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Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa
Thesis (PhD)--Stellenbosch University, 2025.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867614126443855872 |
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| access_status_str | Open Access |
| author | Moloto, Kedisaletse |
| author2 | Newton-Foot, Mae |
| author_browse | Moloto, Kedisaletse Newton-Foot, Mae |
| author_facet | Newton-Foot, Mae Moloto, Kedisaletse |
| author_sort | Moloto, Kedisaletse |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/134313 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:47:05.324Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/134313 Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa Moloto, Kedisaletse Newton-Foot, Mae Whitelaw, Andrew Dramowski, Angela Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Division of Medical Microbiology. Thesis (PhD)--Stellenbosch University, 2025. Moloto, K. 2025. Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa. Unpublished doctoral thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/f2f6af25-bfc7-4ab2-9a5c-13944695ca3a Carbapenem resistant Enterobacterales (CRE) are listed by the World Health Organization as as a serious threat to public health. In early 2019, an outbreak of CRE in the neonatal unit at Tygerberg Hospital, a tertiary hospital in Cape Town, triggered a retrospective epidemiological investigation which revealed that sporadic CRE cases had been identified in the institution since 2016. A large retrospective epidemiological study was conducted documenting the emergence and expansion of CRE infection and/or carriage episodes (2016-2020) in patients attending healthcare facilities in the Western Cape Province of South Africa. To contextualise the provincial CRE epidemiological findings, a systematic review was conducted to characterise the burden, distribution, clinical risk factors and outcomes of patients with CRE infection in Africa. Klebsiella spp. predominated, with blaNDM and blaOXA-48-like being the most frequently identified carbapenemases. ST101 and ST147 were most commonly reported in K. pneumoniae, and ST410, ST167 and ST38 in E. coli. Carbapenem resistant strains commonly reported globally, such as K. pneumoniae ST258 and ST307, and E. coli ST131, were less common in Africa. In a retrospective study describing the epidemiology of CRE colonisation and infection among hospitalised patients and outpatients attending Western Cape facilities (2016-2020) we identified 2242 CRE episodes from clinical (1580, 70.5%) and carriage (662, 29.5%) cases. Most patients with clinical CRE infection episodes were located at central hospitals (1570, 70.0%), and Klebsiella spp. (1644, 72.1%) were predominant.. Factors associated with mortality from CRE infection included female sex, adult patients, isolation of CRE from a sterile specimen, and a >3 day interval between hospital admission and specimen collection. The genomic epidemiology of clinical and carriage carbapenem resistant K. pneumoniae (CRKP) from Tygerberg Hospital was described following emergence in 2016 to establishment as an endemic pathogen by 2020. The dominant carbapenemases were blaNDM-1 (201, 48.7%) and blaOXA-181 (194, 47.0%), with co-carriage of blaNDM-1 with blaOXA-181 or blaOXA-232 in 16 isolates (3.9%). Two dominant sequence types, ST39 and ST2621 (each 164, 39.6%), were associated with blaNDM-1 and blaOXA-181 respectively, and had been present since 2016. Interestingly, ST2621-blaOXA-181 was predominantly isolated from adults and clinical isolates, while ST39-blaNDM-1 was associated with neonatal and paediatric populations, and carriage isolates. These strains may be local clones that have acquired carbapenemase genes and become endemic in this setting, in contrast to the intercontinental spread of other successful CRKP lineages. In a subset of CRKP isolates collected at Tygerberg Hospital, we characterised the carbapenemase encoding plasmids using hybrid assembly of short- and long-read whole genome sequencing data. blaNDM-1 was carried on the IncFIB (pQil) plasmid in 8/11 blaNDM-1 positive isolates, with additional resistance genes blaCTX-M15, blaTEM-1 and qnrB1. blaOXA-181 was carried on the ColKP3 (4/8) plasmid with qnrS1, and on the IncC plasmid in 3/8 isolates. The remaining blaOXA-181 was located on the IncX3 plasmid. This doctoral research has generated novel insights into the molecular epidemiology and transmission dynamics of CRE in the Western Cape Province of South Africa and identified patient and pathogen-specific risk factors for CRE infection and clinical outcome. These are important for reinforcing infection prevention and control practices in healthcare facilities, to inform guidelines to limit CRE transmission in resource-limited healthcare settings, and to guide future surveillance efforts. Doctoral 2025-11-10T09:08:43Z 2025-11-10T09:08:43Z 2025-03 Thesis https://scholar.sun.ac.za/handle/10019.1/134313 en Stellenbosch University 153 pages : ill. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Moloto, Kedisaletse Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title | Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title_full | Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title_fullStr | Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title_full_unstemmed | Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title_short | Expansion and clinical impact of emerging carbapenem resistance in the Western Cape of South Africa |
| title_sort | expansion and clinical impact of emerging carbapenem resistance in the western cape of south africa |
| url | https://scholar.sun.ac.za/handle/10019.1/134313 |
| work_keys_str_mv | AT molotokedisaletse expansionandclinicalimpactofemergingcarbapenemresistanceinthewesterncapeofsouthafrica |