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

Ghassan J Alboloshi,1 Asif A Jiman-Fatani,2,3 Dalya Attallah,3 Jawahir A Mokhtar,2– 4 Nabeela Abdullah Al-Abdullah,5,6 Khalil Alkuwaity,4,7 Reham Kaki,6,8 Mohammed W Al-Rabia,2 Abdelbagi Alfadil,2,9 Karem Ibrahem,2 Addisu D Teklemariam,10,11 Steve Harakeh12,13 1Department of Medical Laboratories, King Abdullah Medical Complex Jeddah, Ministry of Health, Jeddah, Saudi Arabia; 2Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Clinical and Molecular Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; 4Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Public Health, College of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Infection Control and Environmental Health, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; 7Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 8Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 9Center of Research Excellence for Drug Research and Pharmaceutical Industries, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 10Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 11Department of MIVP, College of Veterinary Medicine and Agriculture, Addis Ababa University, Addis Ababa, Ethiopia; 12King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 13Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Abdelbagi Alfadil, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, King Abdulaziz University, 21589, Saudi Arabia, Tel +96612 6952000 Ext 21062, Email [email protected]: 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.Keywords: fungal infection, trichosporonosis, Trichosporon spp, Trichosporon asahii, invasive, risk factor

The Combination of 3-Hydrazinoquinoxaline-2-Thiol with Thymoquinone Demonstrates Synergistic Activity Against Different Candida Strains

Mohammed A Bazuhair,1,2 Mohammed Alsieni,1 Hani Abdullah,3 Jawahir A Mokhtar,3– 5 Dalya Attallah,4 Turki S Abujamel,5,6 Khalil K Alkuwaity,5,6 Hanouf A Niyazi,3 Hatoon A Niyazi,3 Hind AbdulMajed,3 Noha Juma,3 Mohammed W Al-Rabia,3 Abdelbagi Alfadil,2,3 Karem Ibrahem3 1Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia; 5Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Karem Ibrahem, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +966 562525685, Email [email protected]: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds.Methods: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI).Results: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 μg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 μg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains.Conclusion: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.Keywords: Candida spp, antimicrobial resistance, 3-hydrazinoquinoxaline-2-thiol, thymoquinone, MIC, FIC

Regulatory role of CD8(+ )T lymphocytes in bone marrow eosinophilopoiesis

BACKGROUND: There is a growing body of evidence to suggest that CD8(+ )T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8(+ )T lymphocytes, as well as CD4(+ )T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3(+ )T lymphocytes (NJ.1638; CD3(IL-5+ )mice) were bred with gene knockout mice lacking either CD4(+ )T lymphocytes (CD4(-/-)) or CD8(+ )T lymphocytes (CD8(-/-)) to produce CD3(IL-5+ )knockout mice deficient in CD4(+ )T lymphocytes (CD3(IL-5+)/CD4(-/-)) and CD8(+ )T lymphocytes (CD3(IL-5+)/CD8(-/-)), respectively. Secondly, CD3(+), CD4(+ )and CD8(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3(IL-5+), CD3(IL-5+)/CD8(-/- )and CD3(IL-5+)/CD4(-/- )mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3(IL-5+)/CD8(-/- )mice compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. Serum IL-5 was significantly higher in CD3(IL-5+)/CD4(-/- )mice compared to CD3(IL-5+ )mice but there was no difference in serum IL-5 between CD3(IL-5+)/CD4(-/- )and CD3(IL-5+)/CD8(-/- )mice. Adoptive transfer of CD8(+), but not CD4(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3(IL-5+)/CD8(-/- )mice developed lower numbers of BM eosinophils compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. CONCLUSION: This study shows that CD8(+ )T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice

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

Abdelbagi Elfadil, Karem Ibrahem, Hani Abdullah, Jawahir A Mokhtar, Mohammed W Al-Rabia, Hafsa Alawad Mohammed Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabicCorrespondence: Abdelbagi Elfadil, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +96612 6952000 Ext:21062, Email [email protected]: 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.Keywords: penicillin, antibiotic combination therapy, drug discovery, 3-hydrazinoquinoxaline-2-thio