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Analysis from the NeoOBS Global Neonatal Sepsis Prospective Observational Cohort Study Across 19 Hospitals in 11 Countries; Clinical Presentation, Treatment, Mortality Outcomes and Development of the NeoSEP Sepsis Severity Score

40 Pages Posted: 21 Jun 2021

See all articles by Neal Russell

Neal Russell

St. George’s University of London - Paediatric Infectious Diseases Research Group

Wolfgang Stöhr

University College London - Medical Research Council Clinical Trials Unit

Nishad Plakkal

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) - Department of Neonatology

Aislinn Cook

St. George’s University of London - Paediatric Infectious Diseases Research Group

James A. Berkley

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health

Bethou Adhisivam

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) - Department of Neonatology

Ramesh Agarwal

All India Institute of Medical Sciences (AIIMS) - Newborn Division and WHO-CC

Manica Balasegaram

Global Antibiotic Research and Development Partnership (GARDP)

Daynia Ballot

University of the Witwatersrand - School of Clinical Medicine

Adrie Bekker

Stellenbosch University - Department of Paediatrics and Child Health

Eitan Naaman Berezin

Santa Casa de São Paulo - Pediatric Infectious Diseases Unit

Davide Bilardi

Penta Foundation

Suppawat Boonkasidecha

Queen Sirikit National Institute of Child Health

Cristina G. Carvalheiro

University of São Paulo (USP) - Department of Pediatrics

Suman Chaurasia

All India Institute of Medical Sciences (AIIMS) - Department of Paediatrics

Sara Chiurchiu

Bambino Gesù Children's Hospital - Academic Hospital Paediatric Department

Simon Cousens

London School of Hygiene & Tropical Medicine - Department of Infectious Disease Epidemiology

Tim R. Cressey

Chiang Mai University - PHPT/IRD

Trah Minh Dien

Vietnam National Children’s Hospital

Yijun Ding

Capital Medical University - Department of Neonatology

Angela Dramowski

Stellenbosch University - Department of Paediatrics and Child Health

Madhusudhan DS

Seth GS Medical College - Neonatology Department

Ajay Dudeja

Lady Hardinge Medical College - Department of Neonatology

Jinxing Feng

Shenzhen Children's Hospital - Department of Neonatology

Youri Glupczynski

University of Antwerp - Laboratory of Medical Microbiology

Herman Goossens

University of Antwerp - Laboratory of Medical Microbiology

Mohammad Shahidul Islam

Dhaka Shishu Hospital - Child Health Research Foundation (CHRF)

Daniel Jarovsky

Santa Casa de São Paulo - Pediatric Infectious Diseases Unit

Nathalie Khavessian

Global Antibiotic Research and Development Partnership (GARDP)

Meera Khorona

Queen Sirikit National Institute of Child Health - Neonatal Unit

Tomislav Kostyanev

University of Antwerp - Laboratory of Medical Microbiology

Matthias Larsson

Karolinska Institutet - Department of Global Public Health

Maia De Luca

Bambino Gesù Children's Hospital - Academic Hospital Paediatric Department

Surbhi Malhotra-Kumar

University of Antwerp - Laboratory of Medical Microbiology

Marisa M. Mussi-Pinhata

University of São Paulo (USP) - Department of Pediatrics

Ruchi Nanavati

Seth GS Medical College - Neonatology Department

Sushma Nangia

Lady Hardinge Medical College - Department of Neonatology; Kalawati Saran Children's Hospital

Jolly Nankunda

Makerere University - Johns Hopkins University Research Collaboration

Borna Nyaoke

Global Antibiotic Research and Development Partnership (GARDP)

Christina W. Obiero

Kemri-Wellcome Trust Research Programme - Clinical Research Department,

Maxensia Owor

Makerere University - Johns Hopkins University Research Collaboration

Wang Ping

Capital Medical University - Beijing Obstetrics and Gynecology Hospital

Kanchana Preedisripipat

Chiangrai Prachanukroh Hospital

Shamim Qazi

World Health Organization (WHO) - Department of Maternal, Newborn, Child and Adolescent Health

Tanusha Ramdin

University of the Witwatersrand - School of Clinical Medicine

Amy Riddell

St. George’s University of London - Paediatric Infectious Diseases Research Group

Emmanuel Roilides

Aristotle University and Hippokration General Hospital - Infectious Diseases Unit

Samir Saha

Dhaka Shishu Hospital - Child Health Research Foundation (CHRF)

Kosmas Sarafidis

Aristotle University and Hippokration General Hospital - Infectious Diseases Unit

Reenu Thomas

University of the Witwatersrand - School of Clinical Medicine

Sithembiso Christopher Velaphi

University of the Witwatersrand - School of Clinical Medicine

Tuba Vilken

University of Antwerp - Laboratory of Medical Microbiology

Yajuan Wang

Capital Institute of Pediatrics - Department of Neonatology

Yonghong Yang

Shenzhen Children's Hospital - Department of Neonatology

Liu Zunjie

Capital Medical University - Beijing Obstetrics and Gynecology Hospital

Sally Ellis

Global Antibiotic Research and Development Partnership (GARDP)

Julia Bielicki

St. George’s University of London - Paediatric Infectious Diseases Research Group

Sarah Walker

University College London - Medical Research Council Clinical Trials Unit

Paul T. Heath

University of London - Institute of Infection and Immunity

Mike Sharland

St. George’s University of London - Paediatric Infectious Diseases Research Group

More...

Abstract

Background: Neonatal sepsis is associated with high mortality, but there is limited clinical data on outcomes in hospital facilities in low and middle income countries (LMIC). The NeoOBS study aimed to determine the clinical features, pathogens and clinical outcomes of infants presenting with neonatal sepsis in hospitals globally.

Methods: Infants <60 days of age, fulfilling at least 2 sepsis criteria were enrolled across 19 sites in 11 countries, with prospective data collection to 28 days. A multivariable Cox regression model was built to predict mortality and develop a sepsis severity score in 85% of infants (randomly selected) and validated in 15%.

Findings: 3204 infants were enrolled between 2018-2020; median (IQR) postnatal age was 5 (2-15) days, birth weight 2500g (1400-3000g), with 4 (2-5) clinical and 1 (0-2) laboratory sepsis criteria, and 69% hospitalised since birth. Overall mortality was 11.3% (95%CI 10.2-12.5%; n=350), but higher in infants with culture positive blood stream infection at baseline (17.7%, 95%CI 14.7-21.1%, n=564) than culture negative (n=2631, 9.9%, 95%CI 8.8-11.2%). Among 309 infection-related deaths, 59% (n=183) occurred in healthcare-associated infections (HAI). Klebsiella pneumoniae was the most common pathogen identified (n=132, 23.4% of baseline cultures). A wide variety of antibiotic regimens were prescribed, with frequent use of carbapenems. A sepsis severity score was developed using infants’ characteristics, supportive care, and clinical signs. In the validation sample, mortality (95%CI) was 1% (0-5%), 6% (4-10%), and 28% (19-39%) in low (score 0-3), medium (4-6) and high (7-14) risk groups, respectively.

Interpretation: High rates of HAI, mortality and carbapenem use were observed in neonatal units globally. Novel strategic treatment and prevention trials are urgently required, where the NeoSEP score may have utility.

Funding Information: The study was sponsored by the Global Antibiotic Research and Development Partnership (GARDP) with additional funding from: Bill and Melinda Gates Foundation, German Federal Ministry of Education and Research (BMBF), South African Medical Research Council, UK Department of Health and Social Care, Monaco and in-kind contribution from Indian Council for Medical Research.

Declaration of Interests: None to declare.

Ethics Approval Statement: Ethical approval was obtained both from St. George’s, University of London Research Ethics Committee and sites’ local, central or national ethics committees and other relevant local bodies, where required.

Suggested Citation

Russell, Neal and Stöhr, Wolfgang and Plakkal, Nishad and Cook, Aislinn and Berkley, James A. and Adhisivam, Bethou and Agarwal, Ramesh and Balasegaram, Manica and Ballot, Daynia and Bekker, Adrie and Berezin, Eitan Naaman and Bilardi, Davide and Boonkasidecha, Suppawat and Carvalheiro, Cristina G. and Chaurasia, Suman and Chiurchiu, Sara and Cousens, Simon and Cressey, Tim R. and Dien, Trah Minh and Ding, Yijun and Dramowski, Angela and DS, Madhusudhan and Dudeja, Ajay and Feng, Jinxing and Glupczynski, Youri and Goossens, Herman and Islam, Mohammad Shahidul and Jarovsky, Daniel and Khavessian, Nathalie and Khorona, Meera and Kostyanev, Tomislav and Larsson, Matthias and Luca, Maia De and Malhotra-Kumar, Surbhi and Mussi-Pinhata, Marisa M. and Nanavati, Ruchi and Nangia, Sushma and Nankunda, Jolly and Nyaoke, Borna and Obiero, Christina W. and Owor, Maxensia and Ping, Wang and Preedisripipat, Kanchana and Qazi, Shamim and Ramdin, Tanusha and Riddell, Amy and Roilides, Emmanuel and Saha, Samir and Sarafidis, Kosmas and Thomas, Reenu and Velaphi, Sithembiso Christopher and Vilken, Tuba and Wang, Yajuan and Yang, Yonghong and Zunjie, Liu and Ellis, Sally and Bielicki, Julia and Walker, Sarah and Heath, Paul T. and Sharland, Mike, Analysis from the NeoOBS Global Neonatal Sepsis Prospective Observational Cohort Study Across 19 Hospitals in 11 Countries; Clinical Presentation, Treatment, Mortality Outcomes and Development of the NeoSEP Sepsis Severity Score. Available at SSRN: https://ssrn.com/abstract=3864901 or http://dx.doi.org/10.2139/ssrn.3864901

Neal Russell (Contact Author)

St. George’s University of London - Paediatric Infectious Diseases Research Group ( email )

London
United Kingdom

Wolfgang Stöhr

University College London - Medical Research Council Clinical Trials Unit

Gower Street
London, WC1E 6BT
United Kingdom

Nishad Plakkal

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) - Department of Neonatology ( email )

Puducherry
India

Aislinn Cook

St. George’s University of London - Paediatric Infectious Diseases Research Group ( email )

London
United Kingdom

James A. Berkley

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

Bethou Adhisivam

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) - Department of Neonatology ( email )

Puducherry
India

Ramesh Agarwal

All India Institute of Medical Sciences (AIIMS) - Newborn Division and WHO-CC

Aurobindo Marg
Ansari Nagar East
New Delhi, New Delhi 110029
India

Manica Balasegaram

Global Antibiotic Research and Development Partnership (GARDP) ( email )

Geneva
Switzerland

Daynia Ballot

University of the Witwatersrand - School of Clinical Medicine

1 Jan Smuts Avenue
Johannesburg, GA Gauteng 2000
South Africa

Adrie Bekker

Stellenbosch University - Department of Paediatrics and Child Health

Eitan Naaman Berezin

Santa Casa de São Paulo - Pediatric Infectious Diseases Unit

São Paulo
Brazil

Davide Bilardi

Penta Foundation

Padova
Italy

Suppawat Boonkasidecha

Queen Sirikit National Institute of Child Health

Bangkok
Thailand

Cristina G. Carvalheiro

University of São Paulo (USP) - Department of Pediatrics ( email )

Av. Prof. Luciano Gualberto 380
Sao Paulo, 05508-010
Brazil

Suman Chaurasia

All India Institute of Medical Sciences (AIIMS) - Department of Paediatrics ( email )

Aurobindo Marg
Ansari Nagar East
New Delhi, New Delhi 110029
India

Sara Chiurchiu

Bambino Gesù Children's Hospital - Academic Hospital Paediatric Department ( email )

Rome
Italy

Simon Cousens

London School of Hygiene & Tropical Medicine - Department of Infectious Disease Epidemiology ( email )

Keppel Street
London, WC1E 7HT
United Kingdom

Tim R. Cressey

Chiang Mai University - PHPT/IRD ( email )

Huay Kaew Road
Chiang Mai, Chiang Mai 50100
Thailand

Trah Minh Dien

Vietnam National Children’s Hospital ( email )

Hanoi
Vietnam

Yijun Ding

Capital Medical University - Department of Neonatology ( email )

Beijing
China

Angela Dramowski

Stellenbosch University - Department of Paediatrics and Child Health ( email )

Private Bag X1
Stellenbosch, Western Cape 7602
South Africa

Madhusudhan DS

Seth GS Medical College - Neonatology Department ( email )

Mumbai
India

Ajay Dudeja

Lady Hardinge Medical College - Department of Neonatology ( email )

New Delhi
India

Jinxing Feng

Shenzhen Children's Hospital - Department of Neonatology ( email )

Mintian Rd, FuTian CBD
Futian Qu
Shenzhen Shi, Guangdong Sheng 518026
China

Youri Glupczynski

University of Antwerp - Laboratory of Medical Microbiology ( email )

Prinsstraat 13
Antwerp, 2000
Belgium

Herman Goossens

University of Antwerp - Laboratory of Medical Microbiology ( email )

Belgium

Mohammad Shahidul Islam

Dhaka Shishu Hospital - Child Health Research Foundation (CHRF)

Sher-e-Bangla Nagar
Dhaka, 1207
Bangladesh

Daniel Jarovsky

Santa Casa de São Paulo - Pediatric Infectious Diseases Unit ( email )

São Paulo
Brazil

Nathalie Khavessian

Global Antibiotic Research and Development Partnership (GARDP) ( email )

Geneva
Switzerland

Meera Khorona

Queen Sirikit National Institute of Child Health - Neonatal Unit ( email )

Bangkok
Thailand

Tomislav Kostyanev

University of Antwerp - Laboratory of Medical Microbiology ( email )

Prinsstraat 13
Antwerp, 2000
Belgium

Matthias Larsson

Karolinska Institutet - Department of Global Public Health ( email )

Granits väg 4
Section for Integrative Physiology
Solna, Stockholm 17171
Sweden

Maia De Luca

Bambino Gesù Children's Hospital - Academic Hospital Paediatric Department ( email )

Rome
Italy

Surbhi Malhotra-Kumar

University of Antwerp - Laboratory of Medical Microbiology ( email )

Belgium

Marisa M. Mussi-Pinhata

University of São Paulo (USP) - Department of Pediatrics ( email )

Av. Prof. Luciano Gualberto 380
Sao Paulo, 05508-010
Brazil

Ruchi Nanavati

Seth GS Medical College - Neonatology Department ( email )

Mumbai
India

Sushma Nangia

Lady Hardinge Medical College - Department of Neonatology ( email )

New Delhi
India

Kalawati Saran Children's Hospital

New Delhi
India

Jolly Nankunda

Makerere University - Johns Hopkins University Research Collaboration ( email )

P.O Box 7062
Kampala, CENTRAL 256
Uganda

Borna Nyaoke

Global Antibiotic Research and Development Partnership (GARDP) ( email )

Geneva
Switzerland

Christina W. Obiero

Kemri-Wellcome Trust Research Programme - Clinical Research Department, ( email )

Kilifi
Kenya

Maxensia Owor

Makerere University - Johns Hopkins University Research Collaboration ( email )

P.O Box 7062
Kampala, CENTRAL 256
Uganda

Wang Ping

Capital Medical University - Beijing Obstetrics and Gynecology Hospital

Beijing
China

Kanchana Preedisripipat

Chiangrai Prachanukroh Hospital ( email )

Chiang Rai
Thailand

Shamim Qazi

World Health Organization (WHO) - Department of Maternal, Newborn, Child and Adolescent Health

Avenue Appia 20
Geneva, 1211
Switzerland

Tanusha Ramdin

University of the Witwatersrand - School of Clinical Medicine ( email )

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Amy Riddell

St. George’s University of London - Paediatric Infectious Diseases Research Group ( email )

London
United Kingdom

Emmanuel Roilides

Aristotle University and Hippokration General Hospital - Infectious Diseases Unit ( email )

Thessaloniki
Greece

Samir Saha

Dhaka Shishu Hospital - Child Health Research Foundation (CHRF) ( email )

Sher-e-Bangla Nagar
Dhaka, 1207
Bangladesh

Kosmas Sarafidis

Aristotle University and Hippokration General Hospital - Infectious Diseases Unit ( email )

Thessaloniki
Greece

Reenu Thomas

University of the Witwatersrand - School of Clinical Medicine ( email )

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Sithembiso Christopher Velaphi

University of the Witwatersrand - School of Clinical Medicine ( email )

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Tuba Vilken

University of Antwerp - Laboratory of Medical Microbiology ( email )

Prinsstraat 13
Antwerp, 2000
Belgium

Yajuan Wang

Capital Institute of Pediatrics - Department of Neonatology

Beijing
China

Yonghong Yang

Shenzhen Children's Hospital - Department of Neonatology

Mintian Rd, FuTian CBD
Futian Qu
Shenzhen Shi, Guangdong Sheng 518026
China

Liu Zunjie

Capital Medical University - Beijing Obstetrics and Gynecology Hospital ( email )

Beijing
China

Sally Ellis

Global Antibiotic Research and Development Partnership (GARDP)

Geneva
Switzerland

Julia Bielicki

St. George’s University of London - Paediatric Infectious Diseases Research Group

London
United Kingdom

Sarah Walker

University College London - Medical Research Council Clinical Trials Unit

Gower Street
London, WC1E 6BT
United Kingdom

Paul T. Heath

University of London - Institute of Infection and Immunity ( email )

London
United Kingdom

Mike Sharland

St. George’s University of London - Paediatric Infectious Diseases Research Group ( email )

Cranmer Terrace
Tooting, SW17 0RE
United Kingdom

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