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Completed

NCT Number: NCT04850677

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

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.

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Key information

Age range

28 day–5 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Kisantu Hospital

Kisantu, Democratic Republic of the Congo

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Observational Cohort

Other

Observational study

Primary outcomes

  1. Clinical failure (fever)

    Time frame: up to day 7 after start of appropriate antibiotics

    Clinical failure (categorical): composite outcome defined as:

    • the persistence of tympanic temperature > 37.5°C after 7 days of appropriate antibiotic treatment
  2. Clinical failure (death)

    Time frame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)

    Clinical failure (categorical): composite outcome defined as:

    • death between the 1st dose of appropriate antibiotics and discharge

Secondary outcomes

  1. In-hospital survival

    Time frame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)

    In-hospital survival (categorical variable): survival measured between 1st dose of appropriate antibiotics and discharge

  2. Overall survival

    Time frame: One month after discharge (no maximum duration of hospitalization)

    Overall survival (time-to-event): survival time measured between 1st dose appropriate antibiotics and one-month post-discharge

  3. Time to fever clearance

    Time frame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)

    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

  4. Length of hospital stay

    Time frame: from 1st dose of antibiotics until discharge. (maximum period of hospitalization is not defined but is usually maximum 4 weeks)

    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

  5. Microbiological cure

    Time frame: At day 5 of parenteral treatment

    Microbiological cure (categorical): no growth of NTS BSI in the follow-up blood culture taken at the day 5 of parenteral antibiotics

  6. Possible disease recurrence

    Time frame: At one month post-discharge (no maximum period of hospitalization)

    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

Sponsors and collaborators

Lead sponsor

Institute of Tropical Medicine, Belgium

Other

Collaborators

  • Hôpital St. Luc Kisantu
  • Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
  • International Vaccine Institute
  • KU Leuven

Registry information

Official study title

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

Acronym: TreNTS

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Apr 20, 2021
Registry last updated
Sep 7, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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