Saudi Cultural Missions Theses & Dissertations
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Item Restricted The effect of corticosteroids on sinus microbiota in chronic rhinosinusitis patients with nasal polyposis(McGill University, 2019) Alammar, Yousif; Rousseau, Simon; Tewfik, Marc; Rousseau, Simon; Tewfik, MarcBackground: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease with no known single cause, but it is thought that bacteria play a role in the disease process. The short-term response of bacterial communities to corticosteroid therapy has been found to be unpredictable. As a result, this pilot study aims to assess the long-term effect of corticosteroid therapy on sinus microbiota in chronic rhinosinusitis patients with nasal polyposis (CRSwNP). Methods: A longitudinal prospective case-control study was done on patients with CRSwNP and on healthy subjects. Patients with CRSwNP were randomly allocated to a maximal medical therapy (corticosteroids and antibiotics) treatment group or a corticosteroid-only treatment group. Data was collected at 3 time points (before treatment, 1 and 3 months after treatment): A guarded sinus swab was collected from the middle meatus; the SNOT-22 questionnaire was used to assess clinical symptoms. Specimens were cultured and Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) was used as a bacterial detection method. The raw data produced was analyzed to characterize the sample and to assess the response to each medical treatment. Results: Data from 29 patients with CRSwNP (16 maximal medical therapy; 13 corticosteroids only) was compared to 15 healthy subjects. Patients reported significant symptoms improvement initially (1- month), but not on the long-term (3-months). This result was found as a response to both treatment groups, whether or not antibiotics was used. There was no significant difference in the sinus microbiota prevalence between CRSwNP patients and normal subjects. After three months from treatment, Corynebacterium genera tended to increase in the maximal medical therapy group, while Staphylococcus and gram-negative genera (Pseudomonas) tended to increase after corticosteroid treatment. Smoking, aspirin sensitivity and previous endoscopic sinus surgery were found to be co-factors significantly associated with the response to systemic corticosteroid therapy. Conclusion: In this pilot study both treatment options were effective on the short-term, but not on the long-term with no clear sinus microbiota response linked. As a result, this study agrees with previous reports that discourage the use of systemic antibiotics without evidence of active infection.14 0Item Restricted Approaches to rejuvenate antibiotic discovery: new sources, new tools(University of leeds, 2023-02-24) Almufarriji, Fawaz; O'Neill, Professor AlexOwing to the widespread use, overuse, and abuse of antibiotics, pathogenic bacteria have evolved extensive antibiotic resistance in recent decades. Over that same period, there has been a dramatic decline in the discovery of novel antibiotics. The failure of target-based screening using synthetic chemical libraries to discover novel classes of antibacterial drugs has renewed interest in returning to the best validated source of antibiotics i.e., natural products. However, it is self-evident that screening the same producer organisms with the same approaches used in the past will result in the rediscovery of already-known antibiotics. Therefore, new sources of natural products should be screened to access novel scaffolds and innovative discovery tools should be developed to more effectively screen established and novel sources. The work in this thesis has contributed to both of these aims. In the first instance, this study has validated clinically-isolated fungi as a novel source of antibiotics. Of 3,560 isolates screened, 12 were shown to produce apparently novel antibiotics with selective antibacterial activity that encompasses the ESKAPE pathogens. This work also describes the generation and validation of pathway-specific whole-cell biosensors for the detection of protein biosynthesis inhibitors (PBIs) that show unprecedented specificity and sensitivity. One these biosensors was engineered to contain multiple common PBI resistance genes, thereby achieving in-built dereplication for the deselection of known PBIs. Screening of >7,400 microbial extracts from the national cancer institute (NCI) natural products library for novel PBIs identified 99 putative hits; re-screening using the dereplicator strain recovered only two hits, underscoring both the utility of the whole-cell biosensor for identification of PBIs in a screening context, and the power of the dereplication function for removing known compounds from further consideration.25 0Item Restricted Audit of Reserve Antibiotic Prescribing in a Tertiary Care Centre in London(2023-03-31) Alshalan, Noura; Thangarajah, RajeniBackground: Antimicrobial Stewardship (AMS) promotes the monitoring of appropriate use of antibiotics in order to preserve their long-term efficacy. The project aims to review the current practice of reserve (restricted) antibiotics prescribing within the trust based on AMS principles. Methods: A retrospective evaluation of (AMS) daily reports and clinical notes were inspected to collect data such as: name of reserve antibiotic, indication, duration, allergy status, date and time of prescription, missed doses and infectious diseases specialist approval. Results: The findings show that there were 295 Reserve antibiotic prescriptions written between October 2022 and February 2023, and five reserve antibiotics in total were prescribed. 93% of these prescriptions had documentation of the indication, and 82% had documentation of an infectious disease (ID) specialist approval. 73% of these prescriptions included documentation of the duration of reserve antibiotic regimens. Conclusion: Antimicrobial Stewardship (AMS) principles indicate that documenting treatment plans is considered good practice, and in order to effectively manage antibiotic use, promote better documentation and improve prescribing practice, it is critical to educate not only prescribers but also all other healthcare providers that interact with patients who have received an antibiotic.6 0Item Restricted Knowledge of Molar Incisor Hypomineralization among Physicians and Dentists(Saudi Digital Library, 2023) Ghazal, Ebtehal; Kulkarni, GajananObjectives: To assess the knowledge of physicians and dentists on Molar Incisor Hypomineralization (MIH) and its association with antibiotic exposure during early childhood. Methods: A cross-sectional survey design was utilized. The study was electronically advertised through professional organizations with a hyperlink provided to the questionnaire. Chi-square test was used to compare differences in levels of knowledge between the study groups. Results: There were 335 participants in the study; general physicians (n=79), pediatricians (n=98) and dentists (n=158). A significantly lower proportion of general physicians (19%) and pediatricians (18%) had knowledge of molar incisor hypomineralization compared to dentists (82%, P<0.001). There was no statistically significant difference between the groups regarding the association between antibiotics prescribed during the first years of life and MIH development (P=0.07). Conclusions: Physicians lacked knowledge about the MIH dental condition. Most study respondents did not know the potential association between MIH and frequent antibiotic intake during early childhood.47 0