Multi-Drug Resistant Gram-Negative bacterial bloodstream infection
Conditions
Interventions
Treatment
Diagnostic
Sponsors
Saarland University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient with detection of a presumably MDR GNB (identified by growth on MDR screening agars or phenotypic resistance to ceftriaxone or meropenem) in =1 blood culture bottle Provision of written informed consent to participate in the study by patient or her/his parents/legal (or legally acceptable) representative(s). In severely ill patients, an emergency consenting procedure will be implemented as an alternative for regular consenting. In addition to the legal guardian’s written consent, oral or written assent will be sought from children aged 6-11 years and 12-17 years, respectively. Age-appropriate assent forms will be used. For neonates and critically ill infants, enrolment will be subject to additional review by the site principal investigator to ensure minimal risk and clear clinical justification. Capability of the patient or her/his parents/ legal representative(s) to understand the purpose and risks of the study, as judged by the recruiting physician
Exclusion criteria
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 carbapenems (meropenem) Patients with polymicrobial bloodstream infection (defined as isolation of =2 clinically significant microorganisms from blood cultures obtained within the same infectious episode; does not apply when additional organisms are considered likely contaminants rather than true pathogens (e.g. Staphylococcus epidermidis in a single bottle)) 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 Patients already recruited for concurrent participation in other clinical studies or trials Patients with known anaphylactic reactions or severe hypersensitivity to beta-lactam antibiotics Participants in whom initial screening suggests MDR GNB (growth on MDR screening agars or phenotypic resistance to ceftriaxone or meropenem), but confirmatory testing reveals susceptible organisms (GNB in blood culture that are not resistant to ceftriaxone or meropenem), will be considered post-enrolment exclusions. In stage 2, these participants will be followed for a further 24 hours for safety reasons, but will be otherwise excluded from the study. As they will not contribute to the study population, they will be replaced by another participant. In stage 1, safety reporting in participants excluded post-enrolment will depend on the national requirements in the study countries
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All-cause mortality at 14 days after enrolment in patients with MDR GNB BSIs (stage 2 vs. stage 1) | — |
Secondary
| Measure | Time frame |
|---|---|
| All-cause mortality at 14 days after enrolment ; Clinical cure within 7 days +/- 1 day of enrolment (clinical cure is defined as resolution or significant improvement of signs and symptoms of infection (e.g. fever, hemodynamic instability, organ dysfunction)), based on judgement of the responsible clinical investigator using a standardized clinical assessment sheet, in conjunction with laboratory parameters (stage 2 vs. stage 1) Microbiological cure (defined as clearance of bloodstream infection in follow-up blood cultures, i.e. =1 negative blood culture bottle(s) drawn =48 hours after enrolment and no further positive blood culture with the same pathogen identified) (stage 2 vs. stage 1) Adherence to the clinical algorithm by the treating physician(s) in stage 2 Appropriateness of antimicrobial therapy in both study stages All-cause mortality, stratified by pathogen (stage 2 vs stage 1) Adverse event profile of meropenem, ceftazidime-avibactam, cefiderocol and ceftazidime-avibactam plus aztreonam, as applicable (stage 2) Clonality of MDR GNB strains isolated from BSIs at the hospital level (stages 1 and 2 combined) Absolute number and distribution of MDR GNB in patients with BSIs (stages 1 and 2 combined) ;All-cause mortality at 28 days after enrolment (stage 2 vs. stage 1) | — |
Countries
Cote Divoire, Guinea-Bisseu, Nigeria
Contacts
Public ContactJulia Buech
Communication LINQ Management GmbH
Outcome results
None listed