Combating Multidrug-Resistant Gram-Negative Bacteria in Africa Through Diagnostic and Antimicrobial Stewardship: A Multicentre, Prospective Quasi-experimental Two-stage Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,320
- 主要终点
- Clinical cure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
Treatment according to AMS algorithm
There is no real separation into arms. Everyone will receive the applicable treatment. It is quasi-experimental.
干预措施: Treatment according to AMR algorithm (Other)
结局指标
主要结局
Clinical cure
时间窗: 14 days
All cause mortality after 14 days after treatment initiation Stage 1 versus Stage 2.
次要结局
- Secondary outcomes(28 days)