Antimicrobial resistance (AMR) is a major threat to public health and the well-being of humans, with high mortality rates of infections caused by MDR GNB. Sub-Saharan Africa (SSA) suffers from a high burden of AMR, but access to adequate microbiological diagnostics for pathogen identification and resistance testing as well as to novel antibiotics that are effective against MDR GNB are scarce. Studies from high-income countries show improved survival of patients with such infections, if novel antibiotics against these pathogens are employed in a targeted manner. However, data from low- and middle-income countries (LMICs) is limited. The purpose of this study is to obtain an accurate picture of the epidemiology of MDR GNB in hospitals in Côte d'Ivoire, Guinea-Bissau and Nigeria, followed by the development and implementation of an evidence-based AMS algorithm, which is coupled to access to antibiotics (i.e. meropenem, ceftazidime-avibactam, cefiderocol and ceftazidime-avibactam + aztreonam) with proven activity against MDR GNB. Taken together, the overall goal is to improve the management of severe infections due to MDR GNB in SSA.
None
Patients with negative blood culture or with detection of Gram-positive bacteria or mycobacteria or fungi in blood culture
Sequential
Treatment according to AMR algorithm
Other interventionIn this study stage, a diagnosis-treatment algorithm that will have been developed based on data collected during study stage 1, will be employed as the intervention to guide the choice of antibiotics active against MDR GNB BSIs. Coupled to the algorithm, a set of specific antibiotics will be made available in the different study settings for treatment of patients with infections due to MDR GNB, for which no equally effective antibiotics are routinely available in the study countries. Previously held discussions with the regulatory agencies in the study countries will feed into the development of the algorithm. The novel treatment options include antibiotics which retain activity in MDR GNB with specific resistance profiles such as ESBL-producing isolates and those with carbapenem resistance. If an antibiotic is not yet licensed in the study country, its use will follow the European Medicines Agency's (EMA) licensing recommendations. The following drugs will be used whenever the causa
Clinical cure
All cause mortality after 14 days after treatment initiation Stage 1 versus Stage 2.
Secondary outcomes
Stage 1 versus Stage 2 Clinical cure Description: Proportion of participants achieving clinical cure within 7 days of inclusion, defined as resolution or significant improvement of signs and symptoms of infection (e.g., fever, hemodynamic instability, organ dysfunction), based on the judgement of the treating physician and, where applicable, the antimicrobial stewardship (AMS) team using a standardized clinical assessment sheet in conjunction with laboratory parameters. Time Frame: Within 7 days after inclusion
Secondary outcomes
Stage 1 versus Stage 2 for all mentioned below: All-cause mortality Description: Proportion of participants who die from any cause within 28 days after inclusion. Time Frame: Day 28
Secondary outcomes
Stage 1 versus Stage 2 Microbiological cure Description: Proportion of participants achieving clearance of bloodstream infection, defined as at least one negative pair of blood culture bottles drawn ≥48 hours after treatment initiation and no subsequent positive blood culture with the same pathogen identified. Time Frame: Up to Day 28
Secondary outcomes
Adherence to the clinical algorithm Description: Proportion of treatment decisions in Stage 2 that are consistent with the study clinical algorithm. Time Frame: During antimicrobial treatment, up to Day 28
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Universität des Saarlandes
Lead sponsor
Swiss TPH, Basel, Switzerland
Collaborator
Institut Pasteur of Cote d'Ivoire
Collaborator
Centre Suisse de Recherches Scientifiques en Cote d'Ivoire
Collaborator
Global Antibiotics Research and Development Partnership
Collaborator
LINQ Management GMBH
Collaborator
Joseph Sarwuan Tarka University Makurdi
Collaborator
Instituto Piaget
Collaborator
Centre for Malaria and other Tropical Disease Care
Collaborator
Obafemi Awolowo University Teaching Hospital
Collaborator
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