Search Results (162)

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

The increasing emergence of antifungal resistance poses potential clinical challenges, particularly among immunocompromised patients with cancer at risk of invasive mold infections, but data on antifungal susceptibility trends specific to this population are few. We evaluated distributions of minimal inhibitory concentrations (MIC), including minimal effective concentrations (MEC) for echinocandins, of 11 antifungal agents for 523 mold isolates (395 Aspergillus spp.) from cancer patients. Based on published Clinical and Laboratory Standards Institute guidelines, isavuconazole had notably high rates of non-wild-type MICs for A. fumigatus (19.6%), A. flavus/oryzae (34.8%), A. niger complex (26.1%), and A. terreus complex (8.33%). Persistent low baseline resistance of A. fumigatus to voriconazole was observed across multiple years (2.4–11.5% per year, average 8.41%) without significant trends in MIC change over time. Itraconazole and posaconazole demonstrated the lowest MIC distributions (MIC₅₀ ≤ 0.06–0.5 µg/mL) of the azoles against Aspergillus spp. Amongst the A. niger complex, 29.4% (27/92) demonstrated non-wild-type MICs to itraconazole. While the A. nidulans group was less frequent (n = 24), bimodal peaks in MIC/MEC were noted for caspofungin (≤0.06 and 1 µg/mL). Non-Aspergillus molds of significance (Zygomycetes, Fusarium spp., Scedosporium spp., and Lomentospora prolificans) demonstrated variable but increased MICs to antifungal agents as previously described. Our results highlight increased rates of non-wild type MICs for Aspergillus spp. to isavuconazole and voriconazole, which are commonly used antifungal agents in cancer patients. Such AST trends should be closely monitored in populations with frequent antifungal use and encourage increased antifungal stewardship efforts. Full article

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021–2025). Patients received either caspofungin or posaconazole as PAP based on the drug–drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies. Full article

With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels. Full article

Candida glabrata is an opportunistic, pathogenic fungus that is increasingly isolated from hospitalized patients. The incidence of drug tolerance, heteroresistance, and resistance is on the rise due to an overuse of antifungal drugs. The aim of this study was to expose a sensitive C. glabrata strain to sequentially increasing concentrations of two antifungal drugs, fluconazole, an azole that targets ergosterol biosynthesis, or caspofungin, an echinocandin that targets cell wall glucan synthesis. Analysis of the drug-exposed isolates showed development of antifungal tolerance, chromosomal abnormalities, decreased adhesion, attenuated virulence, and an increase in efflux pump activity. Furthermore, whole genome sequencing of all isolates exposed to different concentrations of fluconazole or caspofungin was performed to determine mutations in key genes that could correlate with the observed phenotypes. Mutations were found in genes implicated in adhesion, such as in the AWP, PWP, and EPA family of genes. Isolates exposed to higher drug concentrations displayed more mutations than those at lower concentrations. Full article

Candida infective endocarditis presents therapeutic challenges with high mortality. A complex case of Candida prosthetic valve endocarditis refractory to standard antifungals (anidulafungin and fluconazole) and high-dose caspofungin was successfully treated with heart transplantation. The literature review revealed a few cases of bacterial endocarditis successfully treated with heart transplantation, but with only two transplanted cases of fungal endocarditis. This report explores heart transplantation as a last resort for managing refractory infective endocarditis. The patient is still alive and free of infection, two and a half years after transplantation. Full article

Moesziomyces spp. (Pseudozyma) is a genus recognized as a new opportunistic human pathogen, causing systemic infections including premature neonates and adult patients. These fungi’s natural resistance to caspofungin enables them to spread through vascular catheter colonization, making them a new etiological agent associated with fungal bloodstream infections (FBIs) and a significant contributor to high mortality rates. In this report, we present a case of fungemia caused by Moesziomyces aphidis species in a patient with medical history that revealed pancreatic cancer infiltrating the duodenum and bile ducts. During hospitalization, the M. aphidis was cultured twice from peripheral blood samples on Sabouraud agar. The strain was sensitive to amphotericin B and voriconazole. In vitro susceptibility testing revealed resistance to fluconazole, caspofungin, anidulafungin, and micafungin. Antifungal therapy with voriconazole resulted in the resolution of clinical symptoms associated with fungal infection. Related to M. aphidis fungemia, we reviewed a total of three cases in Europe published in the PubMed database between 2003 and 2024. To the best of our knowledge, this is the first case of M. aphidis FBI in Poland and the fourth case in an adult patient in Europe. Full article

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. Full article

Fungi are a typical part of the microbiome of poultry houses, but some of the genera can be pathogenic for poultry and humans. An investigation was conducted on 200 duck eggs from 10 flocks to determine total fungal contamination on the eggshells. The colony types were identified morphologically and microscopically, and a representative group was identified using PCR. The resistance profiles for all obtained Aspergillus isolates were conducted. The dominating genera on eggshells were Penicillium, Alternaria and Aspergillus and the number of fungal colonies ranged from 0 to 7100. Aspergillus fumigatus was cultured from 9.5% eggshells, and all isolates were obtained from three flocks. The minimum inhibitory concentration (MIC) values for A. fumigatus isolates ranged from 0.094–32 μg/mL for amphotericin B (MIC 50 1 mg/L and MIC 90 32 μg/mL), 0.125–32 μg/mL for caspofungin (MIC 50 0.38 μg/mL and MIC 90 32 μg/mL), 0.19–32 μg/mL for itraconazole (MIC 50 1.5 μg/mL and MIC 90 32 μg/mL), 0.047–12 μg/mL for posaconazole (MIC 50 0.5 μg/mL and MIC 90 8 μg/mL) and 0.023–32 μg/mL for voriconazole (MIC 50 0.19 μg/mL and MIC 90 32 μg/mL). A total of 73.7% of the isolates were resistant to posaconazole and 68.4% to itraconazole. Nearly half of the strains (47.4%) showed resistance to amphotericin B and 31.6% to voriconazole. Because of the lack of antifungals registered for poultry, hygiene and the regular disinfection of litter in particular are needed to prevent the contamination of the eggs by fungi for both animal and human health. Full article

Aspergillus fumigatus (A. fumigatus) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchange factor Sec2p gene led to slower A. fumigatus growth and reduced the fungal burden and mortality of infected mice. However, the mechanism by which this gene affects A. fumigatus growth and pathogenicity remains unclear. Transmission electron microscopy revealed that the vacuoles of the gene knockout strain ΔSec2p accumulated more autophagosomes, indicating inhibition of autophagosome degradation. When phenylmethylsulfonyl fluoride was applied to inhibit autophagosome degradation, the ΔSec2p strain produced fewer autophagosomes; the ΔSec2p autophagy pathway was inhibited, affecting A. fumigatus’ nutrient homeostasis and growth. Unlike the wild type, the ΔSec2p strain showed strong resistance to cell wall stress. When exposed to caspofungin, Sec2p negatively regulated the expression of cell wall integrity (CWI) pathway genes and participated in the cell wall stress response of A. fumigatus. Furthermore, this gene positively regulated the autophagy pathway and enhanced CWI pathway gene expression to respond to rapamycin-induced autophagy. In summary, Sec2p positively regulated the autophagy pathway; it negatively regulated the CWI pathway during cell wall stress, coordinating the growth and pathogenicity of A. fumigatus. Full article

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile. Full article

Today, Candida albicans is still the most common cause of both local and life-threatening systemic candidiasis. The spread of resistant fungal strains has resulted in an urgent need to search for new promising antimycotics. Here, we investigated the antifungal action of the tobacco defensin NaD1 against susceptible and resistant to azoles and echinocandins strains of C. albicans. We demonstrated that NaD1 was equally effective and fungicidal against all tested strains. The MIC and MFC values were 6.25 and 12.5 µM, respectively. We showed for the first time that NaD1 could act synergistically not only with caspofungin but also with human host defense antimicrobial peptides cathelicidin LL-37 and β-defensin-2 (HBD2) against susceptible and resistant fungal strains. Using flow cytometry, we demonstrated that NaD1 in combinations with LL-37 or HBD2 can reinforce each other by enhancing membrane disruption. Using the Caco-2 cell monolayer model, we demonstrated that NaD1 impaired the adhesion of C. albicans cells to the human epithelium. Moreover, NaD1 inhibited the formation of fungal biofilms in Sabouraud broth and less markedly in nutrient-rich RPMI-1640 medium, and enhanced the antibiofilm activity of caspofungin. Thus, we hypothesized that NaD1 might affect the development of candidiasis in vivo, including that caused by resistant fungal strains. Full article

The synthesis of tetra- and pentanorlabdane compounds with rearranged cycle B based on commercially available (+)-sclareolide is reported. Desired compounds were prepared from intermediate ketones via Baeyer–Villiger oxidation. The structures of synthesized compounds were confirmed by spectral IR, 1D (¹H, ¹³C, and DEPT), and 2D (H-COSY, H,C-HSQC, H,C-HMBC, H,N-HMBC, NOESY) NMR analyses, mass-spectrometry and single crystal X-rays diffraction. Two out of the four synthesized compounds showed high antifungal and antibacterial activities comparable to and exceeding standard antifungal (caspofungin) and antibacterial (kanamycin) agents. DFT calculations show that in gas and DCM, compound 4 is more stable than 3 with a difference in the Gibbs free energy of 23.3 kJ/mol and 20.7 kJ/mol, respectively. In water and methanol, compound 3 is slightly more stable, by 2.4 kJ/mol and 2.78 kJ/mol, respectively. Molecular docking to four targets DNA gyrase from E. coli (1KZN), Fabz from P. aeruginosa (1U1Z), dihydrofolate reductase from C. albicans (3QLS) and MurB from E. coli (2Q85) showed good agreement with the results of in vitro evaluation and confirmed the biological activity of compounds 3 and 4, with binding affinities comparable and for some targets exceeding that of Caspofungin and Kanamycin. Full article

In this study, metagenomic analysis was employed to investigate the bacterial communities in the Muan tidal mudflat of the Republic of Korea. We used metagenomic analysis to identify the microbial community in tidal soil dominated by Proteobacteria. From this environment, the bacterial strain, Saccharomonospora sp. CMS18, was isolated and yielded two previously unknown compounds, penipaline D (3) and N-acetyl-dimethylallyltryptophan (4). The chemical structures of the isolated compounds along with 6-dimethylallyl-indole (1), 6-dimethylallyltryptophan (2), penipaline D (3), and N-acetyl-dimethylallyltryptophan (4) were structurally investigated using HR-ESI-MS and NMR spectroscopy. The isolated compound 6-dimethylallyl-indole (1) demonstrated broad-spectrum antifungal activity, with IC₅₀ value of 0.04 mM against Candida glabrata and 0.35 mM against both Candida albicans and Cryptococcus neoformans. Additionally, it exhibited additive interaction with caspofungin against C. albicans. Full article

Nakaseomyces glabrata (Candida glabrata), the second most prevalent Candida pathogen globally, has emerged as a major clinical threat due to its ability to develop high-level azole resistance. In this study, two new 5,6-dihydrotetrazolo[1,5-c]quinazoline derivatives (c11 and c12) were synthesized and characterized using IR, LC-MS, ¹H, and ¹³C NMR spectra. Along with 13 previously reported analogues, these compounds underwent in vitro antifungal testing against clinical N. glabrata isolates using a serial dilution method (0.125–64 mg/L). Remarkably, compounds c5 and c1 exhibited potent antifungal activity, with minimum inhibitory concentrations of 0.37 μM and 0.47 μM, respectively—about a 20-fold improvement in μM concentration over standard drugs like amphotericin B, caspofungin, and micafungin. A detailed structure–activity relationship analysis revealed crucial molecular features enhancing antifungal potency. Extensive molecular docking studies across 18 protein targets explored potential binding pockets and affinities of the lead compounds. A robust 3D-QSAR model, incorporating molecular descriptors Mor26m and Mor29e, displayed good predictive ability for antifungal activity. In silico predictions indicated an absence of herbicidal effect, negligible environmental toxicity (to honeybees, avian species, and aquatic organisms), and mild human toxicity concerns for these compounds. This comprehensive approach aims to develop novel and effective antifungal compounds against the clinically relevant pathogen N. glabrata. Full article