Treating Non-typhoidal Salmonella Bloodstream Infections in Children Under Five in DR Congo: a Cohort Study (TreNTS)

Treating Non-typhoidal Salmonella Bloodstream Infections in Children Under Five in DR Congo: a Cohort Study - TreNTS

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.

Study Overview

• Status: Completed
• Conditions: Blood-stream Infections; Salmonella Infection Non-Typhoid
• Intervention / Treatment: Other: Observational Cohort

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.

• Study Type: Observational
• Enrollment (Actual): 1884

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Kisantu, Congo, The Democratic Republic of the
    • Kisantu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Total; All subjects in the study belong to the same group/cohort. As this is an observational study there is no intervention planned.	Other: Observational Cohort; Observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical failure (fever)	Clinical failure (categorical): composite outcome defined as: - the persistence of tympanic temperature > 37.5°C after 7 days of appropriate antibiotic treatment	up to day 7 after start of appropriate antibiotics
Clinical failure (death)	Clinical failure (categorical): composite outcome defined as: - death between the 1st dose of appropriate antibiotics and discharge	from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital survival	In-hospital survival (categorical variable): survival measured between 1st dose of appropriate antibiotics and discharge	from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
Overall survival	Overall survival (time-to-event): survival time measured between 1st dose appropriate antibiotics and one-month post-discharge	One month after discharge (no maximum duration of hospitalization)
Time to fever clearance	Time to fever clearance (time-to-event): fever clearance is defined as a tympanic temperature ≤37.5°C for at least 2 days [15-17], measured between 1st dose appropriate antibiotics and discharge	from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
Length of hospital stay	Length of hospital stay (time-to-event): number of days that the child was admitted to the hospital, measured between moment of admission and discharge	from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)
Microbiological cure	Microbiological cure (categorical): no growth of NTS BSI in the follow-up blood culture taken at the day 5 of parenteral antibiotics	At day 5 of parenteral treatment
Possible disease recurrence	Possible disease recurrence: Fever recurrence: reappearance of objective (measured temperature > 37.5°C) or subjective fever according to the caregiver, measured between moment of fever clearance and one-month post-discharge; All-cause hospital readmission: readmission at a hospital or health center irrespective of the cause of readmission, measured between discharge and one-month post-discharge; All-cause care seeking at health care facilities: consultation of any health care facility (traditional, private or official) irrespective of the reason for consultation, measured between discharge and one-month post-discharge; Re-initiation of antibiotics or antimalarials: start of antibiotic or antimalarial treatment after stop of antibiotic treatment for NTS BSI irrespective of the reason for treatment, measured between last dose of appropriate antibiotics and one-month post-discharge	At one month post-discharge (no maximum period of hospitalization)

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: KU Leuven; Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo; International Vaccine Institute; Hôpital St. Luc Kisantu
• Investigators: Principal Investigator: Bieke Tack, MD, Institute Of Tropical Medicine Antwerp

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: April 7, 2021
• First Submitted That Met QC Criteria: April 15, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Sepsis; Infections; Communicable Diseases; Salmonella Infections
• Other Study ID Numbers: ITM202007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The data sharing procedure for the study will comply with the Institute of Tropical Medicine's data sharing policy on open access to research data. After publishing the manuscript, participant level study data may be shared with other interested users under restricted conditions or made available through an open data repository. These study data will only be shared if the enrolled child are anonymized so that their identity cannot be determined, neither directly nor indirectly. Any subsequent sharing of participant level data will require approval from Institut National de Recherche Biomédicale (INRB) and Institute of Tropical Medicine (ITM).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No