Antibiotic Resistance Profiles and Population Structure of Healthcare-associated and Community-associated Staphylococcus aureus isolated in Fort Portal, Western Uganda

Ackers Johnson, G 2021, Antibiotic Resistance Profiles and Population Structure of Healthcare-associated and Community-associated Staphylococcus aureus isolated in Fort Portal, Western Uganda , PhD thesis, University of Salford.

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Antimicrobials currently hold infectious pathogens at bay, but with cases of resistance ever increasing, those same pathogens have the potential to reverse decades of medical progress, creating one of the biggest threats to global health, food security and development in the world today. The impact of antimicrobial resistance (AMR) is of particular concern for low-income countries which already suffer from a high burden of infectious bacterial diseases in both humans and animals, with cost constraints preventing the widespread application of newer, more expensive agents. Tackling AMR is particularly challenging in settings such as Fort Portal Regional Referral Hospital (FPRRH), Western Uganda, where specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the local area. This study focused on the evaluation of Staphylococcus aureus, a commensal bacterium carried by roughly 30% of the human population commonly in the nasopharynx and/or on skin. S. aureus also acts as a major human pathogen frequently associated with nosocomial infections where the skin has been broken, for example from a wound or surgical procedure. The three core aims of this study involved the evaluation of clinical and community associated S. aureus resistance profiles; evaluation of the population diversity of clinically associated S. aureus; and the elucidation of key resistance associated genes through the whole genome sequencing (WGS) of 41 clinical isolates. A population structure for the 41 sequenced isolates was inferred by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing (MLST) clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. In agreement with other studies, the occurrence of Panton-Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, it was also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. Initial analysis of antimicrobial susceptibility testing (AST) data of S. aureus isolated from both clinical infections at FPRRH and the hand swabs of people in the local community revealed 64% (45/70) and 83% (104/125) of isolates were resistant to one or more antibiotic and 26% (18/70) and 49% (61/125) were multidrug resistant (MDR) respectively. Methicillin-resistant S. aureus (MRSA) was isolated at rates of 38% (8/21) and 22% (27/125) for the clinical and community associated isolates respectively. WGS of the 41 clinical S. aureus isolates revealed resistance phenotypes were largely explained by the presence of antibiotic resistance genes. Although all isolates were susceptible to clindamycin, a 24% carriage of erm genes suggests potential for rapid development of resistance. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower amongst CC152 strains than non-CC152 strains; thus, in keeping with previous work, it was found that CC152 was almost exclusively methicillin-sensitive S. aureus (MSSA). By generating detailed information about the epidemiology of circulating S. aureus and their antibiotic susceptibility, this study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based, including the procurement and prescription of antibiotics. Furthermore, this study was able to build and promote international collaborations between Salford University, FPRRH, Ugandan Infectious Diseases Institute and Makerere University for the effective transfer of knowledge and completion of advanced research.

Item Type: Thesis (PhD)
Schools: Schools > School of Environment and Life Sciences
Depositing User: GAVIN Ackers johnson
Date Deposited: 07 Jun 2022 15:29
Last Modified: 07 Jul 2022 02:30

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