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

Salmonella Infection Non-Typhoid Clinical Trial

— TreNTS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04850677
• Other study ID #: ITM202007
• Status: Completed
• Start date: August 1, 2021
• Est. completion date: July 31, 2022

Study information

• Verified date: September 2022
• Source: Institute of Tropical Medicine, Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1884
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Days to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood-stream Infections
• Communicable Diseases
• Infections
• Salmonella Infection Non-Typhoid
• Salmonella Infections
• Sepsis

Intervention

Other:
• Observational Cohort
Observational study

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Kisantu Hospital	Kisantu

Sponsors (5)

Lead Sponsor	Collaborator
Institute of Tropical Medicine, Belgium	Hôpital St. Luc Kisantu, Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo, International Vaccine Institute, KU Leuven

Country where clinical trial is conducted

Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)