The clinical features, antimicrobial susceptibility patterns and genomics of bacteria causing neonatal sepsis in a children’s hospital in Vietnam

ISRCTN	ISRCTN69124914
DOI	https://doi.org/10.1186/ISRCTN69124914
Protocol serial number	19EN
Sponsor	Oxford University Clinical Research Unit
Funder	Wellcome Trust

Submission date: 11/05/2017
Registration date: 06/06/2017
Last edited: 06/02/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Neonatal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Neonatal sepsis is a blood infection that occurs in babies younger than 90 days old. Antibiotics are used to treat bacterial infections but some bacteria have become resistant to antibiotics. In Vietnam little is known about the clinical features of neonatal sepsis, antibiotic susceptibility and resistance, and how these impact on disease and outcome. To address this, the aim of this study is to assess the clinical characteristics of babies with sepsis and to investigate the bacteria causing sepsis, including their resistance to antibiotics.

Who can participate?
Babies aged under 1 month with sepsis

What does the study involve?
The clinical characteristics of babies with sepsis are recorded and blood samples are taken to study the bacteria causing sepsis and their susceptibility to antibiotics. The impact of specific bacteria and antibiotic resistance on patient outcomes (mortality, length of stay and cost of treatment) is assessed.

What are the possible benefits and risks of participating?
The results of this study could be used to improve the treatment of bloodstream infections and run further studies focused on preventing sepsis. This is a minimal risk study because it does not involve any new drugs or treatments. The collection of all blood samples for use in this study is performed as part of routine clinical assessments and is consistent with the local standard of care and good clinical practice.

Where is the study run from?
Children’s Hospital 1 and the Oxford University Clinical Research Unit (OUCRU-VN) (Vietnam)

When is the study starting and how long is it expected to run for?
August 2016 to December 2020

Who is funding the study?
Wellcome Trust (UK)

Who is the main contact?
Dr Toan Nguyen

Contact information

Dr Toan Nguyen
Scientific

84 De Tham Street
Cau Ong Lanh Ward
District 1
Ho Chi Minh
700000
Viet Nam

ORCID ID	0000-0003-0904-9807

Study information

Primary study design	Observational
Study design	Observational prospective study
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	The clinical features, antimicrobial susceptibility patterns and genomics of bacteria causing neonatal sepsis in a children’s hospital in Vietnam: an observational prospective study
Study objectives	There are limited contemporary data on the causes of bacterial sepsis in neonates in Vietnam. The trialists hypothesize that there has been a dramatic surge in multi-drug resistant Gram-negative organisms and the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The aim is to investigate the clinical features, major causes of neonatal sepsis, distribution of pathogens, their antimicrobial susceptibility patterns and the genomics of bacteria as well as their association with disease outcome. The trialists hope that by studying and defining aetiology, antimicrobial susceptibility patterns and disease outcome they will be able to develop an improved approach to managing neonatal sepsis and will use these data to initiate intervention studies focused on preventing bloodstream infections with antimicrobial resistant pathogens in neonates with sepsis.
Ethics approval(s)	Oxford Tropical Research Ethics Committee (OxTREC), 04/08/2016, ref: 35-16
Health condition(s) or problem(s) studied	Neonatal sepsis
Intervention	An observational prospective study to characterize the clinical features of neonates with sepsis, the microbial population structure, antimicrobial susceptibility patterns and the antimicrobial resistance genes of the bacteria causing that sepsis. Routinely, the investigators record on the paper case report form the data including demographic, clinical and laboratory information of the patients, the date of blood draw, the number of blood culture bottles inoculated, the result of the culture (whether positive or negative) and the susceptibility of the isolate to commonly used antimicrobial agents. Data from these records are subsequently entered into CliRes Data Management System of Oxford University Clinical Research Unit. These will be source data for this study. The number of patients admitted to the hospital annually will be obtained from hospital records. As part of this study all isolates from blood are stored and archived at -800C. These isolates will be re-cultured and the identification will be re-confirmed. Selected isolated organisms from blood will have further molecular characterization at a later date.
Intervention type	Other
Primary outcome measure(s)	1. Clinical characteristics of neonates with sepsis, recorded on a case report form during hospital stay from admission to discharge 2. The etiology of neonatal sepsis and the distribution of pathogens by clinical departments, assessed using the blood culture results including the isolation and identification information recorded on a case report form during hospital stay from admission to discharge 3. Antimicrobial susceptibility and resistance of isolated bacteria, assessed using disc testing, minimum inhibitory concentrations, conventional PCR and genome sequencing of resistance genes, during hospital stay from admission to discharge 4. The impact of specific bacteria and antimicrobial resistance profile on patient outcomes (mortality, length of stay and cost of treatment), recorded on a case report form during hospital stay at day 7, day 14, day 21 and day 28 after admission and at discharge 5. Genome sequence profile of isolated bacteria, assessed using Illumina whole genome sequencing at the end of recruitment
Key secondary outcome measure(s)	1. Antimicrobial resistance profile and gene distribution of the isolated bacteria by clinical departments, assessed using disc testing, minimum inhibitory concentrations, conventional PCR and genome sequencing of resistance genes, at the end of recruitment 2. The population structure of the isolated bacteria, the antimicrobial resistance gene pool and other horizontally transferred DNA, assessed by genome sequencing at the end of recruitment
Completion date	31/12/2020

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	All
Target sample size at registration	800
Key inclusion criteria	1. Neonates (≤1 month of age) 2. Diagnosis of probable sepsis or confirmed sepsis 3. Have blood culture taken 4. Inpatient at local hospital between 2017 and 2018 5. Informed consent given by parents or guardians
Key exclusion criteria	Informed consent not given
Date of first enrolment	02/01/2017
Date of final enrolment	31/12/2019

Locations

Countries of recruitment

Viet Nam

Study participating centre

Oxford University Clinical Research Unit

700000
Viet Nam

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	02/09/2022	06/02/2023	Yes	No
Protocol article	protocol	24/01/2018		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

06/02/2023: Publication reference added.
14/02/2018: Publication reference added.