• Goodhead, Ian
• Walwema, Richard
• Ackers-Johnson, Gavin
• Nsubuga, Moses L.
• Kajumbula, Henry
• Kibombo, Daniel
• Kusiima, Brenda
• Kigozi, Edgar
• James, Chloë E.
• Kateete, David Patrick
• Birtles, Richard
• Ackers, Helen Louise

Abstract

<jats:p>Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 <jats:italic><jats:named-content content-type="species"><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.11043" xlink:type="simple">Staphylococcus aureus</jats:ext-link></jats:named-content></jats:italic> isolates (2017–2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant <jats:italic><jats:named-content content-type="species"><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.11043" xlink:type="simple">S. aureus</jats:ext-link></jats:named-content></jats:italic> (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of <jats:italic>erm</jats:italic> genes suggests potential for rapid development of resistance. We inferred a population structure for the <jats:italic><jats:named-content content-type="species"><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.11043" xlink:type="simple">S. aureus</jats:ext-link></jats:named-content></jats:italic> isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive <jats:italic><jats:named-content content-type="species"><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.11043" xlink:type="simple">S. aureus</jats:ext-link></jats:named-content></jats:italic> (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton–Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating <jats:italic><jats:named-content content-type="species"><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.11043" xlink:type="simple">S. aureus</jats:ext-link></jats:named-content></jats:italic> and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.</jats:p>

Topics

• impedance spectroscopy
• cluster
• susceptibility