Browsing by Author "Eley Brian"

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    A descriptive study of vancomycin usage at Red Cross War Memorial Children's Hospital, Cape Town
    (2023) Greybe, Leonore; Nuttall, James; Eley Brian
    Background: Antimicrobial stewardship principles guide the clinical use of vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). Methods: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy/1000 patient days (IQR 38–72). The median starting dose was 15 mg/kg/dose (IQR 14 ̶ 15) and median daily dose was 45 mg/kg/day (IQR 43–60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group was longer than the empiric group (p=0.001). Only 65/98 (66%) episodes where vancomycin treatment exceeded three days had vancomycin serum trough concentrations performed, and only 16/65 (25%) of these samples were obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with gram positive bacteria on culture (OR 1.02, 95% CI 0.17 ̶ 4.2). Conclusion: Prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: Our study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.
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    Burden and causes of ongoing paediatric infectious disease morbidity and mortality in the Western Cape Province of South Africa
    (2025) Kehoe, Kathleen; Davies, Mary-Ann; Eley Brian
    Under-five mortality has significantly decreased globally over the past 28 years, halving to 39 deaths per 1,000 live births in 2018, yet remains high, necessitating further progress to meet the Sustainable Development Goal of reducing it to below 25 deaths per 1,000 live births by 2030. Improvements in healthcare access, nutrition, vaccinations, and socioeconomic conditions have been key drivers of this observed reduction, but infectious diseases such as lower respiratory tract infections (LRTIs) including pneumonia, diarrhoea, and malaria continue to cause substantial childhood mortality. In South Africa, LRTIs, diarrhoea, meningitis, and tuberculous meningitis (TBM) remain leading causes of childhood morbidity and mortality. The Western Cape continues to bear a substantial burden from these infectious diseases, but the available data is outdated and lacks granularity. Therefore, the aim of this thesis was to explore the morbidity and mortality of LRTIs, diarrhoea, meningitis and TBM among children younger than five years in the public sector in the Western Cape. After a brief background chapter which lays out the key issues and overview of the South African healthcare system, Chapter 2 provides a comprehensive literature review discussing the morbidity and mortality of LRTIs, diarrhoea and meningitis (including TBM where appropriate) in children under five years globally and in South Africa with a focus on the Western Cape. Chapter 3 provides a detailed description of the data management required to develop the de-duplicated dataset that was used for each of the results chapters (Chapter 4-7). Chapter 4 explores causes of death using various death data sources, including routinely collected and detailed audits, and found that routine hospital information systems had accurate causes of death relying on International Classification of Diseases 10th Revision codes, particularly for LRTIs and diarrhoea. Chapters 5 and 6 explore the impact of COVID-19 public health and social measures (PHSM) on LRTI and diarrhoea admissions. COVID-19 surges and their associated measures, including PHSM, were linked to declining LRTI admissions and in- facility deaths, likely driven by a combination of reduced infectious disease transmission and reduced use of healthcare services. Lastly, Chapter 7 identified associations with repeat infectious disease admissions (LRTIs, diarrhoea and meningitis) among children who were first admitted for an infectious disease in the first six months of life. Male children with lower birthweight, whose first admission was due to LRTI or diarrhoea (versus meningitis), experienced a longer length of stay during their initial admission, and were living with HIV were more likely to be re-admitted for an infectious disease. Both individual- and population level interventions are needed to reduce the prevalence and impact of factors associated with infectious disease re-admissions and reduce infectious disease morbidity. This thesis concludes that infectious disease morbidity and mortality persist among children under five years in the Western Cape by presenting up-to-date and comprehensive data. It highlights the need to address existing gaps to improve data quality and comprehensiveness, as well as healthcare and health outcomes for these children.
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    Neuropsychiatric complications of efavirenz in children with HIV-1 infection
    (2018) Hammond Charles; Eley Brian
    Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition is unknown. Genetically determined black South Africans who are slow metabolizers of efavirenz may be at risk of toxicity. This study describes neuropsychiatric and neurocognitive manifestations of South African children with suspected efavirenz neurotoxicity. Method: This retrospective study describes clinical features of 12 children with suspected efavirenz neurotoxicity (2008 – 2014). Results: Twelve children were referred (aged 3 years 4 months to 12 years, mean 7 years 8 months; 8 indigenous African (black) and 4 mixed ancestry). Six had acute neuropsychiatric manifestations after 2-8 weeks (mean 5 weeks) on efavirenz including drowsiness, seizures, sleep disturbances, behavioural changes, ataxia and slurred speech. Symptoms resolved over a few weeks in four. Two black children were phenotypically slow metabolizers with high plasma efavirenz concentrations above normal range resulting in discontinuation of efavirenz. Nine children had neurocognitive concerns potentially exacerbated by long-term efavirenz (6-72 months therapy; mean 31 months), and showed poor performance in all neurocognitive domains. Conclusion: Efavirenz causes transient neuropsychiatric adverse effects and may contribute to poor longterm neurocognitive outcomes in HIV-infected children. Genetically slow metabolizers are at risk of neurotoxicity. Prospective studies comparing efavirenz-treated and efavirenz-naïve children are needed.