The Emerging Resistance Surveillance for Priority Bacterial Pathogens project monitors priority, unusual, and emerging resistance in clinically important bacterial pathogens, particularly carbapenem-resistant Enterobacterales with no carbapenemase detected and resistance mechanisms relevant to WHO AWaRe Reserve antibiotics in ESKAPEE pathogens. Public and private routine diagnostic laboratories are encouraged to contact CHARM when they identify unusual, unexplained, or concerning resistant organisms. Referred isolates undergo confirmatory susceptibility testing, followed by whole genome sequencing where appropriate, to determine the likely mechanism of resistance and support surveillance, outbreak detection, antimicrobial stewardship, infection prevention and control, and national AMR policy.

Invasive mould infections (IMIs) are serious fungal infections that affect normally sterile parts of the body (e.g. kidneys, brain, bloodstream). They mainly occur in immunocompromised or critically ill patients and are associated with high illness and death rates. Due to limited data and diagnostic challenges, the true burden of these infections in South Africa is not well understood.

The programme aims to describe the epidemiology, patient characteristics, clinical management, outcomes, and antifungal resistance patterns of IMIs, as well as to explore the molecular characteristics of the causative organisms over a 2 year period. It uses a nationwide, laboratory-based approach to collect data from hospitalized patients nested under GERMS-SA.

A case is defined as a hospitalized patient with a laboratory-confirmed mould infection, identified by culture from a normally sterile site or from specific specimens such as bronchoalveolar lavage (for Aspergillus) or corneal scrapings, with repeat positive tests within 30 days considered part of the same case and yeast infections are excluded.

We plan to collect mould isolates identified by the diagnostic laboratories at all GERMS-SA enhanced surveillance sites and private laboratories, from patients suspected of invasive fungal infections. Clinical information will be collected by the surveillance officers using a standardised case report form and limited data from the private sector laboratories will be shared by the clinical and laboratory team.

We will confirm identification of the isolates using either phenotypic or genotypic methods and perform antifungal susceptibility testing on confirmed isolates using the EUCAST method after verification of the method. Whole genome sequencing will be performed on selected isolates with low or high MIC and those difficult to identify using both phenotypic and molecular metho

Overall, the initiative aims to strengthen epidemiological understanding, improve diagnostics and patient management, and inform public health responses to these life-threatening infections.

Candidaemia is a bloodstream infection caused by Candida species. It is a major cause of morbidity and mortality in healthcare settings. Considered the fourth most common bloodstream infection. Surveillance plays a critical role in understanding its epidemiology, guiding treatment, and informing infection prevention strategies.

Candidaemia surveillance is conducted through the GERMS-SA platform, a national, laboratory-based surveillance system for antimicrobial resistance and priority pathogens. The programme collects data from public and private sector laboratories across  South Africa.

This project aims to monitor national incidence and species distribution of candidaemia by performing  enhanced surveillance at three  public sector laboratories-Helen Joseph,Chris Hani Baragwanath and Charlotte Maxeke Hospitals as well as  a laboratory based surveillance at two private sector facilities namely Donald Gordon and Milpark Hospitals.

A case will be defined as a hospitalised adult patient with laboratory-confirmed Candida species isolated from blood cultures with repeat positive tests from the same patient within 30 days considered part of the same case.

Isolates received at NICD from the diagnostic laboratories will undergo confirmatory identification and antifungal susceptibility testing. A subset of isolates will be subjected to whole genome sequencing to characterise genotypic resistance patterns.

Overall, the project aims to achieve public health impact by supporting development of national treatment and prevention guidelines as well as strengthening antifungal stewardship programs.

The project outlines a comprehensive evaluation of cefiderocol susceptibility testing methods for multidrug-resistant Gram-negative pathogens of clinical importance. Cefiderocol was added to the WHO Essential Medicines List due to its unique mechanism of action, based on entering bacterial cells using active iron transporters and is included in the WHO AWaRe (Access, Watch, and Reserve) Handbook as a “Reserve” antibiotic. The study will determine the in vitro activity of cefiderocol against carbapenem-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia using disk diffusion, manual broth microdilution, ComASP®, and UMIC® methods.

The performance of the commercially available methods—assessed through accuracy, categorical agreement, and essential agreement—will be compared against the manual broth microdilution reference panel, using both prospective clinical isolates and archived South African isolates in accordance with the South African Health Technology Assessment requirement. Precision testing will evaluate inter-run, inter-user, day-to-day, and inter-batch reproducibility across methods. Whole-genome sequencing will be performed on clinical isolates that are cefiderocol-resistant by phenotypic reference testing method (BMD) to identify genetic determinants and mechanisms associated with resistance.

The study setting is at the Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses (CHARM) at NICD, who provide isolates from the National Stock Culture Collection (NSCC) Repository located at CHARM and from prospectively collected isolates from NHLS laboratory sites in Gauteng. Estimated timeline was January to December 2026.

Carbapenem-resistant Enterobacterales (CRE) are a group of gram-negative bacteria that are resistant to carbapenem antibiotics, last line class of antibiotics generally reserved for severe infections. These includes organisms such as Klebsiella spp, Escherichia coli, Enterobacter spp, Serratia spp, Citrobacter spp, etc. They pose a significant public health threat as they cause healthcare-associated infections are linked with major outbreaks in healthcare facilities and are difficult to treat because of limited remaining antimicrobial treatment options. Infections caused by CRE’s includes pneumonia, bloodstream infections, urinary tract infections (UTIs), wound infections and meningitis. Given the growing threat of CRE infections, World Health Organism has categorized CRE’s as a critical-priority group of pathogens urgently needing new drugs. Infections caused by Carbapenem-resistant Enterobacterales are associated with high rates of morbidity, mortality, and high healthcare costs. Wastewater surveillance has emerged as a valuable tool in monitoring antimicrobial resistance and it supports the One-Health approach that recognizes the interdependence of human, animal and environmental health and tackles antimicrobial resistance (AMR) in a multifaceted manner.

Therefore, the wastewater surveillance for CRE is conducted concurrently with CRE clinical surveillance. This project aims to identify and determine the prevalence of carbapenem-resistant enterobacterales and antibiotic resistance genes conferring resistance to carbapenems. The project is nested within wastewater surveillance project currently on-going at the centre for Vaccine and Immunology (CVI). Wastewater samples are thus collected from CVI. The samples are collected from all 9 provinces in South Africa in various collection sites. This is a short-term project conducted over a period of six months (from November 2024 – April 2025). The surveillance involves collection and analysis of samples originating from treatment facilities, hospitals, agricultural runoff and community settings. The surveillance will shed light on organisms that may be missed in clinical surveillance alone. Wastewater surveillance is efficient and has great potential for early warnings of transmission and outbreaks of infectious disease. It provides real-time information on what is happening at a population level.

Invasive candidiasis (IC) remains a serious global health challenge, with high mortality rates despite treatment, particularly in regions like South Africa where healthcare systems are burdened by factors such as HIV and limited access to antifungals. Antifungal resistance, especially in non-albicans Candida species, has become a growing issue, further complicating management. Existing research on IC is largely conducted in high-income settings, leaving gaps in understanding the specific dynamics of antifungal resistance, Candida colonisation, and transmission patterns in low- and middle-income countries (LMICs).

This study is nested within a multi-centre, prospective cohort study which aims to explore the relationship between antifungal use and the development of resistance in Candida species among ICU patients in four major hospitals in Johannesburg, South Africa and Mozambique. The primary hypothesis posits that systemic antifungal use in the ICU setting influences local fungal ecology and drives resistance development, leading to colonisation and infection with less susceptible strains. Additionally, the study will investigate whether invasive candidiasis arises from the colonizing flora, particularly focusing on how skin and gut mycobiota serve as reservoirs for invasive infection.

The study comprises three key components:

1. Surveillance of Candida colonisation and candidaemia over a period of 6-12 months
2. A unit-wide antifungal consumption tracking,
3. An evaluation of antifungal stewardship (AFS) and infection prevention and control (IPC) practices.

Over 6-12 months, 800-1000 ICU patients will be enrolled, with serial swabs and blood cultures conducted to assess colonisation, species distribution, and resistance development. Environmental sampling and whole-genome sequencing will aid in understanding transmission dynamics, while detailed antifungal prescription data will be analyzed to evaluate stewardship practices. Antifungal consumption will be tracked longitudinally, providing insights into usage patterns and trends across hospital units.

The primary outcome of the study will be the incidence rate of resistance emergence in colonising or invasive Candida isolates in patients exposed to antifungal agents. Secondary outcomes include rates of colonisation and candidaemia with resistant species, the emergence of resistance-associated genetic mutations, and changes in Candida species distribution. This study will also assess gaps in IPC and antifungal stewardship, providing a foundation for targeted interventions to reduce antifungal resistance and improve patient care.

By generating setting-specific data on Candida colonisation, resistance patterns, and antifungal use, this study will contribute valuable insights to guide antifungal stewardship and infection control programs in South African ICUs. These findings will support the development of tailored national and regional guidelines to optimize antifungal use, improve patient outcomes, and reduce the burden of antifungal resistance.

The current running project at the NICD is the Carbapenemase-Resistant Enterobacterales (CRE) and Enterobacter cloacae complex (ECC) surveillance project. This project aims at monitoring, understanding, and mitigating the spread of CRE infections in healthcare settings. These bacteria have developed resistance, over time, to carbapenems, an effective class of antibiotics that represent the last line of treatment against serious infections. These infections confer a very serious public health risk, as limited options for their treatment are related to high morbidity and mortality rates, especially among vulnerable populations. Surveillance activities are nested under GERMS SA, and it is given enhanced collection of demographics, clinical and epidemiological data collection. Enterobacter cloacae complex has not previously been studied as part of national surveillance in South Africa. As such, prevalence, antimicrobial susceptibility and genomic profiles are important to determine.

Key activities involve laboratory testing and analysis. Each sample received undergoes additional laboratory testing with bacterial identification and antibiotic susceptibility testing, the molecular testing. The CRE Surveillance Project enables infection surveillance with data generated to allow for the early detection of outbreaks. It builds capacity for managing the problem of CRE through training and technical assistance, thereby enhancing the capacity for ongoing infection control to meet the goals of preparedness and resilient health systems.

We expect that tracking and managing CRE infections reduces the infection rate burden and results in reduced morbidity and mortality, which in turn leads to improvements in patient health outcomes. Data-driven infection control practices enhance quality of care, promote a safer healthcare environment, and facilitate equity in access to quality care-all elements of patient-centered goals.

This insightful surveillance data will inform long-term public health policy and ensure proper, sustainable infection control practices. It equips healthcare providers with knowledge and tools to take appropriate case management actions for the durability of CRE and aligns with RISE’s mission of sustainable health system strengthening. This project is supported by Reaching Impact, Saturation, and Epidemic Control (RISE) program under GHSA under USAID and NICD.