of methicillin-resistant Staphylococcus aureus and Candida spp. in children with malignancies.

This study aimed to evaluate the interaction between methicillin-resistant Staphylococcus aureus(MRSA) and Candida spp. in the oral cavity of children with malignancies under chemotherapy. We evaluated the expression level of Als3p and mecA in Candida spp. and MRSA strains in both single colonization and co-colonization condition. Oral and nasal samples were collected by dry sponge swabs in 10 ml of sterile phosphate-buffered saline. The MRSA and Candida spp. was confirmed using the PCR method and mecA and Als3p genes, respectively. The SYBR Green-based quantitative real-time PCR was used to evaluate the relative expression levels of mecA and Als3p genes in MRSA and Candida spp., respectively. The frequency of S. aureus in oral-only and nasal-only swab samples were 14.1% (n = 24/170). 58.3% (n = 14/24) and 29.2% (n = 7/24) of S. aureus isolated from oral and nasal samples were MRSA, respectively. Among Candida species, C. albicans (n = 28/170; 16.5%) had the highest frequency. The oral co-colonization of MRSA and Candida spp. was detected in 4.7% (n = 8/170) patients. The overall average of gene expression levels among all Candida spp. and MRSA isolates indicated that the mecA and Als3p genes expression increased six and two times in co-colonization conditions compared to single colonization conditions, respectively. Our findings revealed the importance of polymicrobial infection in clinical settings and stated that it is possible that Candida spp. facilitates the infection of S. aureus and can lead to systemic infection in co-colonized patients.

Evaluation of Biofilm Production and Antifungal Susceptibility to Fluconazole in Clinical Isolates of Candida spp. in Both Planktonic and Biofilm Form.

Candida spp. are an important opportunistic pathogen that can represent a possible cause of severe infections, especially in immunocompromised individuals. The clinical impact of Candida spp. depends, in part, on the ability to form biofilms, communities of nestled cells into the extracellular matrix. In this study, we compared the biofilm formation ability of 83 strains of Candida spp. isolated from blood cultures and other materials, such as respiratory samples, urine, and exudate, and their sensitivity to fluconazole (FLZ). Strains were divided into tertiles to establish cut-offs to classify isolates as low, moderate, or high biofilm producers (<0.26, 0.266-0.839, >0.839) and biofilms with low, moderate, or high metabolic activity (<0.053, 0.053-0.183, >0.183). A non-linear relationship between biofilm production and metabolic activity was found in C. glabrata and C. tropicalis. In addition, the increase in minimum biofilm eradication concentrations (MBEC50) compared to the Minor Inhibitory Concentration (PMIC) of the planktonic form in Candida spp. confirms the role of biofilm in the induction of resistance to FLZ.

Questioning the 14-day dogma in candidemia treatment duration.

The growing threat of antimicrobial resistance (AMR) is a global concern. With AMR directly causing 1.27 million deaths in 2019 and projections of up to 10 million annual deaths by 2050, optimising infectious disease treatments is imperative. Prudent antimicrobial use, including treatment duration, can mitigate AMR emergence. This is particularly critical in candidemia, a severe condition with a 45% crude mortality rate, as the 14-day minimum treatment period has not been challenged in randomised comparison. A comprehensive literature search was conducted in August 2023, revealing seven original articles and two case series discussing treatment durations of less than 14 days for candidemia. No interventional trials or prospective observational studies assessing shorter durations were found. Historical studies showed varying candidemia treatment durations, questioning the current 14-day minimum recommendation. Recent research observed no significant survival differences between patients receiving shorter or longer treatment, emphasising the need for evidence-based guidance. Treatment duration reduction post-blood culture clearance could decrease exposure to antifungal drugs, limiting selection pressure, especially in the context of emerging multiresistant Candida species. Candidemia's complexity, emerging resistance and potential for shorter in-hospital stays underscore the urgency of refining treatment strategies. Evidence-driven candidemia treatment durations are imperative to balance efficacy with resistance prevention and ensure the longevity of antifungal therapies. Further research and clinical trials are needed to establish evidence-based guidelines for candidemia treatment duration.

Pluronic F-127 Enhances the Antifungal Activity of Fluconazole against Resistant Candida Strains.

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance.