Clinical trial NCT04850677: Treating Non-typhoidal Salmonella Bloodstream Infections in Children Under Five in DR Congo: a Cohort Study
Official title: Treating Non-typhoidal Salmonella Bloodstream Infections in Children Under Five in DR Congo: a Cohort Study - TreNTS
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Blood-stream Infections
Salmonella Infection Non-Typhoid
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
name: Hôpital St. Luc Kisantu
name: KU Leuven
name: International Vaccine Institute
First posted: 2021-04-20
Enrollment: 1884
Sex: ALL
Minimum age (years): 28
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children between 28 days and 5 years that are admitted to the Kisantu hospital with a need for a blood sample culture (suspicion of a blood-stream infection).

Brief summary: With this study the researchers aim to provide observational data on the treatment efficacy of currently used antibiotic treatment regimens for NTS BSI in hospital-admitted children. The study is an observational cohort study where the antibiotic treatments used and treatment outcomes in the St. Luc general referral hospital in Kisantu health zone (Province Kongo Central, DR Congo) will be described.

Detailed description: In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are a frequent cause of bloodstream infection (BSI) in young children, display high levels of antibiotic resistance and have a high case fatality rate (15%). In Kisantu hospital in the Democratic Republic of Congo (DR Congo), NTS account for 75% of blood culture pathogens in young children.

Currently, NTS BSI are mostly treated with third generation cephalosporins or fluoroquinolones. However, resistance to these antibiotics is emerging in NTS BSI. Third generation cephalosporine and fluoroquinolone resistant Salmonella are identified as critical priority pathogens by the World Health Organization (WHO). To combat the developing antimicrobial resistance, rational and evidence-based antibiotic treatment of NTS BSI is crucial.

So far, there are no guidelines to treat NTS BSI in a low-resource setting. The currently used antibiotic regimens are experience-based or extrapolated from typhoid fever. The absence of dedicated studies addressing antibiotic treatment efficacy in NTS BSI in sub-Saharan African children hampers the development of evidence-based antibiotic treatment guidelines and antibiotic stewardship.

Clinical practice guidelines established for high- and middle-income countries recommend 7 - 14 days of parenteral antibiotic treatment for NTS BSI. In sub-Saharan Africa however, financial, logistic and nursing care barriers preclude such long parenteral treatment regimens.

To decrease the case fatality and combat antibiotic resistance of NTS BSI in its most affected population (i.e. children in sub-Saharan Africa), data that support appropriate antibiotic treatment (i.e. antibiotic class, dose, route and duration) are urgently needed.

The researchers aim to provide observational data on the treatment efficacy of currently used antibiotic treatment regimens for NTS BSI in hospital-admitted children.

They hypothesize that, in terms of treatment efficacy in hospital admitted children with NTS BSI, a short course of parenteral antibiotics (\<7 days) with switch to oral antibiotics is not inferior to a full parenteral antibiotic course (≥7 days).

This study is designed as a prospective, single-center, hospital-based observational study on the efficacy of antibiotic treatment of a cohort of young children (1 month to 5 years old) with NTS BSI. Data will be collected from the enrolled children during three different study phases, i.e., upon admission, daily in-hospital follow-up and post-discharge follow-up.

Eligibility criteria: Inclusion Criteria:

* Be a child \> 28 days and \< 5 years old
* Be admitted to Kisantu Hospital
* Have a blood culture sampled upon hospital admission
* Having a caregiver willing and able to provide written informed consent, which will be requested as soon as possible after screening of the other three eligibility criteria. By consenting with study participation of the child, the caregiver agrees to that the child participates in the study procedures at presentation in the hospital, during hospital admission and during 1 month after discharge.

Exclusion Criteria:

* Child died and caregiver left the hospital before enrollment
* Child and caregiver left the hospital before enrollment

Primary outcomes:
measure: Clinical failure (fever)
timeFrame: up to day 7 after start of appropriate antibiotics
measure: Clinical failure (death)
timeFrame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
Secondary outcomes:
measure: In-hospital survival
timeFrame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
measure: Overall survival
timeFrame: One month after discharge (no maximum duration of hospitalization)
measure: Time to fever clearance
timeFrame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
measure: Length of hospital stay
timeFrame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
measure: Microbiological cure
timeFrame: At day 5 of parenteral treatment
measure: Possible disease recurrence
timeFrame: At one month post-discharge (no maximum period of hospitalization)
Other outcomes:
Locations:
city: Kisantu
country: Congo, The Democratic Republic of the
facility: Kisantu Hospital
Study officials:
affiliation: Institute of Tropical Medicine Antwerp
name: Bieke Tack, MD
role: PRINCIPAL_INVESTIGATOR
References: