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

Study Overview
=================
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.

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

Conditions
-----------------
Blood-stream Infections, Salmonella Infection Non-Typhoid

Intervention / Treatment
-----------------
* Other: Observational Cohort


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 28 Days
Maximum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Total<br>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<br>* Observational study<br>|

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) |