Background and Purpose:Scedosporium apiospermum, a soil-dwelling fungus, is typically associated with localized infections, such as skin infections and osteomyelitis. However, it can also cause invasive central nervous system infections, including brain abscesses, particularly in immunocompromised individuals. Such infections are rare in immunocompetent individuals and often occur following trauma or environmental exposure. This report aimed to present a case of a fatal S. apiospermum brain abscess in an immunocompetent adult male, highlighting diagnostic and management challenges. Case presentation:A 48-year-old immunocompetent male presented with a three-day history of persistent holo-cranial headache and left-sided weakness. Twenty days earlier, the patient had fallen into a sewer, likely exposing him to fungal pathogens. Initial imaging revealed a large right frontal intracranial lesion. Surgical resection of the abscess was performed, and antifungal therapy with voriconazole was initiated. Intraoperative findings revealed a thick, non-vascular abscess capsule containing yellow pus. Postoperative KOH mount confirmed fungal elements (hyaline septate hyphae). Despite aggressive management in the intensive care unit, including antifungal therapy, antibiotics, and supportive care, the patient developed septic shock and succumbed to cardiac arrest within 48 h of surgery. Conclusion:This case underscores the rapid progression and severity of S. apiospermum infections in immunocompetent individuals, even with early surgical and medical intervention. It emphasizes the need for heightened clinical suspicion in cases involving trauma with potential environmental exposure. Prompt diagnosis, effective antifungal therapy, and multidisciplinary management are essential to improve outcomes in such cases.
Background and Purpose:Rapid and accurate identification of molds is critical in clinical microbiology, particularly for immunocompromised patients at increased risk of fungal infections. Traditional methods, such as culture and microscopy, are time-consuming and may lack species-level specificity. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides a promising alternative due to its speed and accuracy. This study aimed to standardize Vitek MS for mold identification and compare its effectiveness with traditional phenotypic methods, assessing its reliability, turnaround times, and cost-effectiveness in clinical settings. Materials and Methods:A retrospective examination of 248 anonymized mold isolates was conducted at Hinduja Hospital, with 182 isolates successfully revived. Both Vitek MS and phenotypic techniques were used to identify the molds, and the concordance rate between the two methods was calculated. Results:Vitek MS accurately identified 169 out of the 182 isolates, yielding a concordance rate of 92.85% with phenotypic methods. Of the remaining isolates, 1 was misidentified, 4 could not be identified, and 8 were not represented in the database. Conclusion:Vitek MS proved to be a highly accurate and time-efficient tool for mold identification, enhancing clinical diagnostics. Expansion of its database is crucial for broader mold identification. This study supported integration of Vitek MS into routine laboratory practice, aiding in timely antifungal treatment, improving patient outcomes, and assisting in outbreak detection and public health management.
Background and Purpose:Invasive fungal infections have high morbidity and mortality rates, with Candida species being the leading cause in hospitalized patients. Virulence factors, such as adhesion, enzyme secretion, and biofilm formation, play a major role in Candida pathogenesis. This study hypothesized that virulence factors in localized Candida infections behave differently than those in systemic infections. Materials and Methods:This study compared invasive and non-invasive Candida clinical isolates in terms of biofilm formation and enzymatic activity in. Biofilm mass and metabolic activity were assessed using crystal violet and XTT assays, while phospholipase and protease activities were measured in specific media. Qualitative biofilm characterization was performed using scanning electron microscopy and scanning confocal laser microscopy. Results:Candida isolates from invasive infections showed higher bulk biofilm production and metabolic activity, compared to localized infection isolates. Bulk biofilm production and metabolic activity were notably higher in systemic infections, compared to those in localized infections. Non-albicans Candida species exhibited a higher biofilm-forming capacity and metabolic activity, emphasizing their potential for more invasive infections. Conversely, hydrolytic enzyme production was higher in localized infection isolates, compared to that in systemic infection. Phospholipase activity showed no significant differences. Conclusion:The differences in enzymatic activity observed in isolates from various anatomical sites underscores the importance of considering the infection context in assessing virulence These findings highlight the role of proteases and other factors in Candida invasiveness, contributing new insights into Candida virulence factors in Ecuador.
Background and Purpose:With the increasing number of fungal infections due to antibiotic use and growing numbers of immunocompromised patients, it has become imperative to understand the nature of these infections. Fungal infections, however, remain largely understudied and underdiagnosed, especially when it comes to co-infections with other organisms. This study aimed to compare inflammatory biomarkers in fungal pneumonia patients with and without bacterial co-infections and analyze the frequencies of the causative bacterial and fungal organisms. Materials and Methods:This retrospective study used electronic medical records from patients diagnosed with fungal pneumonia from January 2013 to December 2023. Fungal and bacterial etiologies were identified with International Classification of Diseases-10 codes and summarized with descriptive statistics. Baseline characteristics, comorbidities, and length of stay were analyzed using descriptive statistics and the Chi-squared test. Inflammatory biomarkers, including C-reactive protein, erythrocyte sedimentation rate, procalcitonin, white blood cell count, body temperature, ferritin, and electrolytes, were collected using Current Procedural Terminology codes and compared using Chi-squared test between patients diagnosed with fungal pneumonia alone or with fungal pneumonia and bacterial co-infection. Results:A total of 1,024 patients were diagnosed with fungal pneumonia. The most common diagnosis among the patients was unspecified mycosis. Moreover, the most common organism-specific mycotic disease was pneumocystosis. Comorbidities, including diabetes and chronic inflammatory disease, were more common in patients with co-infection (p < 0.05). None of the inflammatory biomarkers investigated were statistically significant. Conclusion:Lack of specificity of most fungal organisms responsible for pneumonia highlights the critical lack of specific diagnostic methods for fungal diseases. The results show that inflammatory biomarkers are not significantly different between fungal pneumonia patients with and without bacterial co-infections.
Background and Purpose:Pathogenic fungi, including both true and opportunistic pathogens, pose significant health risks, particularly in immunocompromised individuals. Species, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, cause fatal infections and frequently develop resistance to conventional antifungal therapies. Limitations of current antifungal medications, such as drug toxicity, resistance development, and environmental concerns, highlight the urgent need for novel therapeutic strategies. Earthworm extracts, particularly those derived from Eisenia fetida, have been recognized as a promising alternative in traditional Chinese medicine. This study aimed to assess the antifungal effects of a peptide extract from E. fetida against these opportunistic fungal pathogens. Materials and Methods:The earthworm extract was obtained from E. fetida through electroporation and centrifugation to isolate bioactive components. Composition of the extract was analyzed in detail; accordingly, protein content was determined using the Bradford and Kjeldahl methods, fat content was measured via Soxhlet extraction, and moisture, dry matter, and ash contents were also quantified to provide a comprehensive profile. To evaluate antifungal activity, fungal cultures of A. fumigatus, C. albicans, and C. neoformans were grown on Sabouraud dextrose agar. The disk diffusion method was used to assess antifungal activity by measuring inhibition zones surrounding extract-containing disks. A dilution series of the E. fetida extract was also prepared to further analyze antifungal effects. The broth microdilution method was employed to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) for each fungal species, providing quantitative data on the effectiveness of the extract. Results:The coelomic fluid extracted from E. fetida contained 60.03% protein, 8.136% fat, 6.91% ash, 6.03% moisture, and 8.65% dry matter. Disk diffusion assays revealed significant inhibition of A. fumigatus and C. albicans, with the extract exhibiting stronger effects at higher concentrations. In broth microdilution assays, the extract achieved MIC/MFC values of 12.5%/25% against A. fumigatus and 3.125%/6.25% against Candida albicans. However, its efficacy against C. neoformans was lower, while the commercial antifungal drug, itraconazole, demonstrated superior efficacy against all tested strains. Conclusion:Earthworm extracts, rich in antimicrobial peptides, exhibit promising antifungal properties, particularly against C. albicans. Although not as effective as itraconazole, the potential of the extract as a safer and environmentally friendly alternative underscores its significance in antifungal research. Further studies are needed to enhance its efficacy and broaden its antifungal spectrum, potentially leading to new, sustainable strategies for managing fungal infections.
Over the past decade, there has been an increasing level of concern regarding Candida auris. This fungus was initially identified in the auditory canal of an elderly Japanese woman in a medical facility in Tokyo, Japan, in 2009. Over the course of the upcoming decade, the fungus emerged concurrently on four distinct continents, with each strain exhibiting sufficient genetic distinctiveness to dispel the notion of intercontinental disease transmission. With climate change, fungal infection rates have increased throughout the world. In the Indian subcontinent, the temperature has been rising over the years, which could be the leading reason for the increase in fungal infections. Hence, it is postulated that climate change can be the breeding ground for emerging fungal pathogens as they adapt themselves to high temperatures.
Background and Purpose:Candida lusitaniae is a rare cause of invasive candidiasis in children. This study aimed to investigate the clinical and microbiologic characteristics, treatment, and prognosis of C. lusitaniae candidemia in pediatric patients. Materials and Methods:This retrospective study included pediatric patients (<18 years) with bloodstream infections caused by C. lusitaniae at Balcalı Hospital, Faculty of Medicine, Cukurova University, Adana, Turkey from December 2013 to December 2021. Demographics, underlying diseases, risk factors, treatment regimens, and outcomes were analyzed. Antifungal susceptibility was tested using the VITEK® 2 Compact system. Catheter-related bloodstream infection was defined by standard criteria. Results:Among 395 candidemia episodes, C. lusitaniae accounted for 11 cases (2.7%). The median age was 16 months (range: 2-177 months). Most had underlying conditions (82%), primarily congenital heart disease (27.3%). Major risk factors included antibiotic use (100%), central venous catheter (91%), mechanical ventilation (63.6%), intensive care unit (ICU) stay (63.6%), nasogastric tube (45.4%), surgery history (45.4%), and H2 blocker use (45.4%). The median patient age was 16 months (range: 2-177 months), and all patients were male. Most patients (82%) had at least one underlying condition, with congenital heart disease being the most common (27.3%). The most frequently observed risk factors included recent antibiotic use (100%), central venous catheterization (91%), mechanical ventilation (63.6%), ICU admission (63.6%), nasogastric tube use (45.4%), surgical history (45.4%), and H2-receptor blocker administration (45.4%). Seven patients received antifungal monotherapy with fluconazole (4/7), L-AmB (1/7), caspofungin (1/7), and micafungin (1/7). Combination antifungal therapy was initiated in three patients (30%) due to persistent candidemia and delayed catheter removal. In these cases, combination regimens included fluconazole and caspofungin or L-AmB with additional agents. The mean duration of antifungal therapy was 28 days (range: 12-58 days). The median time to clearance of fungemia (negative blood culture) was 15.8 days (range: 3-45 days). Delays in catheter removal were often due to clinical instability or lack of alternative vascular access. One patient who received combination therapy died, resulting in an overall 30-day mortality rate of 9% (1/11). Conclusion:Candida lusitaniae is a rare nosocomial pathogen in children with underlying conditions and risk factors. Fluconazole remains a primary treatment option, although combination therapy may be warranted in refractory cases. Given the potential resistance to L-AmB, caution is advised in its use. Timely catheter removal is associated with improved outcomes. Further studies are needed to establish optimal therapeutic strategies for this rare infection.
Background and Purpose:Candida endocarditis, though rare, presents significant risks, especially in prosthetic valve recipients. Candida guilliermondii is an uncommon causative pathogen, necessitating a high index of suspicion, advanced diagnostics, and prompt antifungal therapy to improve patient outcomes. Case Presentation:A 57-year-old male with a history of rheumatic heart disease and prior mitral valve replacement presented with fever, chills, and generalized body aches for 10 days. Laboratory investigations revealed microcytic hypochromic anemia, while echocardiography demonstrated prosthetic valve vegetation with mild to moderate aortic regurgitation. Blood cultures confirmed C. guilliermondii infection. Conclusion:Early recognition, multidisciplinary collaboration, and tailored antifungal therapy are pivotal for favorable outcomes in C. guilliermondii prosthetic valve endocarditis. This case highlights the importance of comprehensive diagnostics and vigilant patient management to mitigate complications and improve prognosis.
Background and Purpose:Onychomycosis, a prevalent fungal infection affecting the nails, presents considerable difficulties in clinical treatment. Zataria multiflora (Zat), with its known antifungal properties, presents a promising approach for treatment. The present study focused on the evaluation of the effectiveness of Zat-NLC 1% gel against mold-associated onychomycosis, compared to a placebo. Materials and Methods:The Zat-loaded nanostructured lipid carriers (Zat-NLCs) were prepared and optimized by utilizing an ultrasonic probe approach. Antifungal susceptibility testing followed Clinical and Laboratory Standards Institute M38-A3 guidelines on the most common dermatophytes and non-dermatophytes fungal species. A double-blind trial with 40 participants (20 volunteers from each gender, equally divided into two groups, namely Zat-NLCs 1% gel and placebo receivers) evaluated Zat-NLC 1% gel efficacy. Causative agents were identified at the species level using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results:A mono-dispersed suspension of spherical nanoparticles with zeta potential, Z-average, and polydispersity index of -26.6±7.7 mV, 273.9±3 nm, and 0.369±0.03, respectively, was achieved with no cytotoxicity. The Zat-NLCs demonstrated a significant inhibitory effect on both dermatophytes and non-dermatophyte fungal growth, in vitro. Effective improvement was observed in mycological criteria, compared to the placebo group (P<0.005) after 2 weeks of treatment. The mycological cure rate was 70% for Zat-NLCs gel after only 2 weeks. The results were notably different from those observed in the placebo group following the same duration of application (70% vs. 55%). However, the difference was insignificant in the mentioned groups after 4 weeks of application due to the prescription of routine antifungals for onychomycosis. The PCR-RFLP outputs revealed T. mentagrophytes/interdigitale complex and A. section Flavi as the predominant isolated species of dermatophytes and non-dermatophytes, respectively. Conclusion:Nanoscale colloidal systems loading with antifungals might be strongly considered a better and more efficient cure for mold-related dermatophytosis.
Nano-graphene oxide is a promising Candidate for therapeutic applications, particularly due to its notable antifungal and antibacterial properties, which stem from the unique physicochemical characteristics of this innovative nanocarrier. Antifungal efficacy of nano-graphene oxide is increasingly attracting attention, particularly in light of the rising resistance of pathogens to conventional drug therapies. Upon exposure to graphene oxide, fungal cells generate reactive oxygen species, a key indicator of cellular oxidative stress. This mechanism accounts for the apoptotic-like cell death observed in the presence of graphene oxide. This nano-drug delivery system holds the potential to achieve therapeutic efficacy at reduced doses, minimize side effects, enable controlled drug release, prolong circulation time, reduce toxicity, and enhance the stability of the nano-formulation, particularly when administered as an inhaled dry powder. However, the factors influencing the antifungal activity of nano-graphene oxide and the underlying mechanisms remain poorly understood. This article aimed to review the anti-pathogenic properties of nano-graphene oxide, focusing on its antifungal mechanisms and its role in biofilm formation associated with pulmonary fungal infections.
Background and Purpose:Dermatophytosis, or ringworm, is a highly contagious fungal infection caused by dermatophytes, like Microsporum canis, which primarily affects cats and dogs and poses a significant zoonotic threat. Increasing prevalence of drug-resistant strains complicates the treatment of M. canis infections, necessitating the exploration of new therapeutic approaches. Nanotechnology, particularly copper oxide nanoparticles (CuO NPs), has emerged as a promising solution due to its potent antimicrobial properties and potential to overcome resistance. This study aimed to evaluate the antifungal efficacy of CuO NPs against M. canis isolates collected from companion animals. The goal was to develop more effective treatment options for dermatophytosis, addressing the need for alternative therapies and the challenge of antifungal resistance. Materials and Methods:CuO NPs were synthesized using a green chemistry approach, employing Eichhornia crassipes leaf extract. Concurrently, M. canis isolates were obtained from infected animals and cultured for purity. Antifungal activity of the CuO NPs against the isolates was assessed through disk diffusion and microdilution tests, and the results were statistically analyzed to confirm their significance. Cell dens (10 5 . Results:The synthesized CuO NPs exhibited high purity, small size, and cubic morphology. Statistical analysis of the disk diffusion and microdilution tests confirmed the significant antifungal efficacy of CuO NPs against M. canis isolates (ANOVA, p<0.05). Minimum inhibitory concentration (MIC) values ranged from 500 to 1,000 ppm, while minimum fungicidal concentration (MFC) values were between 1,000 and 2,000 ppm. Average MFC/MIC ratio of 2.6, confirmed through paired t-test (p=0.003), demonstrated the fungicidal properties of the CuO NPs. Conclusion:This study highlighted the potent antifungal capabilities of CuO NPs against M. canis, marking them as a promising alternative to conventional treatments. With further optimization and research, CuO NPs could revolutionize the management of dermatophytosis, offering a new frontier in combating drug-resistant fungal infections.
Background and Purpose:Fluconazole resistance in Candida species is on the rise, posing a significant clinical challenge. There is a growing interest in using complementary therapies, especially those from natural sources. This study aimed to evaluate the synergistic and apoptotic effects of Bunium persicum essential oil (BPEO) and its two pure components, cuminaldehyde (CA) and γ-terpinene (γ-TPN), combined with fluconazole (FLC) on susceptible and resistant C. albicans isolates. Moreover, molecular docking was used to study the interactions between lanosterol 14-alpha-demethylase and each agent. Materials and Methods:The BPEO was prepared using the Clevenger apparatus and the hydro-distillation method. The in vitro antifungal activity was evaluated according to the Clinical and Laboratory Standards Institute guideline (M60). The checkerboard and isobologram assays assessed the interaction between BPEO, CA, γ-TPN, and FLC. The necrotic and apoptotic effects of different agents were analyzed using a flow cytometry assay. An in-silico study was performed to examine the receptor-ligand interaction. Results:The CA showed the lowest minimum inhibitory concentrations and minimum fungicidal concentrations, compared to BPEO and γ-TPN. Statistical analyses indicated significant differences between resistant and sensitive C. albicans isolates regarding minimum inhibitory concentration values of BPEO, CA, and γ-TPN. The most synergistic effect was obtained for FLC combined with CA (n=7, 63.6%), followed by BPEO (n=6, 54.5%), and γ-TPN (n=3, 27.2%). Statistical analyses indicated the synergistic effect of FLC in combination with CA was more than γ-TPN (p=0.023). Apoptotic indicators confirmed that the tested compounds could cause cell death in yeast cells. Combination of each natural component with FLC resulted in a greater apoptosis effect than each tested agent alone. The docking study indicated that both pure compounds have interactivity with the protein residue of 14α-demethylase. Conclusion:The results indicated that the synergistic properties of natural products combined with synthetic antifungal agents available in the market could contribute to developing effective therapeutic strategies, particularly in resistant fungal species.
Background and Purpose:The current study aimed to assess the demographic features, clinical characteristics, species diversity, and contributing factors among patients with severe acute respiratory syndrome coronavirus-2 pneumonia-associated mucormycosis in northwestern Iran. Materials and Methods:This cross-sectional descriptive study was performed on patients who tested positive for COVID-19 via reverse-transcriptase-polymerase chain reaction and were suspected of having invasive fungal infection. Mucormycosis was confirmed by histopathology of biopsy samples and species identification was performed using morphological and internal transcribed spacer-rDNA sequencing methods. Results:Mucormycosis was observed in 63 COVID-19 patients. Mean age of patients was 56.65±14.49 years (range of 22-85 years) and 63.5% of the involved patients were male. The most common involvement site of patients with mucormycosis was the sinus (63.5%). Among all participants, 84% of patients (n=53) had received intravenous dexamethasone, and 25.4% of them had diabetes mellitus. All patients with proven invasive mucormycosis received intravenous amphotericin B. In total, 21 (33%) positive cultures were identified and Rhizopus arrhizus was the main causative agent. Conclusion:Awareness among physicians should be raised that corticosteroid therapy not only causes dysfunction of the immune system but may also lead to the development of this neglected mycosis through corticosteroid-induced diabetes in vulnerable patients.
Background and Purpose:The high morbidity and mortality caused by invasive mold infections require new and effective treatment strategies. Heat shock proteins, which are found in all living organisms, play a role in the homeostatic control of the cell and the stress response mediated by calcineurin. Their release increases especially under stress conditions, and they play a role in ensuring the stability of cellular proteins. Therefore, inhibition of Hsp90 or calcineurin may be an effective method in antifungal therapy. This study aimed to evaluate the in vitro activity of four different antifungal agents (caspofungin, amphotericin B, itraconazole, and voriconazole) in combination with fungal stress response regulators, Hsp90 inhibitors, and calcineurin inhibitors, against clinical isolates of Aspergillus, Rhizopus, and Fusarium. Materials and Methods:In this study, the effectiveness of Hsp90 inhibitors geldanamycin, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), radicicol, novobiocin (NOV), and calcineurin inhibitors cyclosporine, tacrolimus (TAC), and rapamycin (RAP) combined with common antifungals itraconazole (ITRA), voriconazole (VOR), caspofungin (CAS), and amphotericin B (AMB) were investigated against four Aspergillus, three Rhizopus, and three Fusarium isolates using checkerboard method. Results:The minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) values of ITRA, VOR, CAS, and AMB were ≤ 0.25, ≤ 0.06-0.125, ≤ 0.03-> 4, and 1-4 µg/mL for Aspergillus spp.; 2-8, > 4, > 4, and 2 µg/mL for Rhizopus spp.; 8- > 16, 1-4, > 4, and 2-4 µg/mL for Fusarium spp., respectively. Although tacrolimus was found to have generally low MIC values (≤0.03 µg/mL) for Aspergillus and Rhizopus isolates, NOV, and 17-AAG did not exhibit antifungal activity (MICs>128 and ≥16 µg/mL, respectively) against almost all of the isolates. In combination testing against Aspergillus and Rhizopus spp., synergistic interactions were prevalent (≥75%) for the combinations of ITRA and all inhibitory substances, except for TAC. The effects of CAS and TAC in combination tests were weak. Moreover, synergistic interactions were not frequent in all combinations against Fusarium spp. However, antagonistic interaction was observed only in one ITRA and RAP combination throughout this study. Conclusion:The Hsp90 and calcineurin inhibitors did not have significant antifungal activity alone. Moreover, they did not show a significant antagonistic effect in combination and even increased the efficacy of antifungals at some concentrations.
Background and Purpose:Histoplasmosis, caused by Histoplasma capsulatum, typically presents as a pulmonary infection but can disseminate, with oral lesions being common among immunocompromised individuals. However, this is rare among immunocompetent patients. Preferred treatments include itraconazole for mild cases and liposomal amphotericin B for severe forms. Case presentation:This study aimed to report a 28-year-old female who developed disseminated histoplasmosis following a right oroantral fistula after dental surgery. It was initially misdiagnosed as Actinomycosis; however, a positive urinary Histoplasma antigen test confirmed histoplasmosis. Despite itraconazole therapy (200 mg twice daily, later increased to 600 mg), her condition continued to deteriorate, with disease progression seen on imaging. Switching to six weeks of intravenous liposomal amphotericin B led to marked improvement, resolution of lung nodules, and negative antigen testing. She was discharged with a 12-month course of itraconazole therapy. Conclusion:This case highlights the importance of timely recognition and adjustment of treatment in non-severe histoplasmosis, particularly for patients who do not respond adequately to itraconazole therapy.
Background and Purpose:Fungal endometritis, an uncommon yet severe condition affecting the uterine lining, typically manifests with abnormal uterine bleeding (AUB), pelvic discomfort, and vaginal discharge. This investigation aimed to present a pioneering study focused on fungal endometritis in women presenting with these clinical symptoms. Materials and Methods:A cohort of 43 female patients experiencing abnormal uterine bleeding was comprehensively evaluated at Babol University of Medical Sciences in Babol, Iran, between March 21, 2023, and March 19, 2024. Diagnostic procedures encompassed ultrasound imaging, a range of laboratory tests, hysteroscopy for direct visualization and tissue sampling, microscopic examination, fungal culture with subsequent colony count, and polymerase chain reaction for enhanced accuracy in fungal identification. Additionally, drug susceptibility patterns were assessed for all isolated fungal species. Results:Among the 43 patients, five (11.62%) received a definitive diagnosis of fungal endometritis. The identified species included two isolates of Candida albicans, two isolates of Nakaseomyces glabratus (previously known as C. glabrata), and one isolate of Candida orthopsilosis. A notable diagnostic observation was that all confirmed cases yielded negative results from vaginal discharge cultures, emphasizing the necessity of direct endometrial sampling. Antifungal susceptibility testing revealed varying minimum inhibitory concentrations among the isolates, though all responded effectively to the combined treatment of voriconazole and surgical debridement. Conclusion:This study highlighted the critical importance of prompt evaluation and precise diagnosis, including comprehensive antifungal susceptibility testing, in individuals presenting with acute endometritis and AUB. Such rigorous considerations are essential for guiding clinical management and mitigating the risk of adverse outcomes, particularly given the increasing antifungal resistance and the emergence of non-albicans Candida species as significant pathogens.
Background and Purpose:Candidemia is a prevalent nosocomial bloodstream infection with a high mortality rate. Involvement of heart valves by Candida spp. after candidemia can result in native and prosthetic valve endocarditis as biofilm-related infections. Case Report:This report aimed to introduce a case of a 13-year-old male with bloodstream infection and prosthetic valve endocarditis, caused by itraconazole-resistant Candida glabrata (Nakaseomyces glabratus). Despite undergoing itraconazole for 4 weeks, the patient did not improve. White colonies were identified as C. glabrata (N. glabratus) by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction. The isolate was resistant to itraconazole (MIC=8 µg/mL) but susceptible to amphotericin B and caspofungin. Based on concerns about biofilm-related resistance, treatment was switched to caspofungin for 5 weeks. He continued to do well and showed no signs of relapse during his 6-month follow-up. Conclusion:This study explored the importance of antifungal susceptibility testing in handling complicated infections, as well as the potential of caspofungin in the treatment of cases of fungal bloodstream infections and endocarditis.
Background and Purpose:Fungal infections necessitate advanced delivery systems to improve antifungal therapy. Terbinafine, a potent allylamine antifungal, faces clinical limitations due to poor solubility, low bioavailability, and toxicity. Liposomal encapsulation addresses these challenges by enhancing solubility, enabling controlled release, and reducing toxicity. In this study, a scalable ethanol injection method was used to develop terbinafine-loaded liposomes with optimized physicochemical properties. This study aimed to focus on central nervous system-targeted delivery to combat resistant fungal infections while minimizing systemic toxicity. Materials and Methods:Twenty liposomal formulations were prepared using phospholipids (e.g., dipalmitoylphosphatidylcholine [DPPC], hydrogenated soybean phosphatidylcholine) and characterized for size, zeta potential, polydispersity index, and morphology via dynamic light scattering and transmission electron microscopy. Encapsulation efficiency, drug release kinetics, colloidal stability (3 months), and cytotoxicity (human foreskin fibroblast 2 cells, 48-hour exposure) were evaluated. The M38-A2 method of the Clinical and Laboratory Standards Institute was used to calculate minimum inhibitory concentrations (MICs) of 16 azole-susceptible and -resistant Aspergillus fumigatus and Aspergillus flavus. Results:Liposomes exhibited sizes of 72-174 nm, zeta potentials between +2 and -15 mV, and a low polydispersity index (<0.3). Moreover, F12 (DPPC-based) demonstrated superior cumulative release, compared to F20, and attributed to the fluid bilayer of DPPC. Both formulations retained stability during storage. Cytotoxicity assays revealed minimal toxicity for free terbinafine (14.73% at 25 mg/mL) and significantly reduced toxicity for liposomal forms (6.77% for F12, p<0.05). The DPPC-based formulation achieved an encapsulation efficiency of 73.48%, ensuring a high drug payload and biocompatibility. The DPPC-based formulation achieved an encapsulation efficiency of 73.48%, ensuring a high drug payload and biocompatibility. Liposomal terbinafine and voriconazole exhibited good in vitro activity against both triazole-susceptible and -resistant Aspergillus isolates (MIC50=0.5 µg/mL). Conclusion:Based on the results, F12, with its sub-100 nm size, sustained release, and reduced cytotoxicity, emerged as a promising candidate for brain-targeted antifungal therapy. Its stability and high encapsulation efficiency support further evaluation in fungal isolates and in vivo models to optimize central nervous system biodistribution and therapeutic efficacy. In addition, this study underscored the promising in vitro activities of terbinafine and liposomal terbinafine against both triazole-resistant/susceptible A. fumigatus and A. flavus.
Background and Purpose:Fluconazole is one of the primary antifungal agents in the treatment of candidiasis. However, long-term treatment and indiscriminate use of drugs from the azole family have created resistant isolates. Candida albicans cells can develop resistance to fluconazole through various mechanisms. The present study aimed to investigate the expression of genes involved in fluconazole resistance in C. albicans in people with different underlying diseases. Materials and Methods:Databases, such as PubMed, Scopus, and Web of Science were used to collect studies evaluating the expression levels of key C. albicans genes associated with fluconazole resistance from 1997 to 2024. Finally, 25 out of the 1,096 extracted studies were selected based on the inclusion and exclusion criteria. Results:This systematic review identified the genes encoding the ATP-binding cassette membrane pump (CDR1, CDR2) and the genes encoding the major facilitator superfamily pumps (MDR1), as well as the ERG11 gene, are the most important effective genes in creating resistance of C. albicans to fluconazole. Based on the studies conducted since 1995, the CDR1 gene has the highest gene expression among the genes involved in resistance, followed by ERG11, MDR1, and CDR2, respectively. Conclusion:Comprehensive information about the activity of the genes and more studies on the genes involved in resistance, could provide valuable insights for further studies, prevent the occurrence of resistance to fluconazole and other azoles, and provide suitable treatments. The disease, as well as the dosage and duration of the antifungal therapy, may play an important role in determining the type of resistance mechanism of C. albicans. Therefore, further evaluation of the role of these genes in fluconazole-resistant species, along with their related gene products, is necessary.
Background and Purpose:One of the most severe mycotic infections caused by Candida spp. is invasive candidiasis. According to the literature, among all healthcare- associated infections, it has the highest mortality rate. This study aimed to assess 30-day and overall mortality in invasive candidiasis and candidemia patients depending on the antifungal therapy (AFT) regimens. Materials and Methods:This single-center retrospective study of 30-day survival was conducted at Clinical City Hospital No. 52, Moscow Healthcare Department in Moscow, Russia. The participants were 169 patients aged 19-94 years who had verified invasive candidiasis with candidemia during hospitalization in 2020-2023. This study included patients with Candida spp. isolated from blood culture using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry, and proven invasive candidiasis according to EORTC/MSG criteria. Patient survival analysis was performed using the Kaplan-Meier method, which is a nonparametric approach for estimating time- to-event. Risk of death was compared between the group of patients receiving AFT after pathogen verification and the group of patients receiving AFT before and after blood culture results. Results:Based on the findings, the likelihood of death was lower in the group of patients who received AFT both after and before blood culture results compared to the group of patients who received it after verification of the diagnosis. By day 50 of hospitalization, the risks of death were comparable between the two groups. However, when analyzing the overall mortality, the odds of death in patients with AFT before and after receiving blood culture results were 2.56 times higher (OR=0.391; 95% CI: 0.177-0.865; p=0.019) compared with patients to whom antifungal therapy was prescribed only after blood culture results. Conclusion:This study provided the first data regarding the assessment of 30-day mortality and risk factors for death. Risk of 30-day mortality was lower in the group of patients receiving AFT both before and after the blood culture, but overall mortality in this group was higher, compared to patients who received AFT after the blood culture.
