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ABSTRACT The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C. glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles.IMPORTANCEThe prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy.

Among ultrasound images, the acoustic radiation force impulse (ARFI) image can provide information about the stiffness of the tissue using both a pushing beam and a detection beam. However, there is a problem in that the impulse noise is generated in the process of generating the ARFI image by calculating the displacement of the target. The impulse noise appearing in the ARFI image can be caused by various factors related to ultrasound image processing and the characteristics of the target tissue, and it can degrade image quality and the accuracy of stiffness measurements. The commonly used fixed median filter in the ARFI image can effectively eliminate the impulse noise but may introduce a blurring effect, depending on the kernel size. The adaptive median filter has the advantage of minimizing the impulse noise level while preserving the original information as much as possible, but the adaptive median filter has been generally used to remove the unipolar or bipolar type noise from the image. As a result, the effectiveness of removing the impulse noise with various amplitudes from the ARFI image is not sufficient. To figure out this problem, in this study, we propose the adaptive median filter method combined with probability mass function. In this method, in order to limit the various amplitudes of impulse noise as much as possible, the threshold cut-off level of impulse noise is determined by a probability mass function, and then adaptive median filter is used to effectively remove impulse noise with limited amplitude. The performance of the proposed method was evaluated by using a tissue mimicking phantom and a bovine eye. Therefore, the proposed technique is expected to be one of the useful methods to improve the overall quality and reliability of the ARFI images for clinical diagnosis and evaluation.

ABSTRACT We newly detected two (sinking and floating) phenotypes of Candida parapsilosis among bloodstream infection (BSI) isolates from Korean hospitals and assessed their microbiological and clinical characteristics. During the performance of a Clinical and Laboratory Standards Institute (CLSI) broth microdilution antifungal susceptibility testing, the sinking phenotype had a characteristic smaller button-like appearance because all yeast cells sank to the bottoms of the CLSI U-shaped round-bottom wells, whereas the floating phenotype comprised dispersed cells. Phenotypic analysis, antifungal susceptibility testing, ERG11 sequencing, microsatellite genotyping, and clinical analysis were performed on C. parapsilosis isolates from 197 patients with BSI at a university hospital during 2006 to 2018. The sinking phenotype was detected in 86.7% (65/75) of the fluconazole-nonsusceptible (FNS) isolates, 92.9% (65/70) of the isolates harboring the Y132F ERG11 gene substitution, and 49.7% (98/197) of all isolates. Clonality was more frequently observed for the Y132F-sinking isolates (84.6% [55/65]) than for all other isolates (26.5% [35/132]; P

We analyzed the virulence traits and azole resistance mechanisms of 104 Candida auris isolates collected from 13 Korean hospitals from 1996 to 2022. Of these 104 isolates, 96 (5 blood and 91 ear isolates) belonged to clade II, and 8 (6 blood and 2 other isolates) belonged to clade I. Fluconazole resistance (minimum inhibitory concentration ≥32 mg/L) was observed in 68.8% of clade II and 25.0% of clade I isolates. All 104 isolates were susceptible to amphotericin B and three echinocandins. In 2022, six clade I isolates indicated the first nosocomial C. auris cluster in Korea. Clade II C. auris isolates exhibited reduced thermotolerance at 42 °C, with diminished in vitro competitive growth and lower virulence in the Galleria mellonella model compared to non-clade II isolates. Of the 66 fluconazole-resistant clade II isolates, several amino acid substitutions were identified: Erg11p in 14 (21.2%), Tac1Ap in 2 (3.0%), Tac1Bp in 62 (93.9%), and Tac1Bp F214S in 33 (50.0%). Although there were a limited number of non-clade II isolates studied, our results suggest that clade II C. auris isolates from Korean hospitals might display lower virulence traits than non-clade II isolates, and their primary fluconazole resistance mechanism is linked to Tac1Bp mutations.

Context: Tooth loss exacerbates the deterioration of physical function and induces illness. Numerous studies have identified the risk factors for tooth loss, and several have identified an association of tooth loss with sociodemographic factors, general health status, and lifestyle. Aims: The objective of the present cohort study was to elucidate the relationship between regular dental scaling and tooth loss in middle-aged and elderly individuals in Korea. Settings and Design: The study was 3-year prospective longitudinal study and conducted in Wonju-si of South Korea. Methods: In total, 557 subjects (219 men, 338 women; 40–75 years) were included in our 3-year follow-up survey (2010–2014). Data from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KOGES-ARIRANG) were used. All subjects underwent an oral examination and face-to-face interview for taking oral health behavior, sociodemographic status, and the utilization of dental service. Statistical Analysis Used: Logistic regression analysis was used to determine the effects of regular dental scaling on tooth loss after adjusting for history of oral examinations and dental visits, oral health behavior, and sociodemographic status. Results: In total, 263 subjects (47.2%) experienced a loss of one or more teeth during the 3-year period, and lost a mean of 1.54 ± 2.53 teeth. The incidence of tooth loss was 1.87 (1.03–3.38) times higher in participants who did not undergo dental scaling during the 3-year period than in those who regularly received dental scaling. Conclusions: This study showed the potential causal relationship between tooth loss and regular dental scaling for preventing oral disease. Further study is needed to consolidate the evidence that regular dental scaling is effective in preventing tooth loss.

We incorporated nationwide Candida antifungal surveillance into the Korea Global Antimicrobial Resistance Surveillance System (Kor-GLASS) for bacterial pathogens. We prospectively collected and analyzed complete non-duplicate blood isolates and information from nine sentinel hospitals during 2020–2021, based on GLASS early implementation protocol for the inclusion of Candida species. Candida species ranked fourth among 10,758 target blood pathogens and second among 4050 hospital-origin blood pathogens. Among 766 Candida blood isolates, 87.6% were of hospital origin, and 41.3% occurred in intensive care unit patients. Adults > 60 years of age accounted for 75.7% of cases. Based on species-specific clinical breakpoints, non-susceptibility to fluconazole, voriconazole, caspofungin, micafungin, and anidulafungin was found in 21.1% (154/729), 4.0% (24/596), 0.1% (1/741), 0.0% (0/741), and 0.1% (1/741) of the isolates, respectively. Fluconazole resistance was determined in 0% (0/348), 2.2% (3/135, 1 Erg11 mutant), 5.3% (7/133, 6 Pdr1 mutants), and 5.6% (6/108, 4 Erg11 and 1 Cdr1 mutants) of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis isolates, respectively. An echinocandin-resistant C. glabrata isolate harbored an F659Y mutation in Fks2p. The inclusion of Candida species in the Kor-GLASS system generated well-curated surveillance data and may encourage global Candida surveillance efforts using a harmonized GLASS system.

This study aimed to investigate whether dietary supplementation with heat-inactivated Limosilactobacillus reuteri PSC102 (LR) enhances immunological responses and growth performance in weaned pigs. Twenty-five weaned piglets were randomly allocated to five groups. Each treatment group had separate pens with five pigs each. The pigs were fed a diet supplemented with heat-inactivated LR at a concentration of 1x109 CFU/g for 28 days. Throughout the study period, regular measurements, including body weight, food consumption rate, and diarrhoeal frequency, were conducted. At the end of the experiment, blood samples were collected to assess cytokine and haptoglobin levels. Faecal samples, rectal swabs, and nasal swabs were collected for analysis of pathogenic bacterial growth using selective media. Additionally, faecal samples were analysed to determine the composition of the microbiota. Heat-inactivated LR enhances growth rate and feed efficiency while decreasing diarrheal frequency in weaned piglets. Compared to pigs fed a control diet, diets containing heat-inactivated LR exhibited increased serum levels of cytokines and decreased haptoglobin levels, demonstrating a beneficial effect on the presence of pathogenic microorganisms. Heat-inactivated LR diets alter the microbiota of piglets by enhancing alpha diversity and increasing the composition of beneficial bacteria. Overall, dietary heat-inactivated LR enhanced growth rates, regulated immunological responses in weaned pigs, and reduced post-weaning diarrhoea. Therefore, this suggests its potential as a health functional ingredient for humans and animals. [ABSTRACT FROM AUTHOR]

Abstract Tylosin, an antibiotic with a long history in treating respiratory bacterial infections, has unknown effects on the gut microbiota of healthy and infected pigs. The study aimed to investigate the effect of a therapeutic dose of tylosin on swine gut microbiota and explored the relationship between this effect and tylosin pharmacokinetics (PK). We also assessed whether changes in gut microbiota after tylosin administration differ between healthy animals (n = 7) and animals intranasally co-infected (n = 7) with Actinobacillus pleuropneumoniae and Pasteurella multocida. Both groups were intramuscularly administered with tylosin (20 mg/kg). The 16S rRNA gene analyses revealed a significantly lower species richness and diversity, after tylosin treatment, in the infected than the healthy pigs, with infected pigs having lower levels of Bacteroidetes and Firmicutes and higher levels of Proteobacteria. Greater tylosin exposure (greater area under curve (AUC) and maximum plasma concentration (Cmax), and slower elimination (longer terminal half-life, T1/2) were observed in healthy than infected pigs. Relative abundance of Lactobacillus, Oscillibacter, Prevotella, and Sporobacter was positively and significantly correlated with AUC and Cmax, whereas the abundance of Acinetobacter, Alishewanella, and Pseudomonas was positively and significantly correlated with T1/2 and mean residence time (MRT) of tylosin. Our findings, for the first time, demonstrated significant changes in swine gut microbiota after a single therapeutic dose of tylosin was administered, whereas the effect of these changes on tylosin PK was not evident.

Employing affordable and uncomplicated sample preparation techniques to recommend the most efficient antibacterial therapy could help reduce antibiotic-resistant bacteria. This study evaluated the suitability of immunoassays and microbiological assays as alternatives for liquid chromatography/mass spectrometry (LC/MS) in determining plasma tylosin concentrations after intramuscular administration at a dose of 20 mg/kg to both healthy and diseased pigs in clinical veterinary practice. The diseased pigs were confirmed using the target genes Actinobacillus pleuropneumoniae (apxIVA) and Pasteurella multocida (kmt1). The methods showed good linearity, precision, and accuracy. In both healthy and diseased pigs, a significant correlation was observed between LC/MS and the microbiological assay (Pearson correlation coefficient: 0.930, p < 0.001 vs. Pearson correlation coefficient: 0.950, p < 0.001) and between LC/MS and the enzyme-linked immunosorbent assay (ELISA) (Pearson correlation coefficient: 0.933; p < 0.001 vs. Pearson correlation coefficient: 0.976, p < 0.001). A strong correlation was observed between the microbiological assay and the ELISA in both healthy and diseased pigs (Pearson correlation coefficient: 0.911; p < 0.001 vs. Pearson correlation coefficient: 0.908, p < 0.001). A Bland-Altman analysis revealed good agreement between the methods, i.e., 95% of the differences were within the limits of agreement. Therefore, the microbiological assay and the ELISA, which demonstrated sufficient precision and accuracy, can be viable alternatives to LC/MS when it is unavailable.