Nature Communications (May 2024)
Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
- Biljana Kakaraskoska Boceska,
- Tuba Vilken,
- Basil Britto Xavier,
- Tomislav Kostyanev,
- Qiang Lin,
- Christine Lammens,
- Sally Ellis,
- Seamus O’Brien,
- Renata Maria Augusto da Costa,
- Aislinn Cook,
- Neal Russell,
- Julia Bielicki,
- Amy Riddell,
- Wolfgang Stohr,
- Ann Sarah Walker,
- Eitan Naaman Berezin,
- Emmanuel Roilides,
- Maia De Luca,
- Lorenza Romani,
- Daynia Ballot,
- Angela Dramowski,
- Jeannette Wadula,
- Sorasak Lochindarat,
- Suppawat Boonkasidecha,
- Flavia Namiiro,
- Hoang Thi Bich Ngoc,
- Minh Dien Tran,
- Tim R. Cressey,
- Kanchana Preedisripipat,
- James A. Berkley,
- Robert Musyimi,
- Charalampos Zarras,
- Trusha Nana,
- Andrew Whitelaw,
- Cely Barreto da Silva,
- Prenika Jaglal,
- Willy Ssengooba,
- Samir K. Saha,
- Mohammad Shahidul Islam,
- Marisa Marcia Mussi-Pinhata,
- Cristina Gardonyi Carvalheiro,
- Laura J. V. Piddock,
- Paul T. Heath,
- Surbhi Malhotra-Kumar,
- Michael Sharland,
- Youri Glupczynski,
- Herman Goossens
Affiliations
- Biljana Kakaraskoska Boceska
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Tuba Vilken
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Basil Britto Xavier
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Tomislav Kostyanev
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Qiang Lin
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Christine Lammens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Sally Ellis
- Global Antibiotic Research and Development Partnership (GARDP)
- Seamus O’Brien
- Global Antibiotic Research and Development Partnership (GARDP)
- Renata Maria Augusto da Costa
- Global Antibiotic Research and Development Partnership (GARDP)
- Aislinn Cook
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Neal Russell
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Julia Bielicki
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Amy Riddell
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Wolfgang Stohr
- MRC Clinical Trials Unit, University College London
- Ann Sarah Walker
- MRC Clinical Trials Unit, University College London
- Eitan Naaman Berezin
- Pediatric Infectious Diseases Unit, Santa Casa de Sao Paulo
- Emmanuel Roilides
- Infectious Diseases Unit, 3rd Dept Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University and Hippokration General Hospital
- Maia De Luca
- Infectious Disease Unit, Bambino Gesu Children’s Hospital
- Lorenza Romani
- Infectious Disease Unit, Bambino Gesu Children’s Hospital
- Daynia Ballot
- Department of Pediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand
- Angela Dramowski
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University
- Jeannette Wadula
- Department of Clinical Microbiology & Infectious Diseases, National Health Laboratory Services, CH Baragwanath Academic Hospital, Faculty of Health Sciences, University of Witwatersrand
- Sorasak Lochindarat
- Queen Sirikit National Institute of Child Health
- Suppawat Boonkasidecha
- Queen Sirikit National Institute of Child Health
- Flavia Namiiro
- Mulago Specialized Women’s and Neonatal Hospital
- Hoang Thi Bich Ngoc
- Vietnam National Children’s Hospital
- Minh Dien Tran
- Vietnam National Children’s Hospital
- Tim R. Cressey
- AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences
- Kanchana Preedisripipat
- Chiangrai Prachanukroh Hospital
- James A. Berkley
- Clinical Research Department, KEMRI-Wellcome Trust Research Programme
- Robert Musyimi
- Department of Microbiology, KEMRI-Wellcome Trust Research Programme
- Charalampos Zarras
- Microbiology Department, Hippokration General Hospital
- Trusha Nana
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand
- Andrew Whitelaw
- Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University
- Cely Barreto da Silva
- Infection Control and Prevention Service, Santa Casa de Sao Paulo
- Prenika Jaglal
- Department of Clinical Microbiology & Infectious Diseases, National Health Laboratory Services, CH Baragwanath Academic Hospital, Faculty of Health Sciences, University of Witwatersrand
- Willy Ssengooba
- Makerere University, Department of Medical Microbiology
- Samir K. Saha
- Child Health Research Foundation (CHRF)
- Mohammad Shahidul Islam
- Child Health Research Foundation (CHRF)
- Marisa Marcia Mussi-Pinhata
- Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo
- Cristina Gardonyi Carvalheiro
- Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo
- Laura J. V. Piddock
- Global Antibiotic Research and Development Partnership (GARDP)
- Paul T. Heath
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Surbhi Malhotra-Kumar
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Michael Sharland
- Centre for Neonatal and Pediatric Infection, Institute for Infection & Immunity, St. George’s University of London
- Youri Glupczynski
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- Herman Goossens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp
- DOI
- https://doi.org/10.1038/s41467-024-48296-z
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 12
Abstract
Abstract Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
