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Antimicrobial resistance must be recognised as a global societal priority - even in the face of the worldwide challenge of the COVID-19 pandemic. COVID-19 has illustrated the vulnerability of our healthcare systems in co-managing multiple infectious disease threats as resources for monitoring and detecting, and conducting research on antimicrobial resistance have been compromised during the pandemic. The increased awareness of the importance of infectious diseases, clinical microbiology and infection control and lessons learnt during the COVID-19 pandemic should be exploited to ensure that emergence of future infectious disease threats, including those related to AMR, are minimised. Harnessing the public understanding of the relevance of infectious diseases towards the long-term pandemic of AMR could have major implications for promoting good practices about the control of AMR transmission.

Objectives: This study delineated the clonal lineages, antibiotic resistome and plasmid replicon types in multidrug-resistant K. pneumoniae isolates from a teaching hospital in Ghana. Methods: Identification and antibiotic susceptibility testing were done using the MALDI-TOF MS and Vitek-2 automated system. Genomic DNA extraction was carried out using the NucliSens easyMAG® (BioMérieux) kits and the DNA was subjected to whole genome sequencing (WGS) using the Illumina MiSeq platform. Results: Of the 200 isolates obtained, 37 were identified as K. pneumoniae of which 9 were resistant to all second and third-generation cephalosporins. These 9 isolates selected for further genomic analysis were characterized by the presence of 8 diverse sequence types (STs), capsular polysaccharide serotypes (K types and wzi allelic types) and multiple genes encoding resistance to β-lactams (blaCTX-M-15, blaSHV-11, blaTEM-1B, blaOXA-1), aminoglycosides (aac(3)-IIa, strB, strA, aadA16), fluoroquinolones/quinolones (qnrB66, oqxA, oqxB) and other antibiotic classes. Resistance genes were associated with plasmids, predominantly IncFIB(K) and ColRNAI. Multiple and diverse mutations in quinolone resistance-determining regions of gyrA (S83Y, D87A) and parC (S80I, N304S) in isolates resistant to ciprofloxacin (MIC ≥ 4 mg/mL) were found. Global phylogenomic analysis affirmed the diverse clonal clustering and origin of these isolates. Conclusions: The varied clonal clusters and resistome identified in the multidrug-resistant K. pneumoniae isolates is a major threat to the management of infections in Ghana. The molecular characterization of antibiotic resistance is thus imperative to inform strategies for containment. Keywords: Whole genome sequencing, Multidrug-resistant, ESBL, Klebsiella pneumoniae, Resistome, Ghana

The Global Action Plan on antimicrobial resistance calls for the use of antimicrobial medicines in human and animal health to be optimized, in tandem with a strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data for African countries such as South Africa. Determining antimicrobial consumption data in low-resource settings remains a challenge. This article describes alternative mechanisms of assessing antimicrobial consumption data, such as the use of Intercontinental Marketing Services (IMS) data and contract data arising from tenders (an open Request for Proposal, RFP), as opposed to the international norms of daily defined doses per 100 patient-days or per 1000 population. Despite their limitations, these serve as indicators of antimicrobial exposure at the population level and represent an alternative method for ascertaining antimicrobial consumption in human health. Furthermore, South Africa has the largest antiretroviral treatment programme globally and carries a high burden of tuberculosis. This prompted the inclusion of antiretroviral and anti-tuberculosis antibiotic consumption data. Knowledge of antimicrobial utilization is imperative for meaningful future interventions. Baseline antimicrobial utilization data could guide future research initiatives that could provide a better understanding of the different measures of antibiotic use and the level of antibiotic resistance. Keywords: Antimicrobial governance, DOTS, Antibiotic consumption, Developing country, Antimicrobial exposure

Background: The One Health approach is a global strategy that encourages interdisciplinary collaboration on health at the human–animal–environmental interface. Antibiotic resistance is a direct consequence of the selection pressure from antibiotic use in humans, animals, and the environment, requiring a One Health approach towards its containment. The high HIV/AIDS burden and other risk factors for communicable diseases in South Africa results in a high incidence of infectious diseases, engendering extensive antibiotic use and subsequent resistance. Two-thirds of the antimicrobials sold for animal use are used in growth promotion. Although the burden of antibiotic resistance has not been quantified, available evidence indicates that it is escalating in humans, animals, and the environment. There is thus a need to quantify the burden of antibiotic resistance with a view to implementing measures for its containment on biomedical, clinical, sociobehavioural, drug discovery/diagnostics, and policy grounds. Methods: This project delineates the molecular epidemiology, nature, and extent of antibiotic resistance in the One Health context in the uMgungundlovu District in KwaZulu-Natal, South Africa. The aim is to map the fluidity of antibiotic-resistant bacterial clones, antibiotic resistance genes, and their associated mobile genetic elements within and between the human, animal, and environmental health sectors by (1) instituting surveillance programmes on antibiotic use and resistance in human, animal, and environmental health; (2) demonstrating the phenotypic and genotypic mechanisms of antibiotic resistance by sensitivity testing and appropriate screening tests and whole-genome sequencing; and (3) establishing the clonality and genetic determinants of resistance by multi-locus sequence typing and whole-genome sequencing. Findings: This project began in 2017. Isolates have been collected from patients, chicken, water, and soil. The molecular epidemiology of their antibiotic resistance profiles will be determined. The project will (1) provide a proxy surveillance system for antibiotic resistance in humans and food animals and (2) unambiguously give credence to the One Health approach for the containment of antibiotic resistance mooted in the UN General Assembly Political Declaration on Antimicrobial Resistance and by the tripartite alliance of the WHO, the Food and Agriculture Organization, and the World Organisation for Animal Health using a specific conceptual framework. Interpretation: Successful proof of concept will require validation of the conceptual framework in different countries and health systems with different levels of antibiotic resistance and will thus be tested in high-income, middle-income, and low-income countries with different antibiotic resistance burdens. Funding: South African National Research Foundation, South African Medical Research Council.