Combating Multidrug-resistant Gram-negative Bacteria in Africa Through Diagnostic and Antimicrobial Stewardship (ComBac)

Combating Multidrug-Resistant Gram-Negative Bacteria in Africa Through Diagnostic and Antimicrobial Stewardship: A Multicentre, Prospective Quasi-experimental Two-stage Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Bloodstream Infection Multidrug-resistant Gram-negative Bacteria
• Intervention / Treatment: Other: Treatment according to AMR algorithm

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.

• Study Type: Interventional
• Enrollment (Estimated): 1320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sören L Becker, Prof. Dr. Dr.; Phone Number: +4968411623900; Email: soeren.becker@uks.eu
• Study Contact Backup: Name: Jacqueline Rehner, Dr.; Phone Number: +4915754996344; Email: Jacqueline.Rehner@uks.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Treatment according to AMS algorithm; There is no real separation into arms. Everyone will receive the applicable treatment. It is quasi-experimental.

Other: Treatment 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure	All cause mortality after 14 days after treatment initiation Stage 1 versus Stage 2.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days
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	28 days
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	28 days
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	28 days
Secondary outcomes	Appropriateness of antimicrobial therapy Description: Proportion of participants receiving antimicrobial therapy deemed appropriate according to pathogen susceptibility results and study treatment guidelines. Time Frame: Up to Day 28	28 days
Secondary outcomes	MDR pathogen-specific mortality Description: Proportion of participants with bloodstream infection caused by multidrug-resistant Gram-negative bacteria who die within 28 days. Time Frame: Day 28	28 days
Secondary outcomes	Adverse event profile of study antimicrobials Description: Incidence and severity of adverse events associated with meropenem, ceftazidime-avibactam, cefiderocol, and ceftazidime-avibactam plus aztreonam, as applicable. Time Frame: Up to Day 28	28 days
Secondary outcomes	Clonality of MDR Gram-negative bloodstream isolates Description: Genetic relatedness of multidrug-resistant Gram-negative bacterial strains isolated from bloodstream infections at participating hospitals, assessed by molecular typing methods. Time Frame: During study period and analysis of collected isolates	28 days

Collaborators and Investigators

• Sponsor: Universität des Saarlandes
• Collaborators: Obafemi Awolowo University Teaching Hospital; Global Antibiotics Research and Development Partnership; Instituto Piaget; Centre Suisse de Recherches Scientifiques en Cote d'Ivoire; LINQ Management GMBH; Institut Pasteur of Cote d'Ivoire; Swiss TPH, Basel, Switzerland; Joseph Sarwuan Tarka University Makurdi; Centre for Malaria and other Tropical Disease Care
• Investigators: Study Chair: Aaron O Aboderin, Prof. Dr., Obafemi Awolowo University Nigeria

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2027
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: September 9, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: multidrug-resistant gram-negative bacteria; ComBac-Africa
• Other Study ID Numbers: ComBac-AfricaClinicalTrial; Project 101190791 (Other Identifier: EDCTP3)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No