Candida Parapsilosis Research Articles

Antifungal susceptibility testing and determination of local epidemiological cut-off values for Candida species isolated from women with vulvovaginal candidiasis.

The lack of clinical breakpoints and epidemiological cut-off values (ECOFFs) for antifungals prescribed for vulvovaginal candidiasis (VVC) make interpretation of antifungal susceptibility data difficult. This leads to empirical prescribing, poor clinical management and emergence of resistance. The in vitro susceptibilities of 152 Candida albicans, 105 Candida parapsilosis, 31 Nakaseomyces glabratus, and 8 Pichia kudriavzevii VVC isolates against eight antifungals, were determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.4. The minimum inhibitory concentration (MIC) distributions were analyzed and local ECOFFs were determined visually and statistically. The in vitro activity of azoles was correlated with fluconazole susceptibility and clinical data were evaluated. The MICs of various azoles showed a significant correlation with the MICs of fluconazole and fluconazole non-wild type (WT) isolates had significantly higher MICs for other azoles. The estimated local ECOFFs for C. albicans were 0.016 mg/L (ketoconazole, clotrimazole), 0.06 mg/L (miconazole, econazole, itraconazole), 1 mg/L (fenticonazole), and 3,200 mg/L (boric acid). For C. parapsilosis, local ECOFFs were 0.06 mg/L (ketoconazole, clotrimazole, itraconazole), 1 mg/L (miconazole, econazole), 2 mg/L (fenticonazole), and 3,200 mg/L (boric acid). For N. glabratus, they were 1 mg/L (ketoconazole, clotrimazole, miconazole, itraconazole), 2 mg/L (econazole, fenticonazole), and 12,800 mg/L (boric acid). Non-WT isolates were detected for azoles in N. glabratus (10%-35%), C. albicans (5%-16%), and C. parapsilosis (≤ 3%). All isolates were WT for boric acid. Local ECOFFs were established for three major Candida species causing VVC, guiding the identification of non-WT isolates potentially associated with treatment failure.IMPORTANCEThe interpretation of in vitro susceptibility data of Candida isolates from women with vulvovaginal candidiasis (VVC) is challenging due to the lack of clinical breakpoints (CBPs) and epidemiological cut-off values (ECOFFs) for drugs used in VVC. In the present study, local ECOFFs were established for three major Candida species causing VVC, guiding the identification of non-wild type isolates potentially associated with treatment failure. This paper provides the framework for developing ECOFFs and ultimately CBPs that would help guide antifungal therapy of VVC.

Anidulafungin is a useful surrogate marker for predicting in vitro susceptibility to rezafungin among five Candida species using CLSI methods and interpretive criteria.

This study addresses the use of other echinocandins as surrogate markers to predict the susceptibility of rezafungin against the six most common Candida spp. The Clinical Laboratory Standards Institute (CLSI) reference broth microdilution method was performed to test 5,720 clinical isolates of six different Candida species. Species-specific interpretative criteria by CLSI breakpoints or epidemiological cutoff values were applied. Essential agreement was 100% within two doubling dilutions for all species and comparisons. The categorical agreement of rezafungin using anidulafungin against all Candida spp. was 97.6% (2.9% very major errors [VMEs], 0.2% major errors [MEs], and 2.2% minor errors [miEs]); for caspofungin, it was 99.6% (11.4% VME, 0.09% ME, and 0.19% miE); and for micafungin, it was 99.6% (14.3% VME, 0.15% ME, and 0.17% miE). There were species-specific differences that led to unacceptably high VME for Candida dubliniensis with all agents and for Candida parapsilosis when caspofungin or micafungin but not anidulafungin was used as the comparator. Genetic analysis showed rezafungin nonsusceptibility correlated well with FKS hotspot mutations. The best-performing surrogate was anidulafungin, which can be used to predict rezafungin susceptible or nonsusceptible in Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei with low error rates and ≥90% essential and categorical agreement. Micafungin or caspofungin can also be used as a surrogate marker for predicting rezafungin susceptible or nonsusceptible in C. albicans, C. glabrata, C. tropicalis, and C. krusei. No surrogate performs appropriately to determine rezafungin susceptibility for C. dubliniensis.

Synthesis and evaluation of the antifungal and antibiofilm potential of aminochalcones.

Candida is a commensal fungus of clinical interest that commonly lives in oral cavity and intestine but can become an opportunist microrganism and cause severe infections. A serie of 10 aminochalcones were designed and synthetized to obtain compounds anti-Candida with potent and broad-spectrum activity. The most active compound J34 demonstrated excellent in vitro activity against Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata and Candida krusei with minimum inhibitory concentration between 1.9 and 7.8µg/mL. The association of aminochalcone J34 with amphotericin B demonstrated synergistic effect against C. albicans, with Fractional Inhibiroty Concentration Index (FICI) value of 0.5. Subinhibitory concentration of J34 inhibited the C. albicans adhesion to human keratinocytes. Treatment with J34 reduced C. albicans biofilm formation, as well as acts on preformed biofilm in concentration-dependent mode. Time-kill curve demonstrated that J34 had fungicidal action after 12h of treatment. Preliminary mechanism of action study showed J34 interacts with membrane ergosterol but does not act on fungal cell wall of C. albicans. In additon, in vivo studies using Galleria mellonella indicated low toxic effect of chalcone J34 after 72h of treatment.

Effect of Finger Socks on Clinical Cure in Interdigital Tinea Pedis.

Humidity between the toes and occlusion are risk factors and causes of recurrence for interdigital tinea pedis. To determine the role of wearing "finger-socks" in addition to topical antifungal treatment in managing interdigital tinea pedis. Among 54 patients with interdigital tinea pedis confirmed by direct microscopy, 31 in the study group were recommended to wear five-finger socks in addition to topical antifungal treatment for four weeks, while 23 in the control group received only topical antifungal treatment without sock recommendations. Pre-treatment culture positivity rate was 20.4%, whereas post-treatment, all cases had negative culture results. The most commonly detected microorganisms were Trichophyton rubrum and Candida parapsilosis. In the finger-socks group, the rates of complete cure, partial cure, and treatment failure were 74.2%, 16.1%, and 9.7%, respectively, while 21.7%, 26.1%, and 52.2% in the control group (p<0.001). The small sample size and the high rate of false-negative fungal culture results were our limitations. The clinical complete cure rate was significantly higher in those who wore five-finger socks compared to those who did not. Finger socks increase treatment success in interdigital tinea pedis, presumably by reducing the humidity between the toes, independently of daily habits.

Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.

We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat Candida parapsilosis. High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against C. parapsilosis. This work demonstrates the utility of combining advanced RNA screening methodologies with medicinal chemistry pipelines to identify high-affinity ligands targeting RNA tertiary structures with important roles in human health and disease.

Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study.

This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI). A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included. Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year; 95% confidence interval [CI], 1.01-1.05; P = .0005), solid tumor (aHR 1.91; 95% CI, 1.06-3.46; P = .0302), previous antifungal treatment (aHR 1.84; 95% CI, 1.12-3.10; P = .0192), and septic shock (aHR 2.39; 95% CI, 1.42-4.06; P = .0010), but not fluconazole resistance (aHR 1.00; 95% CI, .62-1.63; P = .9864) nor the type of initial antifungal therapy (aHR 1.46; 95% CI, .69-3.06; P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81; 95% CI, .37-1.75; P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37; 95% CI, 2.11-25.80; P = .0018). Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.

The Relationship Between the Positive Drain Tip Cultures and the Incidence of Surgical Site Infection After Pediatric Cardiovascular Surgery.

Surgical site infection (SSI) is a significant complication following pediatric cardiovascular surgery. Although drain tip cultures (DTC) are sometimes used postoperatively to predict SSIs, their diagnostic value in pediatric cardiovascular surgery remains unclear. This study aimed to assess the diagnostic utility of DTC for predicting SSIs in pediatric cardiovascular surgery patients. This retrospective, single-center cohort study was conducted at a tertiary children's hospital in Japan. We analyzed DTC and SSI data from pediatric patients who underwent cardiovascular surgery between December 2014 and August 2018. Demographic and clinical information was collected, and the incidence of SSIs was compared between patients with positive and negative DTC results. A total of 555 samples from 254 patients were analyzed. DTC was positive in 70 samples (12.6%), and 27 patients (10.6%) had at least 1 positive DTC. The most frequently isolated organism was Staphylococcus epidermidis (n = 44), followed by Candida parapsilosis (n = 8), Staphylococcus lugdunensis (n = 4) and Staphylococcus aureus (n = 3). Twenty patients (7.9%) developed SSIs. The SSI rate was not significantly higher in patients with positive DTC compared with those with negative DTC (14.8% vs. 6.6%, P = 0.13). Only 2 cases showed concordance between the organisms detected in DTC and those responsible for SSIs. The study found that positive DTC was not significantly associated with SSI occurrence after pediatric cardiovascular surgery. Therefore, routine culture of drainage tube tips may not be necessary unless there are clinical signs of infection. Further research is needed to evaluate the role of DTC in specific high-risk scenarios.

Antibacterial and Antifungal Activities of Linear and Cyclic Peptides Containing Arginine, Tryptophan, and Diphenylalanine.

Background. We have previously reported peptides composed of sequential arginine (R) residues paired with tryptophan (W) or 3,3-diphenyl-L-alanine residues (Dip), such as cyclic peptides [R4W4] and [R4(Dip)3], as antibacterial agents. Results. Herein, we report antibacterial and antifungal activities of five linear peptides, namely ((DipR)4(WR)), ((DipR)3(WR)2), ((DipR)2(WR)3), ((DipR)(WR)4), and (DipR)4R, and five cyclic peptides [(DipR)4(WR)], [(DipR)3(WR)2], [(DipR)2(WR)3], [(DipR)(WR)4], and [DipR]5, containing alternate positively charged R and hydrophobic W and Dip residues against fungal, Gram-positive, and Gram-negative bacterial pathogens. The minimum inhibitory concentrations (MICs) of all peptides were determined by the micro-broth dilution method against Methicillin-Resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus subtilis. Fungal organisms were Candida albicans, Candida parapsilosis, and Aspergillus fumigatus. [DipR]5 and ((DipR)2(WR)3) showed MIC values of 0.39-25 µM and 0.78-12.5 µM against Gram-positive and Gram-negative bacteria strains, respectively. The highest activity was observed against S. pneumoniae with MIC values of 0.39-0.78 µM among tested compounds. [DipR]5 demonstrated MIC values of 6.6 µM against C. parapsilosis and 1.6 µM against A. fumigatus, whereas fluconazole showed MIC values of 3.3 µM and >209 µM, respectively. Conclusions. These findings highlight the potential of these peptides as broad-spectrum antimicrobial agents.

Response surface methodology and repeated-batch fermentation strategies for enhancing lipid production from marine oleaginous Candida parapsilosis Y19 using orange peel waste

Oleaginous yeasts are considered promising sources for lipid production due to their ability to accumulate high levels of lipids under appropriate growth conditions. The current study aimed to isolate and identify oleaginous yeasts having superior ability to accumulate high quantities of lipids; and enhancing lipid production using response surface methodology and repeated-batch fermentation. Results revealed that, twenty marine oleaginous yeasts were isolated, and the most potent lipid producer isolate was Candida parapsilosis Y19 according to qualitative screening test using Nile-red dye. Orange peels was used as substrate where C. parapsilosis Y19 produced 1.14 g/l lipids at 23.0% in batch fermentation. To enhance the lipid production, statistical optimization using Taguchi design through Response surface methodology was carried out. Total lipids were increased to 2.46 g/l and lipid content increased to 30.7% under optimal conditions of: orange peel 75 g/l, peptone 7 g/l, yeast extract 5 g/l, inoculum size 2% (v/v), pH 5 and incubation period 6 d. Furthermore, repeated-batch fermentation of C. parapsilosis Y19 enhanced lipid production where total lipids increased at 4.19 folds (4.78 g/l) compared to batch culture (before optimization). Also, the lipid content was increased at 1.7 folds (39.1%) compared to batch culture (before optimization). Fatty acid profile of the produced lipid using repeated-batch fermentation includes unsaturated fatty acids (USFAs) at 74.8% and saturated fatty acids (SFAs) at 25.1%. Additionally, in repeated-batch fermentation, the major fatty acid was oleic acid at 45.0%; followed by linoleic acid at 26.0%. In conclusion, C. parapsilosis Y19 is considered a promising strain for lipid production. Also, both statistical optimizations using RSM and repeated-batch fermentation are efficient methods for lipid production from C. parapsilosis Y19.

Fungal Endocarditis in Pregnancy: A Rare and Fatal Clinical Challenge

Fungal endocarditis is a rare condition whose incidence is increasing due to the rising prevalence of immunocompromised patients, particularly those with HIV. Its occurrence during pregnancy is exceptionally uncommon, presenting unique diagnostic and therapeutic challenges. We report the case of a 33-year-old pregnant woman diagnosed with fungal endocarditis caused by Candida parapsilosis. Despite antifungal treatment and urgent surgical intervention, the outcome was fatal. This case highlights the need for early diagnosis and multidisciplinary management in such complex scenarios.

Rapid Identification of Clinically Relevant Candida spp. by I-dOne Software Using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy.

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy is a spectrum-based technique that quantifies the absorption of infrared light by molecules present in the microbial cell. The aim of the present study was to evaluate the performance of the ATR-FTIR spectroscopic technique via I-dOne software (Version 2.0) compared with the MALDI-TOF MS in identifying Candida spp. Each infrared spectrum was compared with spectra stored in the software database. The updated version of the I-dOne software was used to analyze ATR-FTIR spectra. All Candida isolates 284/284 (100%) were classified correctly according to the genus. Overall species identification yielded 272/284 (95.8%) concordant identification results with MALDI-TOF MS. Additionally, all 79 isolates belonging to the Candida parapsilosis species complex were identified correctly to the species level with the updated version of the I-dOne software. Only 12 (4.2%) isolates were misidentified at the species level. The present study highlights the potential diagnostic performance of the I-dOne software with ATR-FTIR spectroscopic technique referral spectral database as a real alternative for routine identification of the most frequently isolated Candida spp.

CHEMICAL CONSTITUENTS, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF Pavonia glazioviana Gurke (Malvaceae)

Species from Pavonia genus (Malvaceae) are traditionally used as antioxidant, n‑anti‑inflammatory and antimicrobial remedies. Previous studies have revealed their diversity of specialized metabolites widely used in the development of new medicines. This is the first study on Pavonia glazioviana Gurke, a Brazilian species known as “Malva‑da‑Chapada”. The research led to identify fifteen compounds: 132‑(S)‑hydroxy‑pheophytin a; and 132(S)‑hydroxy‑173‑ethoxyphaeophorbide, n‑decanol, cycloart‑23Z‑ene‑3β,25‑diol, cycloart‑24S‑25‑ene‑3β,24‑diol, sitosterol‑3‑O‑β‑D‑glucopyranoside, stigmasterol‑3‑O‑β‑D‑glucopyr anoside, quercetin, acacetin, kaempferol, tiliroside, 5‑hydroxy‑3,7,8,4’‑tetramethoxyflavone, 5,7‑dihydroxy‑3,8,4’‑trimethoxyflavone, 5,7‑dihydroxy‑4’‑methoxyflavone, 5,7,4’‑trihydroxy‑3,8‑dimethoxyflavone and 5,7,4’‑trihydroxy‑3‑methoxyflavone. The major flavonoids were tested for their antimicrobial activity, and the compound 5,7‑dihydroxy‑3,8,4’‑trimethoxyflavone showed strong activity against Escherichia coli (MIC = 512 μg mL‑1), Pseudomonas aeruginosa (MIC = 512 μg mL‑1), Candida albicans (MIC = 512 μg mL‑1), Candida tropicalis (MIC = 512 μg mL‑1), Candida parapsilosis (MIC = 512 μg mL‑1), Aspergillus flavus (MIC = 512 μg mL‑1) and A. fumigantus (MIC = 512 μg mL‑1). The total phenolic content, flavonoid content, and radical scavenging potential were determined showing its great production of phenolics and flavonoids, along with interesting radical scavenging potential (DPPH EC50 = 6.36 ± 0.029 mg mL‑1). Our findings contributed to characterize P. glazioviana as a source of methoxylated flavonoids with antimicrobial potential.

Inter-Institutional Dynamics and Impact of Fluconazole-Resistant Candida parapsilosis.

Infections with fluconazole-resistant Candida parapsilosis have been increasing in Israeli hospitals with unclear implications for patient outcomes. To determine the frequency, mechanisms, molecular epidemiology, and outcomes of azole-resistant C. parapsilosis bloodstream infections in four hospitals in Israel. C. parapsilosis bloodstream isolates were collected at four hospitals in central Israel during varying periods from 2005 to 2022. Antifungal susceptibility testing was done using CLSI broth microdilution. Risk factors for fluconazole resistance were investigated using logistic regression. ERG11 gene sequencing was performed on all isolates. Genetic relatedness was determined using multilocus microsatellite genotyping. Clinical cure, microbiological eradication, and mortality rates were compared between fluconazole-susceptible and resistant isolates. A total of 192 patient-specific C. parapsilosis isolates were analysed. Resistance to fluconazole and voriconazole was detected in 80 (41%) and 14 (7.2%) isolates, respectively. The ERG11 Y132F substitution was found in 91% of fluconazole-resistant and 1% of fluconazole-susceptible isolates. Increasing age, intensive care hospitalisation, haemodialysis, and recent exposure to antibiotics were risk factors for fluconazole-resistant C. parapsilosis. Distinct but related genotypes predominated at each centre, indicating extensive dissemination within hospitals and limited transmission among them. Fluconazole resistance was associated with increased likelihood of microbiological failure but no significant difference in clinical cure and mortality. We found high rates of fluconazole resistance in C. parapsilosis, attributable to nosocomial spread of hospital-specific clones bearing the Y132F substitution. Fluconazole resistance was associated with a higher risk of microbiological but not clinical failure. Strategies to limit nosocomial transmission of C. parapsilosis are needed.

Epidemiology of Vulvovaginal Candidiasis in Greece: A 2-Year Single-Centre Study.

The epidemiology of vulvovaginal candidiasis (VVC) in Greece remains poorly reported and outdated. We therefore conducted a 2-year retrospective survey to assess the epidemiological aspects of the infection among symptomatic Greek patients. High vaginal swab samples were collected from adult women with clinically suspected VVC attending a private diagnostic laboratory in Athens. VVC was confirmed through microscopic examination of a wet mount preparation revealing yeasts and Candida-positive culture. Species were identified by MALDI-ToF MS, and invitro susceptibility was determined according to the EUCAST-E.Def 7.4. Predisposing host factors were associated with the occurrence of the infection and isolated Candida spp. using Fisher's exact test, and epidemiological changes over time were analysed with the χ2 test for trend. Among 1300 women screened, 283 VVC episodes were recorded among 233 (18%) patients, whereof 11 (5%) had recurrent VVC (RVVC) and 19 (8%) had mixed Candida infections. Coinfection with other pathogens and recent prior use of antifungals were associated with RVVC. Candida albicans was the most prevalent pathogen (50%), followed by Candida parapsilosis sensu stricto (SS) (35%), Nakaseomyces glabratus (former Candida glabrata) (10%), Pichia kudriavzevii (former Candida krusei) (3%), Candida orthopsilosis (1.5%) and Clavispora lusitaniae (former Candida lusitaniae) (0.5%). Regarding the RVVC cases, 54% were attributed to C. albicans, 37% to N. glabratus and 9% to C. parapsilosis SS. Resistance to fluconazole was found in 4% of C. albicans and 23% of N. glabratus strains with cross-resistance to other azoles. Fluconazole-resistant isolates were recovered from 5 of 11 RVVC patients, whereof 4 of 5 had previous exposure to azoles. During the study period, an increase in N. glabratus VVC and fluconazole resistance was noted. VVC is common in our region, with C. albicans as the predominant species, followed by C. parapsilosis SS and N. glabratus. Fluconazole resistance is low in C. albicans but high in N. glabratus, emphasising the need for targeted antifungal strategies.

Molecular Detection of Virulence Factor Genes in Candida parapsilosis Isolated from Subclinical Mastitis Goats and Antifungal Susceptibility in Mosul Province

Molecular Detection of Virulence Factor Genes in Candida parapsilosis Isolated from Subclinical Mastitis Goats and Antifungal Susceptibility in Mosul Province

Candidemia chronicles: Retrospective analysis of candidemia epidemiology, species distribution, and antifungal susceptibility patterns in Bahrain.

Invasive fungal infections, particularly candidemia, pose significant clinical challenges globally. Understanding local epidemiology, species distribution, and antifungal susceptibility patterns is crucial for effective management despite regional variations. To investigate the epidemiology, species distribution, antifungal susceptibility patterns, and associated risk factors of candidemia among patients in Bahrain from 2021 to 2023. This retrospective study analyzed demographic data, Candida species distribution, antifungal susceptibility profiles, and risk factors among candidemia patients treated at a tertiary care hospital in Bahrain over three years. Data was collected from medical records and analyzed using descriptive statistics. A total of 430 candidemia cases were identified. The mean age of patients was 65.7 years, with a mortality rate of 85.5%. Candida albicans (C. albicans) was the most common species, followed by Candida parapsilosis, Candida tropicalis (C. tropicalis), and emerging multidrug-resistant Candida auris (C. auris). Antifungal susceptibility varied across species, with declining susceptibility to azoles observed, particularly among C. albicans and C. tropicalis. Major risk factors included central venous catheters, broad-spectrum antibiotics, and surgical procedures. This study highlights the substantial burden of candidemia among older adults in Bahrain, characterized by diverse Candida species. It also concerns levels of antifungal resistance, notably in C. auris. The findings underscore the importance of local epidemiological surveillance and tailored treatment strategies to improve outcomes and mitigate the spread of multidrug-resistant Candida species. Future research should focus on molecular resistance mechanisms and optimizing therapeutic approaches to address this growing public health concern.

Purification, Characterization, and Antimicrobial Activity Against Candida parapsilosis and Staphylococcus aureus of a Highly Stable Type-1 Cystatin from Terminalia catappa L. Seeds.

Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant. The current study purified, characterized, and assessed the antimicrobial activity of a papain inhibitor from Terminalia catappa L. seeds. The inhibitor was purified by heating the crude extract at 80°C for 30 min, followed by ion exchange chromatography on a DEAE cellulose column. The purification index was 9-fold, yielding 2.3%. SDS-PAGE and size exclusion chromatography revealed that the protease inhibitor (TcPI) is a 15.9 kDa monomeric protein. The inhibition kinetics showed that TcPI is a competitive inhibitor specific to papain (Ki = 1.02 x 10-4 M). TcPI remained active even after heating at 100 ºC for 120 min and at pH conditions varying from 2.0 to 10.0. Even after 60 min, TcPI was resistant to papain proteolysis. TcPI exhibited antimicrobial activity against Candida parapsilosis and Staphylococcus aureus. Here, we show that TcPI is a highly stable type-1 cystatin with the potential to combat infections caused by C. parapsilosis and S. aureus. Additional investigations into TcPI's structural aspects and mechanism of action, as well as safety assessments, are essential prerequisites for its potential application as a novel therapeutic intervention.

Population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation-an ASAP ECMO study.

This study aimed to describe the population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) and to identify dosing regimens with a high likelihood of achieving effective exposures. Serial blood samples were collected over a single-dosing interval during ECMO. Total plasma concentrations were measured by a validated chromatographic assay. A population pharmacokinetic model was built and Monte Carlo dosing simulations were performed using Monolix. The probability of target attainment (PTA) and fractional target attainment (FTA) rates were simulated for various caspofungin dosing regimens against Candida albicans, Candida glabrata, and Candida parapsilosis. In all, 64 plasma concentration-time points were obtained from 8 critically ill patients receiving ECMO. Plasma concentration-time data for caspofungin were best described by a one-compartment model with first-order elimination. Lean body weight was identified as a significant covariate of volume of distribution. The typical volume of distribution and clearance of caspofungin in this cohort were 8.13 L and 0.55 L/h, respectively. The licensed caspofungin dosing regimen (a loading dose of 70 mg on day 1 followed by a maintenance dose of either 50 mg/day or 70 mg/day) demonstrated optimal PTA rates (≥90%) against C. albicans with an MIC of ≤0.064 mg/L, C. glabrata with an MIC of ≤0.125 mg/L, and C. parapsilosis with an MIC of ≤0.064 mg/L. The FTA analysis suggested that the licensed dosing regimen is only optimal (≥95%) against Candida glabrata, regardless of lean body weight. A higher-than-standard empirical dosing regimen (e.g., a loading dose of 100 mg on day 1, followed by a maintenance dose of 100 mg daily) is likely advantageous for critically ill patients receiving ECMO.

Chemometrics of the Seasonal Influence on Chemical Composition, Yield, Antioxidant Capacity, and Anti-Candida Activity of Alpinia nutans Essential Oil Growing in the Brazilian Amazon Region.

Alpinia nutans (L.) Roscoe (Zingiberaceae) is used in folk medicine as an antiviral, anti-inflammatory, and antioxidant. This study aimed to evaluate the seasonality effects on the yield, chemical composition, antioxidant capacity, and anti-Candida activity of the A. nutans essential oil (EO). The specimen was collected monthly for 1 year in Belém, Pará, Brazil. The leaf EOs were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC/MS), and the antioxidant capacity was evaluated by DPPH and β-carotene/linoleic acid. The EO yield showed no significant difference between dry (1.80%±0.29) and rainy (1.75%±0.11) seasons. The main chemical constituents identified in the EOs were terpinen-4-ol (13.93%-23.14%), 1,8-cineole (15.83%-18.43%), and p-cymene (14.41%-20.16%). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) showed three groups with major constituents in different proportions. None of the samples showed significant inhibition in the DPPH and β-carotene/linoleic acid antioxidant method. Analyzing the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), the samples from dry and rainy seasons showed high activity against strains of Candida albicans (MIC 5mg/mL; MFC 10mg/mL), Candida parapsilosis (MIC 2.5mg/mL; MFC 10mg/mL), and Candida tropicalis (MIC 10mg/mL; MFC 10mg/mL). There were only quantitative variations in the chemical composition of A. nutans EO. The anti-Candida potential of the EO was also not influenced by seasonality. The A. nutans EO may be promising to produce anti-Candida phytopharmaceuticals. However, the chemical variability of this species throughout the year should be considered for this purpose.

Atividade antimicrobiana dos extratos hidroalcoólicode Eugenia uniflora L. (Myrtaceae) e Schinus molle L.(Anacardiaceae)

The indiscriminate use of antimicrobials available in the market today has been contributing to the increase in the quantity of resistant pathogens. In recent years, significant attention has been given to the use of antimicrobial compounds of natural origin. This growing demand for new bioactive compounds stems from the knowledge that some medicinal plants often exhibit antimicrobial activity. Thus, the aim of this study was to evaluate the antimicrobial effect of hydroalcoholic extracts from the leaves of E. uniflora (Surinam cherry) and S. molle (Brazilian pepper tree) against clinically relevant microorganisms. The leaves were collected from adult plants, identified at the Herbarium of the University of Vale do Sapucaí, where a voucher specimen was deposited. The extract was prepared using the maceration technique in 70% ethanol. Antimicrobial activity was assessed using the disc diffusion method according to the Kirby-Bauer methodology. The microorganisms used were reference strains of: Escherichia coli ATCC8739, Staphylococcus aureus ATCC6538, Pseudomonas aeruginosa ATCC9027, Salmonella typhimurium ATCC14028, Candida albicans ATCC90028, Candida glabrata MYA2950, Candida Krusei ATCC6258, Candida parapsilosis ATCC22019, and Candida utilis ATCC9950. The extracts showed antifungal and antibacterial activity against the studied microorganisms. These findings contribute to the potential future use of these plants as antimicrobial agents.