Bloodstream Infection Multidrug-resistant Gram-negative Bacteria
Conditions
Keywords
multidrug-resistant gram-negative bacteria, ComBac-Africa
Brief summary
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.
Detailed description
A multicentric, prospective, quasi-experimental study, consisting of two stages, i.e. one observational stage and one interventional stage. The study will be conducted in a total of six hospitals in three countries: Côte d'Ivoire, Guinea-Bissau and Nigeria. During the preparatory phase of this study and before the observational study stage 1 starts, blood culture diagnostics and indications for microbiological sampling will be harmonized across all sites and site feasibility assessments will be conducted. Study stage 1: Antimicrobial susceptibility data of all GNB BSI and detailed assessment of the epidemiology, antimicrobial susceptibility and clinical outcome of MDR GNB in patients with BSIs and their clinical evolution following the standard of care at the individual sites will be collected. Duration: 12 months. Algorithm development: Based on data obtained during stage 1, setting-tailored diagnosis-treatment algorithms that provide guidance on and access to novel antibiotics will be developed. Duration: ≤6 months Study stage 2: Implementation of the clinical diagnosis-treatment algorithm in routine clinical care through AMS teams and evaluation of the effects of the algorithm implementation on mortality, the clinical outcome and microbiological cure. Duration: 12 months.
Interventions
OTHERTreatment according to AMR algorithm
In 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
Sponsors
Universität des Saarlandes
Swiss TPH, Basel, Switzerland
Institut Pasteur of Cote d'Ivoire
Centre Suisse de Recherches Scientifiques en Cote d'Ivoire
Global Antibiotics Research and Development Partnership
LINQ Management GMBH
Joseph Sarwuan Tarka University Makurdi
Instituto Piaget
Centre for Malaria and other Tropical Disease Care
Obafemi Awolowo University Teaching Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Patient with detection of a presumed multidrug-resistant Gram-negative bacterium (MDR GNB), identified by growth on MDR screening agar, in ≥1 blood culture bottle. Provision of written informed consent by the patient or the patient's parent(s)/legal representative(s).
Exclusion criteria
* Patients with negative blood culture or with detection of Gram-positive bacteria or mycobacteria or fungi in blood culture Patients with GNB in blood culture that are not resistant to third-generation cephalosporins (ceftriaxone or cefotaxim) or carbapenems (meropenem) Patients with polymicrobial infection Patients with GNB detected in blood cultures and without systemic infection signs, in whom the microbiological finding is unambiguously interpreted as contamination not necessitating antimicrobial treatment Patient already recruited for concurrent participation in other clinical studies or trials Patients with known anaphylactic reactions or severe hypersensitivity to beta-lactam antibiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure | 14 days | All cause mortality after 14 days after treatment initiation Stage 1 versus Stage 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcomes | 28 days | 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 |
Contacts
CONTACTSören L Becker, Prof. Dr. Dr.
CONTACTJacqueline Rehner, Dr.
STUDY_CHAIRAaron O Aboderin, Prof. Dr.
Obafemi Awolowo University Nigeria
Outcome results
None listed