Unravelling the complex interplay between antibiotic consumption and adaptive changes in methicillin-resistant Staphylococcus aureus.

OBJECTIVES: This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. METHODS: We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. RESULTS: Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. CONCLUSIONS: In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively.

PROVE-Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia.

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.

Comparative M-protein analysis of Streptococcus pyogenes from pharyngitis and skin infections in New Zealand: Implications for vaccine development.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are responsible for a significant disease burden amongst Maori and Pacific populations in New Zealand (NZ). However, contemporary data are lacking regarding circulating group A Streptococcal (GAS) strains in NZ. Such information is important in guiding vaccine development. METHODS: GAS isolates from April to June 2015 were recovered from skin and pharyngeal samples from children living in areas of high social deprivation in Auckland, NZ, a significant proportion of which are Maori or Pacific. These children are among the highest risk group for developing ARF. Isolates were compared to concurrently collected pharyngeal isolates from Dunedin, NZ, where both the proportion of Maori and Pacific children and risk of developing ARF is low. Emm typing, emm cluster typing and theoretical coverage of the 30-valent vaccine candidate were undertaken as previously described. RESULTS: A high diversity of emm types and a high proportion of emm-pattern D and cluster D4 isolates were detected amongst both skin and pharyngeal isolates in children at high risk of ARF. Pharyngeal isolates from children at low risk of ARF within the same country were significantly less diverse, less likely to be emm pattern D, and more likely to be theoretically covered by the 30-valent M protein vaccine. CONCLUSIONS: The high proportion of emm pattern D GAS strains amongst skin and pharyngeal isolates from children at high risk of ARF raises further questions about the role of skin infection in ARF pathogenesis. Emm types and emm clusters differed considerably between ARF endemic and non-endemic settings, even within the same country. This difference should be taken into account for vaccine development.