The fungicidal effectiveness of 2-Chloro-3-hydrazinylquinoxaline, a newly developed quinoxaline derivative, against Candida species.

BACKGROUND: Candida represents a prevalent fungal infection, notable for its substantial implications on morbidity and mortality rates. In the landscape of prospective treatments, quinoxaline derivatives emerge as a category of compact compounds exhibiting notable potential in addressing infections. These derivatives showcase promising antimicrobial efficacy coupled with favorable pharmacokinetic and safety characteristics. AIMS: The central aim of this investigation was to examine the antifungal characteristics of 2-Chloro-3-hydrazinylquinoxaline against diverse strains of Candida and Aspergillus in vitro. Additionally, we endeavored to assess the in vivo efficacy of 2-Chloro-3-hydrazinylquinoxaline using a murine model for oral candidiasis induced by C. albicans cells ATCC 10231. RESULTS: 2-Chloro-3-hydrazinylquinoxaline demonstrated noteworthy effectiveness when tested against various reference strains of Candida species. It exhibited heightened efficacy, particularly against Candida krusei isolates. However, its performance against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida auris isolates exhibited variability. Notably, 2-Chloro-3-hydrazinylquinoxaline manifests variable efficacy against Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus and Aspergillus flavus and no effect against Aspergillus brasiliensis. In a murine model, 2-Chloro-3-hydrazinylquinoxaline exhibited significant efficacy in combating the C. albicans cells ATCC 10231 strain, underscoring its potential as a viable treatment option. CONCLUSION: 2-Chloro-3-hydrazinylquinoxaline has demonstrated substantial potential in effectively addressing various Candida and Aspergillus species, showcasing dual attributes of antifungal and anti-inflammatory properties. However, to attain a more comprehensive understanding of its therapeutic capabilities, further investigations, incorporating additional tests and experiments, are imperative.

The Prevalence and Risk Factors of Trichosporonosis at King Abdulaziz University Hospital.

Background: Fungal infections, especially those caused have emerged as a significant medical concern over the past three decades, particularly among immunocompromised patients. However, recent studies have highlighted the increasing prevalence of fungal infections resembling yeast other than Candida, such as trichosporonosis, especially among immunosuppressed individuals worldwide. Trichosporon has been identified as a significant contributor to superficial and invasive infections. Invasive trichosporonosis, primarily affecting immunocompromised patients, poses a significant threat with high mortality rates. Purpose: The current study aimed to explore the clinical epidemiology of Trichosporon spp at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. Methods: This retrospective study aimed to assess the clinical epidemiology of Trichosporon spp. infections in microbiology cultures obtained from KAUH in Saudi Arabia. The study analyzed data from patients over a five-year period, focusing on demographic, clinical, and microbiological characteristics. Results: This study encompassed 21 participants, categorized into four distinct age groups. Moreover, this study indicated T. asahii as the predominant species isolated, accounting for 90.5% of infections, followed by T. mucoides (9.5%). ICU hospitalization, diabetes mellitus, taking immunosuppressive drugs, and antifungal drugs, and the use of invasive medical equipment were identified as prominent risk factors for trichosporonosis. Urinary tract infections were the most common clinical presentation, particularly among male and elderly patients. Mortality rates were high, especially among older individuals. Conclusion: This study contributes valuable epidemiological insights into trichosporonosis, highlighting the need for enhanced surveillance and preventive strategies in healthcare settings. Further research is warranted to optimize treatment approaches and infection control measures, ultimately reducing the burden of Trichosporon infections on patient outcomes.

Multidrug-Resistant Bacterial Infections in Pediatric Patients Hospitalized at King Abdulaziz University Hospital, Jeddah, Western Saudi Arabia.

Multidrug-resistant bacterial infections (MDRIs) constitute a major global threat due to increased patient morbidity/mortality and hospital stay/healthcare costs. A few studies from KSA, including our locality, addressed antimicrobial resistance in pediatric patients. This study was performed to recognize the incidence and clinical/microbiologic features of MDRIs in hospitalized pediatric patients. A retrospective cross-sectional study included pediatric patients < 18 years, admitted to King Abdulaziz University Hospital, between October 2021 and November 2022, with confirmed positive cultures of bacteria isolated from blood/body fluids. Patients' medical files provided the required data. MDR organisms (MDROs) were identified in 12.8% of the total cultures. The incidence of MDRIs was relatively high, as it was detected in 42% of patients and in 54.3% of positive bacterial cultures especially among critically ill patients admitted to the NICU and PICU. Pneumonia/ventilator-associated pneumonia was the main type of infection in 37.8% of patients with MDROs. Klebsiella pneumoniae was the most common significantly isolated MDRO in 39.5% of MDR cultures. Interestingly, a low weight for (no need for their as terminology weight for age is standard and well-known) was the only significant risk factor associated with MDROs (p = 0.02). Mortality was significantly higher (p = 0.001) in patients with MDROs (32.4%) than in patients without MDROs (3.9%). Patients who died including 85.7% of patients with MDROs had significantly longer durations of admission, more cultures, and utilized a larger number of antibiotics than the surviving patients (p = 0.02, p = 0.01, p = 0.04, respectively). This study provided a comprehensive update on the seriously alarming problem of MDROs, and its impacts on pediatric patients. The detected findings are crucial and are a helpful guide to decid for implementing effective strategies to mitigate MDROs.

Synergistic Activity of 3-Hydrazinoquinoxaline-2-Thiol in Combination with Penicillin Against MRSA.

Background: The growing resistance seen in various antibiotics, including those considered as last-resort options, underscores the pressing need for novel approaches and new substances to address MRSA infections. Combining antibiotics as a treatment approach can enhance effectiveness, expand the range of targeted bacteria, and minimize the likelihood of resistance emergence. This approach holds promise in addressing the escalating issue of antibiotic resistance. Purpose: This study seeks to investigate the potential synergy between 3-hydrazinoquinoxaline-2-thiol and penicillin against a diverse array of MRSA isolates, thereby providing insights into their combined antimicrobial action. Methods: Twenty-two clinical MRSA isolates subjected to broth microdilution to determine the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and penicillin. Subsequently, a checkerboard assay was employed to evaluate the interaction between 3-hydrazinoquinoxaline-2-thiol and penicillin, focusing on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of penicillin and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical MRSA strains. Penicillin exhibited MICs within a range of 1024 to 128 µg/mL, while 3-hydrazinoquinoxaline-2-thiol displayed MICs varying from 64 to 8 µg/mL. Remarkably, the combination of 3-hydrazinoquinoxaline-2-thiol and penicillin yielded a synergistic effect, resulting in a significant reduction of MICs by up to 64-fold. Conclusion: The potential of 3-hydrazinoquinoxaline-2-thiol in combination with penicillin as a viable solution against MRSA appears promising. However, to establish its practical utility, further extensive testing and experiments are essential.

Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis.

Mycobacterium tuberculosis is responsible for tuberculosis (TB) all over the world. Despite tremendous advancements in biomedical research, new treatment approaches, and preventive measures, TB incidence rates continue to ascend. The herbaceous plant Acalypha indica, also known as Indian Nettle, belongs to the Euphorbiaceae family and is known as one of the most important sources of medicines and pharmaceuticals for the medical therapy for a range of ailments. However, the precise molecular mechanism of its therapeutic action is still unknown. In this study, an integrated network pharmacology approach was employed to explore the potential mechanism of A. indica phytochemicals against TB. The active chemical components of A. indica were collected from two independent databases and published sources, whereas SwissTargetPrediction was used to identify the target genes of these phytochemicals. GeneCards and DisGeNET databases were employed to retrieve tuberculosis-related genes and variants. Following the evaluation of overlapped genes, gene enrichment analysis and PPI network analysis were performed using the DAVID and STRING databases, respectively. Later, to identify the potential target(s) for the disease, molecular docking was performed. A. indica revealed 9 active components with 259 potential therapeutic targets; TB attributed 694 intersecting genes from the two data sets; and both TB and A. indica overlapped 44 potential targets. The in-depth analysis based on the degree revealed that AKT1 and EGFR formed the foundation of the PPI network. Moreover, docking analysis followed by molecular dynamics simulations revealed that phytosterol and stigmasterol have higher binding affinities to AKT1 and EGFR to suppress tuberculosis. This study provides a convincing proof that A. indica can be exploited to target TB after experimental endorsement; further, it lays the framework for more experimental research on A. indica's anti-TB activity.

Livelihood activities, human mobility, and risk of malaria infection in elimination settings: a case-control study.

BACKGROUND: Livelihood activities and human movements participate in the epidemiology of vector-borne diseases and influence malaria risk in elimination settings. In Saudi Arabia, where malaria transmission intensity varies geographically, it is vital to understand the components driving transmission within specific areas. In addition, shared social, behavioural, and occupational characteristics within communities may provoke the risk of malaria infection. This study aims to understand the relationship between human mobility, livelihood activities, and the risk of malaria infection in the border region of Jazan to facilitate further strategic malaria interventions. In addition, the study will complement and reinforce the existing efforts to eliminate malaria on the Saudi and Yemen border by providing a deeper understanding of human movement and livelihood activities. METHODS: An unmatched case-control study was conducted. A total of 261 participants were recruited for the study, including 81 cases of confirmed malaria through rapid diagnostic tests (RDTs) and microscopy and 180 controls in the Baish Governorate in Jazan Provinces, Saudi Arabia. Individuals who received malaria tests were interviewed regarding their livelihood activities and recent movement (travel history). A questionnaire was administered, and the data was captured electronically. STATA software version 16 was used to analyse the data. Bivariate and multivariate analyses were conducted to determine if engaging in agricultural activities such as farming and animal husbandry, recent travel history outside of the home village within the last 30 days and participating in spiritual gatherings were related to malaria infection status. RESULTS: A logistical regression model was used to investigate components associated with malaria infection. After adjusting several confounding factors, individuals who reported travelling away from their home village in the last 30 days OR 11.5 (95% CI 4.43-29.9), and those who attended a seasonal night spiritual gathering OR 3.04 (95% CI 1.10-8.42), involved in animal husbandry OR 2.52 (95% CI 1.10-5.82), and identified as male OR 4.57 (95% CI 1.43-14.7), were more likely to test positive for malaria infection. CONCLUSION: Human movement and livelihood activities, especially at nighttime, should be considered malaria risk factors in malaria elimination settings, mainly when the targeted area is limited to a confined borderland area.

Green Synthesis of Zn(OH)2/ZnO-Based Bionanocomposite using Pomegranate Peels and Its Application in the Degradation of Bacterial Biofilm.

The ability and potency of bacterial species to form biofilms, which show antibiotic resistance thereby avoiding antibiotic surfaces, is a major cause of prolonged infections. Various advanced approaches have been employed to prevent or damage bacterial biofilms, formed by a variety of bacterial strains, to help prevent the associated infectious disease. In this context, zinc-based nanostructures have been recognized as a potential antibiotic agent against a broad spectrum of bacterial communities. As a result, a sustainable and green synthesis method was adapted in the present study to synthesize a Zn(OH)2/ZnO-based bionanocomposite, in which aqueous extracts of waste pomegranate peels (Punica granatum) were employed as a natural bioreducing agent to prepare the bionanocomposite at room temperature. Furthermore, FT-IR, XRD, DLS, UV-Visible, PL spectroscopy, FE-SEM, and TEM were used to characterize the green route synthesized a Zn(OH)2/ZnO bionanocomposite. The average crystallite size was determined using the Scherrer relation to be 38 nm, and the DLS results indicated that the Zn(OH)2/ZnO bionanocomposite had a hydrodynamic size of 170 nm. On the other hand, optical properties investigated through UV-Vis and PL spectroscopy explored the energy bandgap between 2.80 and 4.46 eV, corresponding to the three absorption edges, and it covered the blue spectrum when the sample was excited at 370 nm. Furthermore, the impact of this green route synthesized a Zn(OH)2/ZnO bionanocomposite on the biofilm degradation efficiency of the pathogenic bacterial strain Bacillus subtilis PF_1 using the Congored method was investigated. The Congored assay clearly explored the biofilm degradation efficiency in the presence of a 50 mg/mL and 75 mg/mL concentration of the Zn(OH)2/ZnO bionanocomposite against the bacterial strain Bacillus subtilis PF_1 grown for 24 h. This study can be further applied to the preparation of bionanocomposites following a low-cost green synthesis approach, and thus prepared nanostructures can be exploited as advanced antimicrobial agents, which could be of great interest to prevent various infectious diseases.

Determinants of Response at 2 Months of Treatment in a Cohort of Pakistani Patients with Pulmonary Tuberculosis.

Mycobacterium tuberculosis infection continues to be a major global challenge. All patients with pulmonary tuberculosis are treated with a standard 6-month treatment regimen. Historical data suggest that even with shortened treatment, most patients achieve long-term remission. Risk stratification is a goal for reducing potentially toxic prolonged treatment. This study aimed to determine the factors associated with the early clearance of sputum acid-fast bacilli (AFB). A total of 297 freshly diagnosed patients with pulmonary tuberculosis were included and enrolled in this study. Information related to their ethno-demographic and anthropometric characteristics was collected. We also assessed their complete blood counts, and blood iron, folate, and vitamin B12 levels. We found that the presence of higher levels of acid-fast bacilli (AFB) in diagnostic sputum microscopy was the single most significant prognostic factor associated with early clearance of sputum AFB after 2 months of treatment. All of our patients achieved treatment success after 6 months of treatment and were disease free. Our results support the data obtained from previous studies indicating that AFB clearance at 2 months is unlikely to be a clinically useful biomarker or indicator for therapeutic stratification. Furthermore, demographic, anthropometric, and nutritional factors are not clinically useful biomarkers.

Aflatoxins in Cereals and Cereal-Based Products: Occurrence, Toxicity, Impact on Human Health, and Their Detoxification and Management Strategies.

Cereals and cereal-based products are primary sources of nutrition across the world. However, contamination of these foods with aflatoxins (AFs), secondary metabolites produced by several fungal species, has raised serious concerns. AF generation in innate substrates is influenced by several parameters, including the substrate type, fungus species, moisture content, minerals, humidity, temperature, and physical injury to the kernels. Consumption of AF-contaminated cereals and cereal-based products can lead to both acute and chronic health issues related to physical and mental maturity, reproduction, and the nervous system. Therefore, the precise detection methods, detoxification, and management strategies of AFs in cereal and cereal-based products are crucial for food safety as well as consumer health. Hence, this review provides a brief overview of the occurrence, chemical characteristics, biosynthetic processes, health hazards, and detection techniques of AFs, along with a focus on detoxification and management strategies that could be implemented for food safety and security.

Improved biohydrogen production via graphene oxide supported granular system based on algal hydrolyzate, secondary sewage sludge and bacterial consortia.

Biohydrogen production using renewable sources has been regarded as one of the most sustainable ways to develop low-cost and green production technology. In order to achieve this objective, herein biohydrogen production has been conducted using the combination of untreated secondary sewage sludge (Sss), algal biomass hydrolyzate (Abh), graphene oxide (GO) and bacterial consortia that forms a granular system. Thus, naturally formed granular system produced cumulative H2 of 1520 mL/L in 168 h with the maximum production rate of 13.4 mL/L/h in 96 h at initial pH 7.0, and optimum temperature of 37 °C. It is noticed that the combination of Abh, Sss and GO governed medium showed 42.05 % higher cumulative H2 production along with 22.71 % higher production rate as compared to Abh and Sss based H2 production medium. The strategy presented herein may find potential applications for the low-cost biohydrogen production using waste biomasses including Sss and Abh.

Exposure to a Manuka Honey Wound Gel Is Associated With Changes in Bacterial Virulence and Antimicrobial Susceptibility.

The use of manuka honey for the topical treatment of wounds has increased worldwide owing to its broad spectrum of activity towards bacteria in both planktonic and biofilm growth modes. Despite this, the potential consequences of bacterial exposure to manuka honey, as may occur during the treatment of chronic wounds, are not fully understood. Here, we describe changes in antimicrobial susceptibility and virulence in a panel of bacteria, including wound isolates, following repeated exposure (ten passages) to sub-inhibitory concentrations of a manuka honey based wound gel. Changes in antibiotic sensitivity above 4-fold were predominantly related to increased vancomycin sensitivity in the staphylococci. Interestingly, Staphylococcus epidermidis displayed phenotypic resistance to erythromycin following passaging, with susceptibility profiles returning to baseline in the absence of further honey exposure. Changes in susceptibility to the tested wound gel were moderate (≤ 1-fold) when compared to the respective parent strain. In sessile communities, increased biofilm eradication concentrations over 4-fold occurred in a wound isolate of Pseudomonas aeruginosa (WIBG 2.2) as evidenced by a 7-fold reduction in gentamicin sensitivity following passaging. With regards to pathogenesis, 4/8 bacteria exhibited enhanced virulence following honey wound gel exposure. In the pseudomonads and S. epidermidis, this occurred in conjunction with increased haemolysis and biofilm formation, whilst P. aeruginosa also exhibited increased pyocyanin production. Where virulence attenuation was noted in a passaged wound isolate of S. aureus (WIBG 1.6), this was concomitant to delayed coagulation and reduced haemolytic potential. Overall, passaging in the presence of a manuka honey wound gel led to changes in antimicrobial sensitivity and virulence that varied between test bacteria.