The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

Candida auris has been detected at almost 100 South African hospitals, causing large outbreaks in some facilities, and this pathogen now accounts for approximately 1 in 10 cases of candidaemia. The objective of this guideline is to provide updated, evidence-informed recommendations outlining a best-practice approach to prevent, diagnose and manage C. auris disease in public- and private-sector healthcare settings in South Africa. The 18 practical recommendations cover five focus areas: laboratory identification and antifungal susceptibility testing, surveillance and outbreak response, infection prevention and control, clinical management and antifungal stewardship.

Background: Candidemia is associated with high morbidity and mortality. The epidemiology of candidemia has changed globally over the past 20 years. South African surveillance demonstrated a shift in epidemiology from Candida albicans to non-albicans species including Candida parapsilosis and Candida auris. Hospital-level candidemia incidence from South Africa has not been reported previously. Methods: We performed a retrospective laboratory-based analysis of blood cultures with confirmed causative agents of candidemia. Ward type, department, gender and admission to critical care units were captured. Data were analysed in Microsoft Excel, Statistical Package for the Social Sciences (SPSS) and Epitools. Results: The incidence of candidemia during the study period was 2.87 per 1000 admissions. The total proportion of non-albicans species causing candidemia was 425/618 (69.7%). Overall, 65.4% of candidemia cases occurred in non-critical care units. There was a significant increase in the proportion of C. auris isolates between 2016 and 2020 (p < 0.001). Isolation of C. auris was associated with admission to critical care units (p < 0.001, odds ration [OR] 3.856, 95% confidence interval [CI]: 2.360–6.300). The proportion of azole-resistant candidemia cases increased from 21/53 (39.6%) in 2016 to 41/59 (69.5%) in 2020 (p = 0.002). Conclusion: The incidence of candidemia remained stable over the five-year study period. However, the proportion of C. auris isolates increased significantly during the study period as did the overall proportion of azole-resistant candidemia. Antifungal stewardship and continued hospital-level surveillance are imperative.