Implications of silver nanoparticles for H. pylori infection: modulation of CagA function and signaling.

Background: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. Methods: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. Results: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. Conclusion: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

Genetic and phenotypic of Pseudomonas aeruginosa sensitive to meropenem antibiotics after exposure to meropenem.

Background and Objectives: Pseudomonas aeruginosa, drug-resistant, causes health infections. Resistance to the preferred therapy meropenem is a serious threat. This study aimed to analyze changes in meropenem minimum inhibitory concentration (MIC), changes in ampC, mexA, and oprD gene expression, and the correlation between MIC and ampC, mexA, and oprD gene expression after meropenem exposure. Materials and Methods: Ten isolates of P. aeruginosa from the Clinical Microbiology Department, Faculty of Medicine, Universitas Indonesia were used. After the bacteria were shown to be sensitive to meropenem phenotypically, intrinsic resistance genes were detected using PCR. After meropenem exposure on Days 5 and 12, sensitivity testing was carried out with the concentration gradient method and RNA was detected using real-time RT-PCR. Results: All P. aeruginosa isolates that were phenotypically sensitive to meropenem had the ampC, mexA, and oprD genes. An increase in MIC, an increase in ampC and mexA gene expression, and a decrease in oprD gene expression were observed after meropenem exposure. There was a very strong and significant correlation (p ≤ 0.05) between MIC and oprD gene expression after Day 12 of meropenem exposure. Conclusion: Although there were no significant differences in MIC and ampC, mexA, and oprD gene expression between Day 5 and Day 12, there was a very strong and significant correlation between MIC and oprD gene expression on Day 12 (p ≤ 0.05). This indicates that decreasing oprD gene expression has the potential to increase meropenem resistance in Pseudomonas aeruginosa.

Antimicrobial Susceptibility of Various MRSA Clinical Isolates and the Impact of Glycopeptide MICs on Clinical and Microbiological Outcomes.

Objective: While vancomycin has remained the mainstay of the treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, there is growing evidence of the clinical impact of increased glycopeptide minimum inhibitory concentrations (MICs) in MRSA isolates. This study aimed to determine the susceptibility of various MRSA isolates to different antibiotics with antistaphylococcal activity and the impact of glycopeptide MICs on clinical and microbiological outcomes. Materials and Methods: This retrospective cohort study, conducted between 2013 and 2017, evaluated the susceptibility of MRSA strains isolated from various clinical samples to antistaphylococcal antibiotics using the gradient strip method. The clinical and laboratory features of patients infected with MRSA isolates with elevated glycopeptide MICs (>1 mg/L) and with isolates that had low glycopeptide MICs (≤1 mg/L) were compared. Results: A total of 104 patients infected with MRSA strains were included in this study. Male sex (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.01-6.10, p=0.048), two or more comorbidities (OR=2.48, 95% CI=1.03-6.50, p=0.044), history of MRSA infection (OR=4.91, 95% CI=1.70-14.28, p=0.003) and a longer hospital stay prior to MRSA infection (OR=2.32, 95% CI=1.05-7.85, p=0.040) were independent risk factors for high glycopeptide MICs. In MRSA infections with a teicoplanin MIC of >0.75mg/L, the microbiological and treatment failures were 46.2% (p=0.044) and 60.6% (p=0.042), respectively. Conclusion: This study showed that the critical MIC value, which suggested treatment failure as well as microbiological failure in the teicoplanin-treated MRSA infections, was >0.75 mg/L rather than >1 mg/L in our study cohort. The identification of high-risk patients;for treatment failures and mortality considering gradient strip method MIC values is crucial for the effective management of MRSA infections.

High-Throughput Monitoring of Pathogenic Fungal Growth Using Whole Slide Imaging for Rapid Antifungal Susceptibility Assessment.

Invasive fungal infections are a major health threat with high morbidity and mortality, highlighting the urgent need for rapid diagnostic tools to detect antifungal resistance. Traditional culture-based antifungal susceptibility testing (AFST) methods often fall short due to their lengthy process. In our previous research, we developed a whole-slide imaging (WSI) technique for the high-throughput assessment of bacterial antibiotic resistance. Building on this foundation, this study expands the application of WSI by adapting it for rapid AFST through high-throughput monitoring of the growth of hundreds of individual fungi. Due to the distinct "budding" growth patterns of fungi, we developed a unique approach that utilizes specific cell number change to determine fungi replication, instead of cell area change used for bacteria in our previous study, to accurately determine the growth rates of individual fungal cells. This method not only accelerates the determination of antifungal resistance by directly observing individual fungal cell growth, but also yields accurate results. Employing Candida albicans as a representative model organism, reliable minimum inhibitory concentration (MIC) of fluconazole inhibiting 100% cells of Candida albicans (denoted as MIC100) was obtained within 3h using the developed method, while the modified broth dilution method required 72h for the similar reliable result. In addition, our approach was effectively utilized to test blood culture samples directly, eliminating the need to separate the fungi from whole blood samples spiked with Candida albicans. These features indicate the developed method holds great potential serving as a general tool in rapid antifungal susceptibility testing and MIC determination.

In Vitro Antibacterial Activities of Fosfomycin against Escherichia coli Isolates from Canine Urinary Tract Infection.

Fosfomycin is a bactericidal drug recommended as an alternative treatment for canine bacterial cystitis, particularly in cases involving multidrug-resistant (MDR) infections when no other options are available. In this study, minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of fosfomycin were determined against 79 clinical E. coli isolates using the agar dilution method. The susceptibility rate of E. coli to fosfomycin was 86.06%, with MIC50 and MIC90 values of 4 mg/L and 96 mg/L, respectively. MPC50 and MPC90 values were 64 mg/L and 192 mg/L. Using pharmacokinetic (PK) data from dogs given a single 80 mg/kg oral dose of fosfomycin, the area under the curve per MIC50 (AUC0-24/MIC50) was 85.79 with time above MIC50 (T > MIC50) exceeding 50%. In urine, the AUC0-24/MIC50 was 10,694.78, and the AUC0-24/MPC90 was 222.81, with T > MPC90 extending beyond 24 h. Therefore, fosfomycin exhibited significant antibacterial activity against canine uropathogenic E. coli, including MDR strains, at concentrations below the susceptible MIC breakpoint. However, the high MPC values, especially the MPC90, indicate the critical importance of performing susceptibility testing for fosfomycin and maintaining ongoing resistance monitoring.

Antimicrobial Activity of Positively Charged Oligopeptides with Theoretical High α-Helix Content against Cutibacterium acnes.

Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13-a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content-against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

The sub-MIC selective window decreases along the digestive tract: determination of the minimal selective concentration of oxytetracycline in sterilised intestinal contents.

Introduction: The administration of antibiotics can expose the digestive microbiota of humans and animals to sub-inhibitory concentrations, potentially favouring the selection of resistant bacteria. The minimal selective concentration (MSC) is a key indicator to understand this process. The MSC is defined as the lowest concentration of an antibiotic that promotes the growth of a resistant strain over a susceptible isogenic strain. It represents the lower limit of the sub-minimal inhibitory concentration (MIC) selective window, where resistant mutants can be selected. Previous studies focused on determining the MSC under standard culture conditions, whereas our research aimed to determine the MSC in a model that approximates in vivo conditions. Methods: We investigated the MSC of oxytetracycline (OTC) in Mueller-Hinton broth (MHB) and sterilised intestinal contents (SIC) from the jejunum, caecum and rectum (faeces) of pigs, using two isogenic strains of Escherichia coli (one susceptible and one resistant to OTC). Additionally, the MIC of OTC against the susceptible strain was determined to assess the upper limit of the sub-MIC selective window. Results: Our study took a novel approach, and the results indicated that MIC and MSC values were lower in MHB than in SIC. In the latter, these values varied depending on the intestinal segment, with distal compartments exhibiting higher MIC and MSC values. Moreover, the sub-MIC selective window of OTC in SIC narrowed from the jejunum to the rectum, with a significantly closer MSC to MIC in faecal SIC. Discussion: The results suggest that OTC binds to digestive contents, reducing the fraction of free OTC. However, binding alone does not fully explain our results, and interactions between bacteria and intestinal contents may play a role. Furthermore, our findings provide initial estimates of low concentrations facilitating resistance selection in the gut. Finally, this research enhances the understanding of antimicrobial resistance selection, emphasising the intricate interplay between antibiotics and intestinal content composition in assessing the risk of resistance development in the gut.

In vitro antibacterial activity of Bersama abyssinica Fresen crude extract against representative Gram-positive and Gram-negative bacterial isolates.

BACKGROUND: Bersama abyssinica Fresen is a plant that is used in folk medicine for the treatment of mastitis and other infectious diseases. OBIECTIVE: The antibacterial activity of methanol crude extract of plant was evaluated against three common bacterial pathogens, including Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli and Pseudomonas aeruginosa). METHODS: The antibacterial activities and minimum inhibitory concentration of B. abyssinica crude extracts were evaluated using agar-well diffusion and broth dilution methods according to the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: A significant difference in the antibacterial activity of crude extracts was observed among different levels of concentration against tested isolates. A higher mean inhibition zone diameter was recorded in E. coli (29.2 ± 1.5 mm), followed by S. aureus (27.8 ± 1.1 mm) and P. aeruginosa (18.0 ± 0.7 mm) at a concentration of 100 mg/mL. The antibacterial activity of crude plant extract at 100 mg/mL was comparable with that of a standard antibiotic (27.6 ± 2.6) against S. aureus and E. coli isolates. The findings indicated that bacterial growth inhibition increased as the concentration of the crude extracts increased. E. coli and S. aureus isolates showed significantly higher susceptibilities to crude extracts than P. aeruginosa at all concentrations. The minimum inhibitory concentrations of extracts against S. aureus, E. coli and P. aeruginosa isolates were 0.78 mg/mL, 1.56 mg/mL and 1.56 mg/mL, respectively. CONCLUSIONS: All tested pathogenic bacterial species were susceptible to plant leaf extract and broad-spectrum activity against Gram-positive and Gram-negative bacteria. The study recommends further fractionation of the B. abyssinica plant that contributes to its antibacterial activity and understands the mode of action of this plant against bacteria and other microbes.

Potential of microbial-derived biosurfactants for oral applications-a systematic review.

BACKGROUND: Biosurfactants are amphiphilic compounds produced by various microorganisms. Current research evaluates diverse types of biosurfactants against a range of oral pathogens. OBJECTIVES: This systematic review aims to explore the potential of microbial-derived biosurfactants for oral applications. METHODOLOGY: A systematic literature search was performed utilizing PubMed-MEDLINE, Scopus, and Web of Science databases with designated keywords. The results were registered in the PROSPERO database and conducted following the PRISMA checklist. Criteria for eligibility, guided by the PICOS framework, were established for both inclusion and exclusion criteria. The QUIN tool was used to assess the bias risk for in vitro dentistry studies. RESULTS: Among the initial 357 findings, ten studies were selected for further analysis. The outcomes of this systematic review reveal that both crude and purified forms of biosurfactants exhibit antimicrobial and antibiofilm properties against various oral pathogens. Noteworthy applications of biosurfactants in oral products include mouthwash, toothpaste, and implant coating. CONCLUSION: Biosurfactants have garnered considerable interest and demonstrated their potential for application in oral health. This is attributed to their surface-active properties, antiadhesive activity, biodegradability, and antimicrobial effectiveness against a variety of oral microorganisms, including bacteria and fungi.

In vitro and in vivo antibacterial activity of selected essential oil components against Pectobacterium carotovorum subsp. carotovorum and Pectobacterium atrosepticum causing bacterial soft rot of potato tubers.

Pectinolytic bacteria cause bacterial soft rot of potato tubers. The most significant losses occur during storage. The efficacy of essential oil (EO) components carvacrol, cinnamaldehyde, d-carvone, l-menthone, R-(+)-limonene and thymol was tested against Pectobacterium carotovorum subsp. carotovorum (Pcc) and Pectobacterium atrosepticum (Pa). Disc diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) tests were performed in vitro, as well as potato disc and whole tuber maceration tests in vivo. Under in vitro conditions, cinnamaldehyde was the most effective against both bacteria (MIC 0.5 µL/mL, MBC 1.5 µL/mL). Both bacteria were found to be more susceptible to d-carvone (MIC 1.5-2.5 µL/mL, MBC 2.5 µL/mL) and thymol (MIC 2.5-5 µL/mL, MBC 3-5 µL/mL). R-(+)-limonene was the least effective. Results from the potato tuber disc maceration test confirmed a significant antibacterial effect of cinnamaldehyde at a concentration of 1.5 µL/mL. No rotted area was observed on potato tuber discs after treatment with l-menthone at concentrations of 2.5 µL/mL and 10 µL/mL against Pcc. A more pronounced effect was obtained when carvacrol was used at concentrations of 5 µL/mL against Pcc and 10 µL/mL against Pa. Disease severity tests on potato tubers after soaking for 20 min at MIC concentration of the EO components followed by 7 days of incubation at room temperature and 15 °C confirmed the antibacterial activity of cinnamaldehyde (0.5 µl/ml), l-menthone (2.5 µl/ml) and carvacrol (5-10 µl/ml). Cinnamaldehyde, l-menthone, and carvacrol may be recommended for further testing to treat stored potato tubers.

The In Vitro Antibacterial Activity of Phytogenic and Acid-Based Eubiotics against Major Foodborne Zoonotic Poultry Pathogens.

The aim of the study was to investigate in vitro the antibacterial activity of 8 commercial drinking water additives against major zoonotic poultry pathogens (Campylobacter spp., Escherichia coli, Salmonella Typhimurium, Staphylococcus aureus and Listeria spp.). We tested two essential oil-based phytogenics (Phyto CSC Liquide B, AEN 350 B Liquid), two acid-based eubiotics (Salgard® liquid, Intesti-Flora), and four blends of essential oils and organic acids (ProPhorceTM SA Exclusive, Herbal acid, Rigosol-N and Eubisan 3000). The antibacterial activity was determined by estimating the minimum inhibitory concentration (MIC) using a microdilution method. The MICs of the products against Campylobacter spp. ranged from 0.071% to 0.568% v/v, in which Herbal acid, a blend rich in lactic and phosphoric acids, also containing thyme and oregano oils, exhibited the highest efficacy (MIC: 0.071% v/v) against all the tested strains. The MICs of the tested products against Escherichia coli ranged between 0.071% and 1.894% v/v. Specifically, the MIC of Rigosol-N, a blend of high concentrations of lactic and acetic acid, was 0.142% v/v for both tested strains, whereas the MICs of Intesti-Flora, a mixture rich in lactic and propionic acid, ranged from 0.284% to 0.568% v/v. The MICs of the products against Salmonella Typhimurium were between 0.095% and 1.894% v/v. Specifically, the MIC of Eubisan 3000, a blend rich in oregano oil, was 0.284% v/v. The MICs against Staphylococcus aureus were between 0.142% and 9.090% v/v. The MICs of Phyto CSC Liquide B, which is rich in trans-cinnamaldehyde, were between 3.030% and 9.090% v/v, showing the highest MIC values of all tested products. Finally, the MIC values of the tested commercial products against Listeria spp. were 0.095% to 3.030% v/v. The MICs of ProPhorceTM SA Exclusive, a highly concentrated blend of formic acid and its salts, were 0.095-0.142% v/v against Listeria spp., while the MICs of AEN 350 B Liquid were between 0.284% and 1.894% exhibiting high Listeria spp. strain variability. In conclusion, all the selected commercial products exhibited more or less antibacterial activity against pathogenic bacteria and, thus, can be promising alternatives to antibiotics for the control of zoonotic poultry pathogens and the restriction of antimicrobial-resistant bacteria.

Antifungal Activity of Aniba canelilla (Kunth) Mez Essential Oil and Its Main Compound 1-Nitro-2-Phenylethane against Dermatophytes.

The essential oil of Aniba canelilla (Kunth) Mez (EOAC), an Amazon plant composed of a rare nitro compound, has shown scientific evidence of antifungal activity but is still unexplored against dermatophytes. The antifungal susceptibility of EOAC and its main compound, 1-nitro-2-phenylethane (NP), was evaluated against dermatophytes (Trichophyton rubrum, T. mentagrophytes and Microsporum canis), evidencing antifungal activity with an inhibitory concentration lower than 256 µg/mL. The mechanism of action was also evaluated, and it is suggested that EOAC and NP have fungicidal action in the fungal membrane, since the antifungal activity occurs through a modification of the shape of the conidial structures of the fungus, showing the permeability of the intracellular content due to the visually observed plasmolysis and cytosolic extravasation through an osmotic process. These results suggest the essential oil and its main compound are promising plant-derived alternatives for treating ungual dermatophytosis.

Mechanistic Study of Antimicrobial Effectiveness of Cyclic Amphipathic Peptide [R4W4] against Methicillin-Resistant Staphylococcus aureus Clinical Isolates.

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP.

Machine Learning Tools to Assist the Synthesis of Antibacterial Carbon Dots.

Introduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species. Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools. Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, ε-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction. Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation.

Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

Investigating inhibiting factors affecting seed germination index in kitchen waste compost products: Soluble carbon, nitrogen, and salt insights.

The seed germination index (GI) serves as the principal determinant that impedes the integration of aerobic composting products into agricultural lands. The current research work predominantly focuses on exploring the correlation between physical and chemical indicators of the compost products and GI, neglecting the fundamental cause. This study systematically analyzed the composition of GI aqueous extracts from compost products derived from kitchen waste under various composting methodologies, with nitrogen, carbon, and inorganic salt as critical factors. The analytical work concluded that acetic acid, formic acid, and ammonium were the inhibitory factors influencing GI. Validation experiments introduced inhibitory factors, yielding a functional relationship formula depicting GI variations due to a single influential factor. This study conclusively identified acetic acid as the primary constraint, establishing that its inhibitory concentration corresponded to 70 % GI stands at 85 mg/L. This study will provide guidelines for the future research on enhancing aerobic composting techniques.

Antifungal Activity of Neem Leaf Extract With Eucalyptus citriodora Oil and Cymbopogon martini Oil Against Tinea Capitis: An In-Vitro Evaluation.

Introduction Tinea capitis, often known as ringworm of the scalp, is a fungal infection that affects the scalp, eyelashes, and eyebrows. It is generally caused by dermatophytes from the genera Trichophyton and Microsporum. Trichophyton tonsurans and Microsporum canis are the main etiological agents responsible for most of the cases of tinea capitis globally. Tinea capitis commonly manifests as itchy, scaly patches of hair loss. Tinea capitis is the prevailing dermatophyte illness among children globally. Methods An in-vitroevaluation study was conducted to assess the antifungal properties of ethanolic extracts of neem leaves and the oils of Eucalyptus citriodora and Cymbopogon martini, both individually and in combination. The agar-well diffusion method and the M38-A2 microbroth dilution method were employed to evaluate the antifungal efficacy against pathogenic dermatophyte strains, namely Microsporum canis and Trichophyton tonsurans. The fully mature green leaves were treated with ethanol to make the neem leaf extract. Additionally, high-performance liquid chromatographic analysis was carried out to determine the contents of the terpenoids. Fluconazole, an antifungal drug, is used as a standard. Results The findings demonstrated an overall inhibition of the growth of dermatophytes at a minimal inhibitory concentration of 187.5 and 375 µg/ml for neem leaf extract and 0.625 to 2.5 µl/ml for selected herbal oils, whereas it was 0.25 µg/ml and 0.50 µg/ml for positive control against Microsporum canis and Trichophyton tonsurans, respectively. Conclusion The phytochemical investigation of the ethanolic extracts in neem leaves revealed the presence of terpenoids, which are known for their significant biological activity. The study's findings demonstrated the therapeutic capabilities of neem leaf extract in combination with the oils of Eucalyptus citriodora and Cymbopogon martini for managing the tinea capitis infection. A broader and improved antifungal spectrum was seen when neem leaf extract and oils were combined. Therefore, it can be developed into a suitable formulation for the management of tinea capitis.

An In Vitro Study to Evaluate the Antimicrobial Activity of a Zinc Citrate, Sodium Fluoride, Alum and Xylitol-Based Toothpaste Formulation.

INTRODUCTION: Periodontitis is a prevalent condition significantly affecting oral health. Comorbid conditions, such as diabetes, can heighten the severity of periodontal disease and overall oral health. Therefore, to enhance oral health and manage comorbid conditions, comprehensive periodontal care is essential. This approach could involve using toothpaste containing antimicrobial ingredients in routine oral care. This paper presents the results of an in vitro study analysing the antimicrobial properties of the test formulation containing zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste (Stolin-R). These ingredients work together to help in providing comprehensive oral care by controlling growth of bacteria majorly responsible for periodontal disease and thus maintaining optimal oral hygiene. AIM: To determine the antimicrobial properties of zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation against key periodontal pathogens through in vitro analyses. MATERIALS AND METHODS: The antimicrobial efficacy of test formulation is evaluated through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-dependent antibacterial assessment against key periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus mutans, and Bacteroides fragilis. RESULTS: The test formulation demonstrated potent antimicrobial effectiveness against Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, and Tannerella forsythia, by exhibiting low MIC and MBC. Additionally, significant bacterial reduction, exceeding 99.99%, was observed within five minutes, emphasising its potential as an effective adjunct in combating periodontal infection. CONCLUSION: Zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation demonstrates significant antimicrobial activity against key periodontal pathogens, suggesting its potential as an effective agent for maintaining oral health and combating gingival infection.

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia.

Purpose: Azole resistance in Aspergillus fumigatus poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and cyp51A mutation profiles of A. fumigatus isolates in Malaysia. Patients and Methods: Sixty clinical A. fumigatus isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC50/MIC90 for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against A. fumigatus in non-invasive cases and invasive cases were calculated. In addition, the presence of cyp51A mutations was also identified. Results: The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various cyp51A mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance. Conclusion: The majority of clinical Aspergillus fumigatus isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, cyp51A mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.