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This clinical case is about a 50-year old woman, a refugee from Ukraine, without known epidemiological risk factors, with newly diagnosed human immunodeficiency virus-1 (HIV-1) infection in acquired immune deficiency syndrome (AIDS) stage. Qesophageal candidiasis as an indicator disease of HIV in this case was the first diagnosis that promoted further investigation, revealing both primary HIV infection and sequentially other opportunistic infections — cytomegalovirus, Epstein Barr virus, and miliary tuberculosis. Oesophageal candidiasis was visualised by the oesophagogastroduodenoscopy method, which was initially performed due to detected anaemia to rule out bleeding from the gastrointestinal tract. Deep immunosuppression was provided to this patient and this led to the development of miliary tuberculosis, worsening the prognosis. The patient was prescribed treatment for several opportunistic infections, also anti tuberculosis treatment, as well as combined antiretroviral treatment, which stabilised the situation. In this case our patient developed odynophagia and dysphagia, common complications of oesophageal candidiasis, so she had to receive nutrition through a nasogastric tube. [ABSTRACT FROM AUTHOR]

Early identification of human pathogens is crucial for the effective treatment of bloodstream infections to prevent sepsis. Since pathogens that are present in small numbers are usually difficult to detect directly, we hypothesize that the behavior of the immune cells that are present in large numbers may provide indirect evidence about the causative pathogen of the infection. We previously applied time-lapse microscopy to observe that neutrophils isolated from human whole-blood samples, which had been infected with the human-pathogenic fungus Candida albicans or C. glabrata, indeed exhibited a characteristic morphodynamic behavior. Tracking the neutrophil movement and shape dynamics over time, combined with machine learning approach, the accuracy for the differentiation between the two Candida species was about 75%. In this study, the focus is on improving the classification accuracy of the Candida species using advanced deep learning methods. We implemented (i) gated recurrent unit (GRU) networks and transformer-based networks for video data, and (ii) convolutional neural networks (CNNs) for individual frames of the time-lapse microscopy data. While the GRU and transformer-based approaches yielded promising results with 96% and 100% accuracy, respectively, the classification based on videos proved to be very time-consuming and required several hours. In contrast, the CNN model for individual microscopy frames yielded results within minutes, and, utilizing a majority-vote technique, achieved 100% accuracy both in identifying the pathogen-free blood samples and in distinguishing between the Candida species. The applied CNN demonstrates the potential for automatically differentiating bloodstream Candida infections with high accuracy and efficiency. We further analysed the results of the CNN using explainable artificial intelligence (XAI) techniques to understand the critical features and patterns, thereby shedding light on potential key morphodynamic characteristics of neutrophils in response to different Candida species. This approach could provide new insights into host-pathogen interactions and may facilitate the development of rapid, automated diagnostic tools for differentiating fungal species in blood samples.

Cetaceans, which are crucial in marine ecosystems, act as sentinels for ecosystem and human–environmental health. However, emerging fungal infections, particularly by Candida spp., pose a growing concern in these marine mammals. This review consolidates current knowledge on the prevalence, clinical manifestations, species distribution, and antifungal resistance of Candida infections in cetaceans. We detail the diverse pathogenic impacts of Candida, including respiratory, dermal, and systemic afflictions, underscoring diagnostic and treatment challenges amid rising antifungal resistance. Our analysis extends beyond health concerns in captive cetaceans, where confinement stress heightens vulnerability, to encompass substantial ecological risks in wild populations. The review emphasizes the One Health perspective, linking cetacean health with broader environmental and human public health issues. We particularly focus on the potential zoonotic transmission of emerging fungal pathogens such as Candida auris and the role of environmental changes in fostering antifungal resistance. The study underscores the need for concerted, interdisciplinary efforts in veterinary, medical, and environmental sciences to enhance understanding and management of Candida infections in cetaceans. We advocate for comprehensive monitoring and collaborative research initiatives to mitigate the rising challenge of these infections. Addressing Candida spp. in cetaceans is not just a conservation priority but a critical step in safeguarding overall marine health and, by extension, human health in the context of evolving infectious diseases. [ABSTRACT FROM AUTHOR]

Over 21 months, 12 patients with invasive Candida infections detected during the course of treatment of bacterial endocarditis, including 11 with candidemia, were identified. Invasive Candida infections can occur as a complication of bacterial endocarditis and may occur more frequently in patients with injection drug use and broad-spectrum antibiotic exposure. [ABSTRACT FROM AUTHOR]

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen. [ABSTRACT FROM AUTHOR]

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.

The prevalence of edentulism in India has been on a rise in the recent years. Complete dentures are the most common treatment modality for restoration of lost teeth. Failure to adhere to maintenance of denture hygiene is associated with a lot of problems. Mechanical and chemical methods are the two basic methods of maintenance of denture hygiene. Although scientific literature has failed to establish superiority of any method over other, we suggest adhering to concomitant use of mechanical and chemical cleaning methods for obtaining optimal reduction of denture biofilm. Besides this, patient education and communicating evidence-based guidelines for maintenance of denture hygiene need to be adhered to and communicated to patient as well. [ABSTRACT FROM AUTHOR]

Candida auris infections are difficult to treat due to acquired drug resistance against one or multiple antifungal drug classes. The most prominent resistance mechanisms in C. auris are overexpression and point mutations in Erg11, and the overexpression of efflux pump genes CDR1 and MDR1. We report the establishment of a novel platform for molecular analysis and drug screening based on acquired azole-resistance mechanisms found in C. auris. Constitutive functional overexpression of wild-type C. auris Erg11, Erg11 with amino acid substitutions Y132F or K143R and the recombinant efflux pumps Cdr1 and Mdr1 has been achieved in Saccharomyces cerevisiae. Phenotypes were evaluated for standard azoles and the tetrazole VT-1161. Overexpression of CauErg11 Y132F, CauErg11 K143R, and CauMdr1 conferred resistance exclusively to the short-tailed azoles Fluconazole and Voriconazole. Strains overexpressing the Cdr1 protein were pan-azole resistant. While CauErg11 Y132F increased VT-1161 resistance, K143R had no impact. Type II binding spectra showed tight azole binding to the affinity-purified recombinant CauErg11 protein. The Nile Red assay confirmed the efflux functions of CauMdr1 and CauCdr1, which were specifically inhibited by MCC1189 and Beauvericin, respectively. CauCdr1 exhibited ATPase activity that was inhibited by Oligomycin. The S. cerevisiae overexpression platform enables evaluation of the interaction of existing and novel azole drugs with their primary target CauErg11 and their susceptibility to drug efflux. [ABSTRACT FROM AUTHOR]

Arome Solomon Odiba,1,2 Olanrewaju Ayodeji Durojaye,3– 5 Ifeoma Maureen Ezeonu,6 Anthony Christian Mgbeahuruike,7 Bennett Chima Nwanguma1,2 1Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria; 2Department of Molecular Genetics and Biotechnology, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria; 3Department of Chemical Sciences, Coal City University, Emene, Enugu State, Nigeria; 4Department of Molecular and Cell Biology, University of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of China; 5MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 6Department of Microbiology, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria; 7Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, 410001, NigeriaCorrespondence: Bennett Chima Nwanguma; Anthony Christian Mgbeahuruike, Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Enugu State, Nsukka, 410001, Nigeria, Tel +234 8063655062, Email bennett.nwanguma@unn.edu.ng; anthony.mgbeahuruike@unn.edu.ngBackground: Resistance to antifungal drugs for treating Candida infections remains a major concern globally despite the range of medications available. Most of these drugs target key proteins essential to the life cycle of the organism. An enzyme essential for fungal cell membrane integrity, lanosterol 14–α demethylase (CYP51), is encoded by the ERG11 gene in Candida species. This enzyme is the target of azole–based drugs. The organism has, however, devised molecular adaptations to evade the activity of these drugs.Materials and Methods: Classical methods were employed to characterize clinical isolates sampled from women and dogs of reproductive age. For fluconazole efficacy studies, CLSI guidelines on drug susceptibility testing were used. To understand the susceptibility pattern, various molecular and structural analytic approaches, including sequencing, in silico site-directed mutagenesis, and protein-ligand profiling, were applied to the ERG11 gene and CYP51 protein sequences. Several platforms, comprising Clustal Omega, Pymol plugin manager, Pymol molecular visualizer, Chimera–curated Dynameomics rotamer library, protein–ligand interaction profiler, Charmm36 force field, GROMACS, Geneious, and Mega7, were employed for this analysis.Results: The following Candida species distribution was obtained: 37.84% C. albicans, 8.12% C. glabrata, 10.81% C. krusei, 5.41% C. tropicalis, and 37.84% of other unidentified Candida species. Two codons in the nucleotide sequence of the wild-type (CTC and CCA) coding for LEU– 370 and PRO– 375, respectively, were mutated to L370S and P375H in the resistant strain. The mutation stabilized the protein at the expense of the heme moiety. We found that the susceptible isolate from dogs (Can–iso– 029/dog) is closely related to the most resistant isolate from humans.Conclusion: Taken together, our results showed new mutations in the heme-binding pocket of caCYP51 that explain the resistance to fluconazole exhibited by the Candida isolates. So far, the L370S and P375H resistance-linked mutations have not been previously reported.Keywords: Candida infection, CYP51, drug resistance, ERG11, fluconazole, mutation

The use of caspofungin in neonates is beyond the instructions. Therefore, a retrospective analysis was performed to investigate the hepatic safety of caspofungin during the treatment of fungal diseases in neonates. A retrospective analysis was conducted on 23 neonates with Candida infection who were treated or prevented with caspofungin. Among the 23 neonates treated with caspofungin, 13 cases were cured (57%), and 10 cases showed improvements (43%). In addition, there were no adverse reactions associated with drug use, such as gastrointestinal tract, thrombocytopenia, and liver function damage. In summary, caspofungin achieved good results in the treatment or prevention of Candida infection in neonates, and no severe adverse reactions closely related to its use were found. However, the economy and safety of antifungal drugs should be considered in clinical practice for reasonable use. [ABSTRACT FROM AUTHOR]

Rapid identification of pathogens is required for early diagnosis and treatment of life-threatening bloodstream infections in humans. This requirement is driving the current developments of molecular diagnostic tools identifying pathogens from human whole blood after successful isolation and cultivation. An alternative approach is to determine pathogen-specific signatures from human host immune cells that have been exposed to pathogens. We hypothesise that activated immune cells, such as neutrophils, may exhibit a characteristic behaviour — for instance in terms of their speed, dynamic cell morphology — that allows (i) identifying the type of pathogen indirectly and (ii) providing information on therapeutic efficacy. In this feasibility study, we propose a method for the quantitative assessment of static and morphodynamic features of neutrophils based on label-free time-lapse imaging data. We investigate neutrophil activation phenotypes after confrontation with fungal pathogens and isolation from a human whole-blood assay. In particular, we applied a machine learning supported approach to time-lapse microscopy data from different infection scenarios and were able to distinguish between Candida albicans and C. glabrata infection scenarios with test accuracies well above 75%, and to identify pathogen-free samples with accuracy reaching 100%. These results significantly exceed the test accuracies achieved using state-of-the-art deep neural networks to classify neutrophils by their morphodynamics.

Erosio interdigitalis blastomycetica (EIB) is a Candida infection affecting the third web space, between the third and fourth fingers. In 1915, Gougerot and Goncea first described saccharomycetic organisms isolated from the hands and feet. Johannes Fabry later named it in 1917, well before the genus Candida was introduced in 1923. EIB is most common among those who work with their hands frequently in water, such as dishwashers, launderers, bartenders, and homemakers. Clinical presentation most commonly consists of a central erythematous erosion surrounded by a rim of white macerated skin involving at least one interdigital web space. The differential diagnosis is narrow, consisting of irritant contact dermatitis (ICD), erythrasma, inverse psoriasis, and bacterial infection (i.e. impetigo). The diagnosis is made by clinical examination in addition to fungal culture and KOH testing. The prognosis is good and treatment options include avoidance of frequent water immersion and topical or oral antifungal agents. Suspicion for secondary infections such as erysipelas and cellulitis should remain high until lesions have resolved. This review aims to address the history, epidemiology, pathophysiology, histopathology, clinical presentation, differential diagnoses, diagnosis, prognosis, and management of EIB. It also suggests an alternative name in place of the current misnomer.

We present the case of a 55-year-old female patient with metamizole-induced agranulocytosis after total knee arthroplasty, leading to septic periprosthetic joint infections (PJIs). Owing to metamizole-induced agranulocytosis, the synovial leukocyte count was negative. Here, we discuss the diagnostic challenges evolving from sepsis and neutropenia in patients with suspected PJIs. We suggest an urgent surgical approach, mainly focusing on the clinical presentation preoperatively. Later, our patient developed candidemia and periprosthetic tissue samples were positive for Candida albicans. For fungal PJIs, long-term follow-up studies are lacking and therapeutic recommendations differ. Here, we present our therapeutic approach, including staged revision and 12 weeks of systemic antifungal therapy, and discuss recent findings regarding the therapy of fungal PJIs.

Abstract Background (1,3)-β-d-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis. Methods This was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-β-d-glucan was negative ((1,3)-β-d-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-β-d-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment. Results We randomized 108 patients into the (1,3)-β-d-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1–3] in the (1,3)-β-d-glucan group vs. 10 days [6–13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94–8.65], p

A vaginal yeast infection called vaginal candidiasis is the most commonly seen type of Candida infections with a rate of 37%. Vaginal candidiasis affects three fourth (75%) of women in their lifetimes, and this is the most common cause of women seeking gynecological care. Vaginal candidiasis can result in serious symptoms such as discharge, itching, burning sensation, pain, rash and irritation in the vagina and vulva. Candida albicans, in particular, is the most common cause of vaginal candidiasis. Therefore, the treatment and control process of Candida species is very important in terms of health. In this study, as a first step, Microbial Chondroitin Sulfate was produced from Escherichia coli C2987 strain by using a specific microbial system and reliable biotechnological methods. After that, the efficacy of Microbial CS as an antifungal agent on C. albicans strains was tested by using the agar dilution method. As a result, it was determined that the Microbial CS was particularly effective against the yeasts C. albicans, and the minimum inhibitory concentration of Microbial CS was 0.32 g/mL. Our findings showed that Microbial CS can be used in the content of various biomedical products that can be used as an antifungal agent for Candida sp. Microbial CS can also be used to treat the disease alone or to support the treatment that increases the efficacy of antibiotics. [Med-Science 2020; 9(2.000): 433-6]

BackgroundCandida infection is prevalent in patients with Sjögren's syndrome (SjS), which usually takes years to reach diagnosis. Is the link a two-way street? The role of Candida infection before SjS has not been examined clearly. This study was conducted to provide epidemiological evidence regarding the relationship between the first acquisition of Candida infection and subsequent SjS.MethodsTotally, 23,494 individuals newly diagnosed with Candida infection were enrolled from 2000, to 2012. Controls (N = 93,976) were selected at a 1:4 ratio through propensity score matched (PSM) using the greedy algorithm. Exposure was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.Main Outcomes and MeasuresSjS was recorded in the Registry for Catastrophic Illness Patients Database (RCIPD). Cox proportional hazard model was used to analyze the association and sensitivity analyses for cross-validation.ResultsOf 117,470 individuals (106,077 [89%] women), 23,494 individuals (20.0%) had Candida infection and 104 individuals (0.1%) developed SjS. The incidence of SjS was higher in the exposed group compared with the controls (1.92 vs. 0. 98 per 10,000 person-years) with adjusted hazard ratio (aHR) 1.90 (95% CI, 1.25–2.87). The aHRs in subgroups of aged 18–30 years, oral candidiasis and depression were 4.30 (95% CI, 1.60–11.55), 4.70 (4.70–13.93) and 6.34 (2.16–18.66). Sensitivity analyses yield consistent results.ConclusionsResidents in Taiwan with Candida infection have higher risk of SjS. For early diagnosis of SjS, clinicians are advised to take Candida infection into account in some situation.

probiotic genomic characterization Limosilactobacillus fermentum Candida infectionLimosilactobacillus fermentum (ATCC 23271) was originally isolated from the human intestine and has displayed antimicrobial activity, primarily against Candida species. Complete genome sequencing and comparative analyses were performed to elucidate the genetic basis underlying its probiotic potential. The ATCC 23271 genome was found to contain 2,193,335 bp, with 2123 protein-coding sequences. Phylogenetic analysis revealed that the ATCC 23271 strain shares 941 gene clusters with six other probiotic strains of L. fermentum. Putative genes known to confer probiotic properties have been identified in the genome, including genes related to adhesion, tolerance to acidic pH and bile salts, tolerance to oxidative stress, and metabolism and transport of sugars and other compounds. A search for bacteriocin genes revealed a sequence 48% similar to that of enterolysin A, a protein from Enterococcus faecalis. However, in vitro assays confirmed that the strain has inhibitory activity on the growth of Candida species and also interferes with their adhesion to HeLa cells. In silico analyses demonstrated a high probability of the protein with antimicrobial activity. Our data reveal the genome features of L. fermentum ATCC 23271, which may provide insight into its future use given the functional benefits, especially against Candida infections. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the administration regimen of caspofungin in children based on Monte Carlo simulation, so as to provide reference for individualized administration. METHODS: Pediatric patients were grouped according to age, combined with the distribution of the minimum inhibitory concentration(MIC) of caspofungin against Candida and Aspergillus and the population pharmacokinetic parameters of caspofungin in pediatric patients, Crystal Ball 11. 1. 2. 2 software was used to simulate different administration regimens of children in different age groups based on Monte Carlo model. The probability of targe attainment(PTA) and cumulative fraction of response(CFR) were used as evaluation indicators. RESULTS: The daily maintenance dose of caspofungin was 50 mg / m², and the maximum daily dose was 70 mg. In different age groups, for Candida infection, when the MIC value was ≤0. 06 μg / ml, the therapeutic effect could be satisfied. In this case, treatment of C. albicans, C. glabrata and C. tropicalis could meet CFR>90%, while CFR values for C. krusei ranged from 80% to 90% and <20% for C. glabrata. In contrast, for Aspergillus infection, MIC values ≤ 0. 015 μg / ml were required to meet the therapeutic effect, but none of the CFR values reached 80%. CONCLUSIONS: Caspofungin had strong activity against C. albicans, C. glabrata and C. tropicalis, and its CFR value is related to the distribution of MIC. The combination of population pharmacokinetics and Monte Carlo model, and the implementation of individualized dosing regimens can ultimately achieve the desired therapeutic effect in individual children [ABSTRACT FROM AUTHOR]

Abstract Background The present meta-analysis examined the diagnostic accuracy of T2 Candida for candidiasis. Methods The literature databases, such as PubMed, Embase, DVIO, Cochrane library, Web of Science, and CNKI, were searched on T2 Candida detection. Results A total of 8 articles, comprising of 2717 research subjects, were included in the study. The pooled sensitivity and specificity were 0.91 (95% confidence interval (CI): 0.88–0.94) and 0.94 95% CI: 0.93–0.95), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 10.16 (95% CI: 2.75–37.50) and 0.08 (95% CI: 0.02–0.35), respectively. The combined diagnostic odds ratio is 133.65 95% CI: 17.21–1037.73), and the AUC of SROC is 0.9702 [(SE = 0.0235), Q* = 0.9201(SE = 0.0381)]. Conclusions The current evidence supported that T2 Candida has high accuracy and sensitivity and is of major clinical significance in the diagnosis of Candida infection.

Linear gingival erythema (LGE), formally referred to as HIV gingivitis, is the most common form of HIV associated periodontal disease in the HIV infected population. There is now evidence that this disease also occurs in HIV negative immunocompromised individuals and is not specific to HIV infection. A 13 years old boy presented with gingival inflammation in upper and lower anterior teeth mimicking LGE, but blood investigations showed HIV negative status. The microbial sample from the affected area confirmed candida infection and antifungal therapy with scaling helped to resolve the lesion. This case report emphasis that the clinician should obtain an in depth medical history to investigate such a condition. If there are signs and symptoms suggesting a systemic disease such as HIV, appropriate diagnostic testing such as blood testing or cytology must be considered. Patients with LGE should undergo laboratory testing to ensure that any underlying disorder is diagnosed and treated at the earliest possible time.

Background: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival. Method: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon ,Spain and the United States, to assess the duration of IV therapy and appropriate time to step down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down. Results: Candida albicans contributed to 45% bloodstream infection versus 55% infection caused Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p 5 days of treatment (24% mortality - p = 0.75). Conclusion: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.

Background: Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. Methods: Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014‐31 December 2017 were studied for 18 months post‐transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. Results: Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty‐nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51‐12.38), P =.0064. Conclusions: Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant. [ABSTRACT FROM AUTHOR]

Early identification of human pathogens is crucial for the effective treatment of bloodstream infections to prevent sepsis. Since pathogens that are present in small numbers are usually difficult to detect directly, we hypothesize that the behavior of the immune cells that are present in large numbers may provide indirect evidence about the causative pathogen of the infection. We previously applied time-lapse microscopy to observe that neutrophils isolated from human whole-blood samples, which had been infected with the human-pathogenic fungus Candida albicans or C. glabrata , indeed exhibited a characteristic morphodynamic behavior. Tracking the neutrophil movement and shape dynamics over time, combined with machine learning approach, the accuracy for the differentiation between the two Candida species was about 75%. In this study, the focus is on improving the classification accuracy of the Candida species using advanced deep learning methods. We implemented (i) gated recurrent unit (GRU) networks and transformer-based networks for video data, and (ii) convolutional neural networks (CNNs) for individual frames of the time-lapse microscopy data. While the GRU and transformer-based approaches yielded promising results with 96% and 100% accuracy, respectively, the classification based on videos proved to be very time-consuming and required several hours. In contrast, the CNN model for individual microscopy frames yielded results within minutes, and, utilizing a majority-vote technique, achieved 100% accuracy both in identifying the pathogen-free blood samples and in distinguishing between the Candida species. The applied CNN demonstrates the potential for automatically differentiating bloodstream Candida infections with high accuracy and efficiency. We further analysed the results of the CNN using explainable artificial intelligence (XAI) techniques to understand the critical features and patterns, thereby shedding light on potential key morphodynamic characteristics of neutrophils in response to different Candida species. This approach could provide new insights into host-pathogen interactions and may facilitate the development of rapid, automated diagnostic tools for differentiating fungal species in blood samples., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Worldwide Candida albicans infections cause a huge burden in healthcare and the efficacy of traditional antifungals is diminished because of the rapid development of antifungal resistance. It is necessary to develop new antifungals or new strategies to make multidrug-resistant (MDR) C. albicans to resensitize to existing antifungal drugs. In this work, a series of 4-arm polypeptoids (FAPs) were synthesized through grafting linear ε-l-lysine or δ-ornithine-based oligopeptides to a trimeric lysine core. The most potent 4R-O7 exhibited excellent activities toward three sensitive and two MDR C. albicans strains with MIC values as low as 24-48 μg/mL (vs 375 μg/mL for ε-polylysine, ε-PL). The mechanism studies revealed that 4R-O7 penetrated the cell membrane and generated ROS to kill cells. 4R-O7 exhibited a synergistic effect (FICI < 0.5) with voriconazole (VOR) and also assisted VOR to restore its efficacy to MDR C. albicans . In addition, the combined use of 4R-O7 and VOR significantly improved the elimination efficacy of mature C. albicans biofilms and enhanced the potency in a mouse subcutaneous C. albicans infection model.

Objective To investigate the effective diagnosis and treatment of deep neck bacterial infection combined with fungal infection. Methods The clinical data of 1 case of deep neck bacterial infection combined with fungal infection were retrospectively analyzed. Results The patient went to the doctor with a chief complaint of sore throat for 4 days accompanied by fever for half a day; the clinical examination revealed swelling in the left mandibular and neck soft tissues; leukocyte, neutrophil %, and C-reactive protein were all elevated; CT examination revealed soft tissue swelling in the left epiglottis, and gas accumulation in the left oropharyngeal lateral wall, the left face, both submandibular, left neck and upper mediastinal space. There was no improvement in the anti-infection treatment with cefathiamidine and ornidazole. Considering parapharyngeal space infection and the possibility of infection by aerogenic bacteria in the deep cervical space, the antibacterial agents were replaced of cefepime and ornidazole, and meanwhile, tracheotomy and neck exploration, incision and drainage surgery were performed. The pus culture indicated the mixed infection of Klebsiella oxytoca, Streptococcus constellation and Candida albicans, and the blood culture indicated candida infection, which was diagnosed as deep neck bacterial infection combined with fungal infection. Then the neck abscess was treated with expanded drainage guided by ultrasound, and the antibiotics were adjusted to meropenem and vancomycin and ornidazole, and caspofungin was used to fight fugal infections. The patient was cured and discharged from the hospital. Conclusions The main symptoms of deep neck bacterial infection combined with fungal infection were fever, pharyngeal pain, swelling and pain of mandibular and neck soft tissues. Hemogram increased and CT scan of the neck showed local soft tissue swelling and air accumulation in the muscle space. The effect of empirical anti-infection treatment was not good. The method of definite diagnosis was bacterial and fungal culture of local pus. The effective treatment was to give enough sensitive antibiotics and antifungal drugs at the same time, and local incision and drainage could be done if necessary. [ABSTRACT FROM AUTHOR]

The lifetime prevalence of peptic ulcer disease (PUD) is 5–10%. While PUD in immunocompetent patients is most commonly associated with Helicobacter pylori infection or the use of non-steroidal anti-inflammatory drugs (NSAIDs), other common causes of PUD must also be considered in the differential diagnosis. We describe a case of endoscopic and histological resolution of PUD related to Candida infection in a healthy, immunocompetent woman.

Purpose: Caspofungin is prescribed for systemic treatment of fungal infections and correct prescription pattern is an issue of importance. Hence in this study the Caspofungin utilization and the frequency rate of medication errors were investigated at a training hospital in a developing country. Methods: In this cross-sectional descriptive comparative study 43 consecutive patients receiving Caspofungin in Firoozgar Hospital, Tehran, Iran from March to September 2017 were enrolled. The prescription frequency of the drug was compared with the national data and the suggested rates by World Health Organization. Results: The prescription rate was higher in Intensive Care Unit with 72.1% rate. Infectious disease specialists were responsible for Caspofungin prescription only in 11 cases (25.5%). The cause of Caspofungin prescription was unknown in 18.6% of cases; but experimental treatment for febrile neutropenia and ICU patients with Candida Score > 2.5 were the most known causes. The drug administration in 11 cases (25.6%) occurred in less than one hour. The indication of treatment was incorrect in 12 out of 43 cases (28%). On the first day of the treatment a dose of both 70 mg and 50 mg was prescribed, which was higher than the appropriate dose and also it was lower than the optimal dose in five cases (83.7%). The mean treatment duration was 10.88 ± 5.35 days ranging from 2 to 24 days. The duration of treatment was correct in 20 cases (46.5%) and incorrect in 23 patients (53.5%). Conclusion: According to the obtained results, it may be concluded that in comparison with the international guidelines there are multiple discordance in our setting including inappropriate duration, continuation, and indications. Hence these should be announced to the physicians for further cautions in this area, and it is better to consult with infectious diseases specialists for the administration of anti-fungal drugs.