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Invasive candidiasis (IC) is an increasingly prevalent, costly, and potentially fatal infection brought on by the opportunistic yeast, Candida. Previously, IC has predominantly been caused by C. albicans which is often drug susceptible. There has been a global trend towards decreasing rates of infection secondary to C. albicans and a rise in non-albicans species with a corresponding increase in drug resistance creating treatment challenges. With advances in management of malignancies, there has also been an increase in the population at risk from IC along with a corresponding increase in incidence of breakthrough IC infections. Additionally, the emergence of C. auris creates many challenges in management and prevention due to drug resistance and the organism's ability to transmit rapidly in the healthcare setting. While the development of novel antifungals is encouraging for future management, understanding the changing epidemiology of IC is a vital step in future management and prevention.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [-13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [-16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [-0.2%, 40.2%]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

UNLABELLED: Candida auris is a multidrug-resistant fungal pathogen with a propensity to colonize humans and persist on environmental surfaces. C. auris invasive fungal disease is being increasingly identified in acute and long-term care settings. We have developed a prototype cartridge-based C. auris surveillance assay (CaurisSurV cartridge; research use only) that includes integrated sample processing and nucleic acid amplification to detect C. auris from surveillance skin swabs in the GeneXpert instrument and is designed for point-of-care use. The assay limit of detection (LoD) in the skin swab matrix was 10.5 and 14.8 CFU/mL for non-aggregative (AR0388) and aggregative (AR0382) strains of C. auris, respectively. All five known clades of C. auris were detected at 2-3-5× (31.5-52.5 CFU/mL) the LoD. The assay was validated using a total of 85 clinical swab samples banked at two different institutions (University of California Los Angeles, CA and Wadsworth Center, NY). Compared to culture, sensitivity was 96.8% (30/31) and 100% (10/10) in the UCLA and Wadsworth cohorts, respectively, providing a combined sensitivity of 97.5% (40/41), and compared to PCR, the combined sensitivity was 92% (46/50). Specificity was 100% with both clinical (C. auris negative matrix, N = 31) and analytical (non-C. auris strains, N = 32) samples. An additional blinded study with N = 60 samples from Wadsworth Center, NY yielded 97% (29/30) sensitivity and 100% (28/28) specificity. We have developed a completely integrated, sensitive, specific, and 58-min prototype test, which can be used for routine surveillance of C. auris and might help prevent colonization and outbreaks in acute and chronic healthcare settings. IMPORTANCE: This study has the potential to offer a better solution to healthcare providers at hospitals and long-term care facilities in their ongoing efforts for effective and timely control of Candida auris infection and hence quicker response for any potential future outbreaks.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

The fungal Bromodomain and Extra‐Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on‐target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4. On‐target antifungal activity is established by devising two yeast‐based inhibition assays: a growth assay using humanized Candida strains in which the Bdf1 BDs are replaced by their Brd4 counterparts, and a NanoBiT assay that evaluates the BD‐mediated association of Bdf1 with chromatin. These assays additionally enable the discovery that BET inhibitor I‐BET726 targets both Bdf1 BDs, inhibits the growth of a broad spectrum of Candida species, including antifungal‐resistant clinical isolates, and displays efficacy in an invertebrate animal model of infection. These collective findings highlight the promising potential of Bdf1 BD inhibitors as an innovative class of antifungal therapeutics and the pivotal role of yeast‐based assay development toward achieving this end. [ABSTRACT FROM AUTHOR]

Candida spp. are opportunistic pathogens associated with mucosal and cutaneous infections. Its increased resistance to antifungals has instigated the development of adjunct treatments, such as antimicrobial photodynamic therapy (aPDT). This study evaluated the antifungal effects of aPDT mediated by two tetra-cationic porphyrins with peripheral platinum(II) complexes (3-Pt and 4-Pt). A thorough investigation was performed using in vitro and in vivo assays to determine their antifungal activity on Candida albicans and toxicity in human cells. Next, specific models were employed to search for understanding of the action of aPDT on Candida-associated infections. As a result, a MIC value of 16 μmol/L was found for both porphyrins, with low toxicity to keratinocytes even in higher concentrations. Planktonic cultures of C. albicans treated by aPDT with 3-Pt achieved complete inhibition in 40 s, while 4-Pt reduced 1.3 Log10 (CFU) within 80 s. These effects were also extended to C. albicans biofilms, in which 3-Pt and 4-Pt reduced 4 and 0.8 Log10 (CFU), respectively. The mechanisms of action of 3-Pt were related to hyphae inhibition, increased ROS production, and cell wall damage. Finally, 3-Pt showed efficacy against denture stomatitis biofilms in a microcosm model and burn wounds in Galleria mellonella, indicating its potential for treating Candida-associated infections. [ABSTRACT FROM AUTHOR]

Candiduria is a condition in which Candida species are found in the urine. Candiduria is commonly found in hospitalized patients, especially those with diabetes mellitus and those receiving medical care, especially using urine catheters. Although Candida is a normal part of the body's flora, certain species can opportunistically cause urinary tract infections (UTIs). This study aimed to analyze the risk factors for Candida UTIs in patients hospitalized at Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. This was an analytical, observational, and cross-sectional study included 52 patients hospitalized with Candida culture results, who underwent urine re-collection for confirmatory culture examination. The results showed a significant correlation between candiduria (p = 0.000); yeast, pseudohyphae, or hyphae found on Gram staining (p = 0.024); and previous antibiotic use (p = 0.027) with Candida UTIs. This suggests that candiduria, presence of yeast, pseudohyphae, or hyphae found on Gram staining, and previous antibiotic use are risk factors for Candida UTIs. In conclusion, these findings underscore the need for careful monitoring of antibiotic use and candiduria in hospitalized patients to prevent Candida UTIs. [ABSTRACT FROM AUTHOR]

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Background: Many risk factors, including COVID-19 infection, lead to the development of invasive Candida infection in intensive care unit patients. The aim of this study was to evaluate the risk factors affecting mortality along with the clinical characteristics of candidemia patients. Methods: This retrospective study was conducted among patients hospitalized at the Anesthesiology and Reanimation Clinic between June 2020 and December 2021. The clinical and laboratory characteristics of 165 patients with candidemia were recorded. The difference between patients with and without COVID-19 infection was evaluated statistically. Multivariate analysis was performed to determine factors affecting mortality. Results: A total of 165 patients were included in the study, 52.1% of whom were male. The mean age of the patients was 66.5 (median 18–97) years. The percentage of patients with COVID-19 infection was 70.9%. The mean leukocyte count and aspartate transaminase, alanine transaminase, C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer levels were significantly greater in COVID-19 patients than non COVID-19 patients (p < 0.05). The mortality rate in patients with candidemia was 80.2%. The presence of comorbidities, corticosteroid use, advanced age, and high ferritin and D-dimer levels negatively affected mortality, according to the multivariate analysis results. C. albicans was the most frequently isolated Candida species. Conclusions: We detected higher mortality rates in patients with candidemia who were elderly, had comorbidities, received corticosteroid treatment and had elevated ferritin and D-dimer levels. When steroids are used, it is necessary to remember that this drug is a double-edged sword and to be careful of fungal infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: Continuous monitoring blood culture systems (CMBCSs) are revolutionary automated instruments that facilitate the rapid identification of pathogens in blood samples from patients with sepsis. However, with only a few CMBCSs being widely used as references, user dependency on these limited options has grown. In response, a new CMBCS was developed and compared with existing systems to evaluate microbial growth. Methods: HubCentra84 was compared to BacT/Alert® 3D and BACTEC™ FX. Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Bacteroides fragilis, and Candida albicans were selected as representative clinically infectious microorganisms. Colonies from pure cultures were diluted with 0.9% saline to create simulated sepsis specimens (SSSs). The SSSs were injected into dedicated culture bottles for each instrument. Thirty paired tests were performed for each strain. Results: Colony-forming units of the added SSSs were consistent according to bacteria, and all strains demonstrated robust growth in three CMBCSs. Time-to-positivity was uniformly observed according to the instruments used. The novel CMBCS detected the growth of the clinically significant bacteria S. aureus, S. pneumoniae, E. coli, and P. aeruginosa approximately 2 h faster than the other two systems. However, it was approximately 200 min slower for C. albicans and 3000 min for B. fragilis. Conclusions: The novel CMBCS demonstrates advantages in detecting the growth of common clinical bacteria. Although slow growth was detected for certain microorganisms, it successfully captured the growth of all tested microorganisms. [ABSTRACT FROM AUTHOR]

Diplopterys pubipetala (Malpighiaceae) is a liana native to the Brazilian Cerrado biome, traditionally used in Ayahuasca preparations. Despite its cultural importance, research on its chemical composition and biological activities, which may have therapeutic potential, is limited. This study investigated the volatile and non-volatile secondary metabolites of D. pubipetala leaves, their antioxidant capacity, and their antibacterial and antifungal activities. Volatile compounds were identified using gas chromatography-mass spectrometry (GC-MS) coupled to solid-phase microextraction (SPME), while non-volatile compounds were annotated using UHPLC-MS/MS-ESI-Q-TOF. Antioxidant capacity was evaluated by DPPH assay, and antimicrobial activity was assessed in vitro against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida species (C. albicans, C. tropicalis, C. glabrata). GC-MS analysis revealed 25 predominant volatile compounds, including ethyl dodecanoate, ethyl tetradecanoate, nonanoic acid, and 5-methylhexan-2-one, with documented antifungal, antioxidant, and antimicrobial activities. The crude extract and ethyl acetate fraction showed strong antioxidant capacity (EC50 9.83 µg/mL and 6.42 µg/mL, respectively), and antifungal effects were observed against Candida species. This study provides the first comprehensive investigation of the antioxidant capacity and antibacterial and antifungal activities of D. pubipetala, together with a detailed chemical profile of its volatile compounds. [ABSTRACT FROM AUTHOR]

Carbon dioxide is a signaling cue critical for fungal pathogenesis. Ptc2, a type 2C protein phosphatase (PP2C), serves as a conserved CO2 sensor in fungi. By combining phosphoproteomic and biochemical assays, we identified Hsp90 as a direct target of Ptc2 at host CO2 concentrations and Ssb1 as a Ptc2 target protein regardless of CO2 levels in Candida albicans, the most prevalent human fungal pathogen. Ptc2 forms reversible condensates at elevated CO2, which enables the recruitment of Hsp90, but not Ssb1, to condensates, allowing efficient dephosphorylation. This process confers an enhanced susceptibility to caspofungin in vitro and during in vivo infection therapy. Importantly, we demonstrate this phenomenon in non-albicans Candida species. Sequential passages of C. albicans in mice with caspofungin treatment readily induce in vivo drug tolerance, causing therapeutic failure. These evolved strains display increased resistance to caspofungin under host concentrations of CO2 but remain susceptible in air. Collectively, our study reveals a profound impact of host concentrations of CO2 on antifungal drug susceptibility and connects this phenotype to therapeutic outcomes and highlights condensate formation as an efficient means that enables selective recruitment of substrates for certain signaling events. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionWe sought to re-evaluate the utility of inpatient ocular Candidiasis screening, subsequent interventions, and outcomes, to ultimately guide alignment between American Academy of Ophthalmology (AAO) and Infectious Diseases Society of America (IDSA) guidelines.A retrospective cohort study was conducted from 2017–2024 at two tertiary care centers in the New York metropolitan area. Inclusion criteria included positive Candidal cultures, a pertinent International Classification of Diseases, 10th revision (ICD-10) code, or both. Culture results, mental status, visual acuity, ocular symptoms, systemic antifungal use, dilated fundus exam (DFE) findings, immunocompromised status, and interventions performed were recorded.Of 897 patient encounters meeting inclusion criteria, 285 (31.8%) underwent consultation to rule-out ocular Candidiasis. Among these patients, 212 (74.4%) had an unremarkable DFE, 35 (12.3%) had DFE findings attributable to other comorbidities, 24 (8.4%) had nonspecific DFE findings requiring follow-up, nine (3.2%) were diagnosed with Candida retinitis, and one (0.4%) had Candida endophthalmitis. There were no statistically significant differences in the odds of DFE positivity between the immunocompromised versus immunocompetent group (χ2 = 0.881, p = 0.348) or the symptomatic versus asymptomatic group (χ2 = 0.297, p = 0.586). During the entire study period, no ophthalmology-directed interventions were made.Candida endophthalmitis and Candida retinitis are rare in the inpatient setting, even in patients with confirmed Candidemia. Patients are universally started on empiric intravenous antifungal treatment by primary or infectious disease teams prior to ophthalmology consultation, limiting the yield of these examinations. Further studies should be undertaken to create a protocol for these patients such that serious sequelae of disease are prevented while resources are also utilized appropriately. [ABSTRACT FROM AUTHOR]

Background: Amphotericin is admixed to Polymethylmethacrylic (PMMA) spacers for fungal periprosthetic joint infections (PJI) during two-stage exchanges. We aimed to analyse the mechanical properties of PMMA cement with admixed Amphotericin B. Materials and methods: We tested Amphotericin in PMMA cement mechanically, its elution properties in vitro and present two cases of fungal PJI treated with Amphotericin B powder in Copal cement in vivo. Results: Sterile Amphotericin B is not available as a pure substance but only as powder for infusions. PMMA mixed with such pharmaceutical Amphotericin B formulations colored the cement orange. Compression strength was slightly decreased, bending and impact strength significantly decreased whereas bending modulus was increased. Drug elution was high within the first 24 h and decreased over time until day 5. Amphotericin B in combination with Copal was successfully used in two cases with Candida ssp. infections. No negative side effects, especially no nephrotoxic effects, were observed. Sterile Amphotericin B powder for preparing an infusion solution contains only small amounts of pure drug. In vivo polymicrobial Candida-infections with bacterial co-infection were successfully treated using the combination of Copal cements with added Amphotericin B without systemic nephrotoxic impact. Conclusions: The addition of Amphotericin B to PMMA cement affects the cement's properties in vitro whereas in vivo the combination with Copal is clinically successful in treating complex cases of fungal PJI. Level of evidence: Level IV. [ABSTRACT FROM AUTHOR]

Patients with liver disease in the intensive care unit (ICU) face a unique susceptibility to infection due to the complex immune dysfunction resulting from hepatic failure. Bacterial infections are commonly present in these patients upon arrival to the hospital, often being the primary reason for ICU admission. In contrast, invasive fungal infections (IFIs) afflict a smaller percentage of patients and are usually discovered in the course of the ICU stay. IFI diagnosis in the ICU, particularly in patients with liver disease, is often delayed or overlooked, contributing to the extremely high ICU mortality associated with IFI in these patients despite the availability of effective (and largely safe) antifungal therapy. Thus, to improve outcomes, it is crucial for intensive care clinicians to be vigilant for IFIs in patients with liver disease. This review aims to contribute to the intensive care literature in this regard. We begin with an overview of normal antifungal immunity followed by a summary of how it may become compromised in the setting of hepatic dysfunction. Next, a general discussion of IFIs in liver disease is presented and then the three most relevant fungal pathogens, namely Candida, Aspergillus, and Cryptococcus, are individually examined. This review concludes by highlighting key knowledge and practice gaps that require attention by the scientific and clinical communities in the coming years. [ABSTRACT FROM AUTHOR]

There is an increasing interest in yeasts isolated from natural sources to be used as probiotics. Saccharomyces-based probiotics have been proposed as a valid alternative to the conventional drug therapy for the prevention and treatment of vulvovaginal candidiasis, also considering the resistance of some Candida strains to many antifungals. Here, we isolated from an artisanal sourdough a new yeast strain which was identified as Kluyveromyces marxianus and assessed its probiotic and safety properties, which resulted in comparable properties to all those exhibited by the commercial probiotic Saccharomyces boulardii. Then, we checked the antagonistic activity of the new isolate against some clinical fluconazole resistant C. albicans strains, showing its ability to inhibit filamentation, biofilm formation, and the adhesion of C. albicans to vaginal epithelial A-431 cells. Also, K. marxianus reduced the cell damage provoked by C. albicans and the expression of SAP2 and SAP6 genes. On the whole, our results enlarge the spectrum of the beneficial properties of the food-grade yeast K. marxianus showing for the first time its biotherapeutic potential against C. albicans. [ABSTRACT FROM AUTHOR]

Invasive candidiasis is a common fungal infection associated with multiple risk factors, such as cancer, neutropenia, corticosteroid therapy, catheterization, and the use of broad-spectrum antibiotic treatment. Candida albicans is the predominant causative agent, although other Candida species have been emerging in the last years, together with a rise in a number of strains resistant to the currently available antifungal drugs, which poses a challenge when treating these infections. Drug repurposing and drug combinations are promising strategies for the treatment of invasive mycoses. In this study, we evaluated the effect of the combination of fluconazole (FLZ) and cyclosporine A (CsA) against 39 clinical isolates and reference strains of Candida. Two methods, the Loewe additivity model and Bliss independence model, were used to assess the antifungal activity of the drug combination according to CLSI and EUCAST guidelines. The results demonstrated a synergistic effect between fluconazole (FLZ) and cyclosporine A (CsA) against 15–17 Candida isolates, depending on the evaluation model used, including FLZ-resistant strains of C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. Notably, the combination significantly reduced the minimum inhibitory concentration (MIC) of FLZ in a substantial number of isolates, including those with resistance to FLZ. Additionally, time–kill curve studies confirmed the synergistic interaction, further validating the potential of this combination as an alternative therapeutic strategy for candidiasis treatment. These findings emphasize the importance of investigating innovative drug combinations to address the challenges posed by antifungal resistance and improve treatment options for invasive fungal infections. [ABSTRACT FROM AUTHOR]

Intra-abdominal candidiasis (IAC) is associated with significant diagnostic and therapeutic challenges in critically ill patients. Traditional fungal cultures are slow, delaying appropriate antifungal treatment. (1,3)-β-D-glucan (BDG), a component of the fungal cell wall, has emerged as a potential biomarker for IAC, but its use in ICU settings is complicated by frequent false-positives results from invasive procedures and underlying conditions. This review examines the diagnostic value of BDG when present in serum and peritoneal fluid. While serum BDG is effective for excluding invasive fungal infections like candidemia, its specificity for IAC remains low in critically ill patients. Recent studies suggest that BDG levels in peritoneal fluid may provide better diagnostic accuracy, distinguishing IAC from bacterial peritonitis with higher specificity. We discuss the advantages, limitations, and practical aspects of BDG testing, emphasizing the potential of peritoneal BDG as a complementary tool. Further research is needed to refine diagnostic thresholds, validate its clinical utility, and establish the role of peritoneal BDG in improving timely, targeted antifungal treatment for IAC. [ABSTRACT FROM AUTHOR]

Candida infections are a global health concern, increasingly complicated by rising antimicrobial resistance (AMR). This study analyzed the prevalence and AMR patterns of circulating Candida species in Amman, Jordan, using electronic records from a tertiary teaching hospital's microbiology lab (from 2017 to 2022). Complete records of Candida isolates (n = 2673) were assessed by sample type, species, and AMR. Among positive blood samples, C. albicans accounted for the majority (38.7%), followed by C. tropicalis (19.0%), C. parapsilosis (18.3%), Nakaseomyces glabratus (14.6%), and Pichia kudriavzevii (9.5%). Non-albicans species demonstrated higher resistance to Caspofungin, notably P. kudriavzevii (23.1%), N. glabratus (30.0%), and C. parapsilosis (32.0%), compared to C. albicans (1.9%). In high vaginal swabs, C. albicans was most prevalent (63.7%), with N. glabratus also notable (28.6%); Fluconazole resistance in C. albicans remained low (2.0%). Across all pooled isolates, AMR was similar between inpatients and outpatients, except for Micafungin, where inpatient resistance was significantly higher. In conclusion, non-albicans species predominated in blood infections and demonstrated pronounced AMR. Micafungin resistance was notably higher among inpatients. Variations in Candida species and AMR by sample type suggest that aggregating samples in registry studies may obscure critical patterns. [ABSTRACT FROM AUTHOR]

Background Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. Methods This was a retrospective observational multinational study including patients diagnosed with Candida -related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. Results A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0–79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5–181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079–3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157–3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI:.305–.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P =.008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P =.003), but there was no difference comparing 1- to 2-stage exchanges (P =.777). Conclusions Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Two new triterpenoid saponins, namely camsinsaponins A and B (1, 2), along with two known congeners (3, 4) were isolated from Camellia sinensis flowers. Their structures were determined by extensive spectroscopic data. All compounds were assessed for antifungal bioactivity against Candida albicans, Candida glabrata, and Candida tropicalis. Compounds 1–4 showed excellent inhibitory effects. Notably, in regard to compounds 1 and 2, their MIC values against C. albicans were close to those of the positive control, fluconazole. Furthermore, the inhibitory elements of compounds 1–4 on C. glabrata were better than those of fluconazole. The aforementioned findings offer valuable insights for future development of novel therapeutic strategies against drug-resistant infections. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent Vulvovaginal Candidiasis (RVVC) is a problematic clinical condition for which fluconazole treatment is commonly prescribed. This study investigated the interkingdom vaginal and gastrointestinal microbiomes of RVVC patients who use fluconazole intermittently or as longer-term maintenance therapy for symptom management and compared them to healthy controls. Methods: Vaginal swabs and fecal samples were collected. A novel interkingdom analysis was performed using 16 S rRNA and ITS1 gene sequencing to compare the diversity and taxonomic composition of vaginal microbiome (VMB) and gastrointestinal microbiome (GIMB). Results: Twenty-seven women participated: 10 intermittent users and healthy controls and 7 maintenance therapy. The study revealed that microbiomes of fluconazole users do not differ in diversity metrics from healthy controls. RVVC patients using intermittent fluconazole displayed a higher abundance of vaginal C. albicans than healthy controls. Candida species pairings were not commonly observed between sites in individuals and, as such a fecal reservoir is unlikely to be implicated in recurrent symptomatology. In many of the RVVC non-Candida fungal spp. were identified in the vaginal microbiome. Users of fluconazole displayed elevations of the CST-I (Community State Type 1) associated bacterium L. crispatus. All participants displaying vaginal Candida spp. belonged to either bacterial CST-I or CST-III (Community State Type 3- L. iners associated). Conclusion: To our knowledge, this is the first study to compare the interkingdom VMB-GIMB of women with RVVC using oral fluconazole. As fluconazole users in this study represent a typical RVVC population, trends observed in microbial abundance require further analysis to establish fluconazole's long-term microbiome safety. Examining the microbiome at both sites adds to the current understanding of microbial associated with the condition. [ABSTRACT FROM AUTHOR]

Introduction: The epidemiology of candidemia has shifted in the past few decades; drug-resistant non-albicans Candida species have become more prevalent worldwide. The aim of this retrospective study was to determine the epidemiology of Candida species isolated from hospitalized neonates, children and adults, and to investigate a potential changing susceptibility pattern in a large general tertiary hospital. Methods: All unique Candida strains isolated from candidemia cases between 1 January 2020 and 15 October 2024 were identified, and their susceptibility profile was characterized. The distribution pattern in different ward types (medical, surgical, pediatric and ICU) was recorded. Cumulative annual susceptibility profiles were compared. Results: Candidemia incidence increased during the COVID-19 pandemic, from 0.63/1000 patient-days in 2020 to 0.96/1000 patient-days in 2022, and has since slightly decreased (0.83 and 0.89 in 2023 and 2024, respectively). Candidemia-associated mortality was high (>50%) in 2020 and peaked during the pandemic. During the study period, Candida parapsilosis remained the most frequent Candida spp. However, since the first isolation of Candida auris from the bloodstream in late 2022, and despite intense infection control measures taken, its frequency sharply climbed to the second position after only C. parapsilosis in the first 10 months of 2024 (33.6% vs. 25.2% for C. parapsilosis and 21.0% for C. albicans). While C. albicans has remained highly susceptible to fluconazole (1% resistance rate), C. parapsilosis manifested significant resistance to fluconazole during 2022–2024 (52%). C. auris was universally resistant to azoles and one isolate also resistant to echinocandins. Conclusions: A high prevalence of azole resistance of C. parapsilosis, the most frequently isolated Candida species, persists, and a significant rise of C. auris was recorded in nosocomial bloodstream infections with severe implications on public health. [ABSTRACT FROM AUTHOR]

Background/Objectives: Ulcerative colitis (UC) and Crohn's disease (CD) are the usual clinical forms of inflammatory bowel disease (IBD). Changes in the oral microbiota, especially the presence of emerging fungi and herpesviruses, have been shown to worsen the clinical aspects of IBD. The aim of this study was to screen for emerging pathogens in the oral yeast microbiota and the presence of herpesvirus in IBD patients. Methods: Oral swabs of seven UC or CD patients were collected. The samples were plated on Sabouraud Dextrose Agar and subcultured on CHROMagar Candida and CHROMagar Candida Plus. Polyphasic taxonomy was applied and identified using molecular tools, such as MALDI-TOF MS and ITS partial sequencing. Multiplex qPCR was used to identify the herpesvirus. Results: The mean age was 38.67 ± 14.06 years, 57.14% were female, and two had diabetes. The CD patients presented with Rhodotorula mucilaginosa, Candida orthopsilosis and Kodamaea jinghongensis, while the UC patients presented with Cutaneotrichosporon dermatis, Candida glabrata, Candida lusitanea and Candida tropicalis. Two UC individuals had at least one herpesvirus. In the first individual, a co-detection of Herpes Simplex Virus 1 (HSV-1) and C. lusitaniae was observed. The second presented with co-infections of Epstein–Barr virus (EBV), Human Herpesvirus 7 (HHV-7) and C. tropicalis. Conclusions: We identified rarely described yeasts and co-infections in IBD patients, highlighting the need to identify emerging pathogens in the oral microbiota, as they may contribute to opportunistic infections. [ABSTRACT FROM AUTHOR]

The oral cavity is known to harbor hundreds of microorganisms, belonging to various genera, constituting a peculiar flora called the oral microbiome. The change in the relative distribution of the constituents of this microbial flora, due to any reason, leads to oral dysbiosis. For centuries, oral dysbiosis has been linked to the etiopathogenesis of several medical illnesses, both locally and systemically-. However, aided by the recent advent of bio-technological capabilities, several reports have re-emerged that link oral dysbiosis to oral carcinogenesis, and numerous studies are currently exploring their association and plausible mechanisms. Some of the proposed mechanisms of oral dysbiosis-induced carcinogenesis (ODIC) include—a bacteria-induced chronic inflammatory state leading to direct cellular damage, inflammatory-cytokine-mediated promotion of cellular proliferation and invasion, release of bacterial products that are carcinogenic, and suppression of local immunity by alteration of the tumor microenvironment. However, the actual interactions between these cellular mechanisms and their role in carcinogenesis are not yet fully understood. This review provides a comprehensive overview of the various hypotheses and mechanisms implicated in the ODIC, along with the corresponding molecular aberrations. Apart from discussing the usual constituents of the oral microbiome profile, the review also summarizes the various dysbiosis profiles implicated in ODIC. The review also sheds light on the potential clinical implications of the research on oral microbiome in the prevention and management of oral cancer. [ABSTRACT FROM AUTHOR]

Background: Proliferative Verrucous Leukoplakia (PVL) presents a unique manifestation of Oral Leukoplakia, characterized by its notable propensity for rapid advancement, dynamic clinical and histopathological alterations, and heightened risk of malignant transformation. Aim: The present systematic review explores the demographic characteristics, risk factors, progression patterns, treatment preferences, and outcomes for PVL lesions that undergo malignant transformation. Materials and methods: An electronic search was executed across various databases, such as PubMed, Scopus, Science Direct, Web of Science and Wiley Online Library from 1985 to December 2023, focusing on studies of PVL malignant transformation. Data on demographics, clinical features, treatment, and outcome data were synthesized, with bias assessed using Joanna Briggs Institute Criteria and outcomes evaluated using Comprehensive Meta-Analysis version (CMA) 3.0 software. Results: Among 998 articles, 53 met inclusion criteria, covering 1159 PVL patients, with 48.4% experiencing malignant transformation over an average 6.28 ± 3.73—year follow-up. Most cases had low or moderate bias risk. In the malignant group, females comprised 74.3% of cases, with a mean age of 66.23 ± 7.76 years and had a 1.96 times greater risk of developing cancer (OR 1.96, 95% CI 1.38—2.782; p = 0.001). Gingiva (20%) and gingiva/buccal mucosa (17.4%) were commonly affected. Tobacco and alcohol showed weak associations, with most patients being non-smokers (59.54%) and non-drinkers (78.18%). HPV and candida infection positivity were tested in only a few studies and noted in a limited number of cases (33.3% and 38.46%, respectively). Malignant transformation mainly was invasive carcinoma (86.8%). Surgery was the primary treatment (58.33%), with 55.56% recurrence in 162 cases of data availability on recurrence. Of 228 patients with data availability, 33.77% succumbed to oral cancer from PVL-related oral cancer. Conclusions: PVL, a rare variant of leukoplakia, poses a significant risk of cancer, emphasizing the need for vigilant monitoring and proactive treatment. It mainly affects elderly females without typical cancer risk factors. Understanding its etiology could aid early detection and management. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical relevance, origin, transmission, and resistance of Candida auris (C. auris) isolates from two outbreaks and sporadic occurrences from one hospital in China. Methods: A total of 135 C. auris isolates were collected. Clinical characteristics were obtained and antifungal susceptibility testing (AFST) was performed using the method of broth microdilution. Phylogenetic tree, WGS analysis, and single nucleotide polymorphisms (SNPs) were used to determine the origin, transmission, and resistance mechanisms. Results: A total of 31 patients (91.2%, 31/34) received invasive medical procedures and 13 patients (38.2%, 13/34) had antifungal agents before C. auris infection/colonization, except one patient whose clinical information was missing. Only 4 cases of C. auris candidemia were observed. 18 patients died, 13 patients recovered, and the outcomes of 3 patients were not available. A total of 35 C. auris isolates, which were successfully cultivated and the first isolated or harbored specific drug-resistant phenotype from each patient, were selected to be sequenced and further analyzed. C. auris isolates presented low genetic variability and belonged to clade I, possibly originating from BJ004-H7 in Beijing. All 35 isolates were resistant to Fluconazole (FCZ) and amphotericin B (AMB), and 3 isolates were resistant to caspofungin (CAS). Mutations in ERG11 and FKS1 were linked to reduced azole and echinocandin susceptibility, respectively. Conclusions: Two outbreaks of highly clonal, multidrug-resistant C. auris isolates within the medical facility were reported. The intensive performance of disinfection measures helped block in-hospital transmission. Understanding the epidemiology, drug resistance and management of C. auris will be helpful for implementing effective infection control and treatment strategies. Highlight: Two outbreaks and sporadic occurrences of C. auris from one hospital in China. Multidrug-resistant C. auris to ≥ 3 drug class (azole, amphotericin B, and echinocandin) was reported. Intensive performance of disinfection measures helped block in-hospital transmission of C. auris. [ABSTRACT FROM AUTHOR]