Erkison Odih: Genomic epidemiology of Acinetobacter baumannii

THE PROJECT
Acinetobacter baumannii, formerly thought of as an environmental species, has become one of the most important Gram-negative pathogenic bacteria in healthcare settings globally. A. baumannii causes a variety of infections mostly in immunocompromised patients and in patients whose clinical care require invasive medical procedures such as mechanical ventilation and catheterization. These infections are often difficult to treat due to increasing rates of resistance to antimicrobials, thus leading to high mortality rates of up to 80%.

Their clinical significance stems from these increasing resistance rates to the available therapeutic options, including the carbapenems, as well as their capacity to persist in hospital environments and cause life-threatening infections in vulnerable patients. Reported carbapenem resistance rates for A. baumannii exceed 70% in many regions of the world, with this increase in prevalence fueled primarily by the dissemination of genes encoding carbapenem-hydrolyzing enzymes, particularly the oxacillinases (OXA) and New Delhi metallo-beta-lactamases (NDM).

These genes are often carried on mobile genetic elements, thus facilitating their frequent transfer and acquisition. The acquisition of carbapenemase genes is also associated with the rapid expansion and dissemination of resistant lineages, with certain international clones (ICs 1 - 9), each with high carbapenem resistance rates, accounting for a majority of the A. baumannii problem worldwide. Prior to this study, carbapenem-resistant A. baumannii causing clinical infections were sparsely reported in Nigeria, and the prevalent lineages and carbapenem resistance burden were unknown.

PURPOSE
This project was conducted to determine the epidemiology of A. baumannii infections in Nigeria and characterize the clinically relevant lineages and burden of carbapenem resistance using whole genome sequencing. Clinical A. baumannii isolates from invasive infections and suspected outbreaks across hospitals and laboratories in southwestern Nigeria were characterized. Hospital wastewater samples were also collected over a one-year period and characterized using whole genome sequencing to investigate the potential contribution of hospital wastewater to the dissemination of A. baumannii via the environment in Nigeria.

RESULTS
This thesis demonstrated the widespread presence of carbapenem-resistant A. baumannii in Nigeria, revealing diverse strains in clinical settings and the environment, many of which were novel and emergent lineages. Carbapenem resistance rates were high among the clinical and environmental A. baumannii isolates. The blaOXA-23 and blaNDM-1 carbapenemase genes were highly prevalent in both the clinical and environmental strains, and there is huge potential for their continued dissemination due to their association with highly mobilisable mobile genetic elements. Given the likelihood of underreporting in Nigerian hospitals, urgent action is needed to improve the laboratory detection and surveillance of this and other important pathogens in Nigerian healthcare settings. The implementation of active surveillance and stringent infection prevention and control policies will also be crucial to limit the spread of carbapenem-resistant A. baumannii within hospitals.

 This thesis also demonstrated that access to real-time whole-genome sequencing is essential for A. baumannii outbreak source attribution and effective control. Broader epidemiological efforts are necessary to understand both intra- and extra-hospital factors driving the spread of these carbapenem-resistant strains. In this study, carbapenem-resistant A. baumannii strains were constantly being released via hospital wastewater into the environment. This warrants the implementation of preventive measures and further research to assess and quantify the human health risks posed by A. baumannii dissemination via contaminated environmental sources. The findings of this study emphasize the value of genomic epidemiological surveillance using a One Health approach to aid tailored strategies to curb pathogen spread within and beyond healthcare settings.

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