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

doi:10.1038/s41467-024-48296-z

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

^*Corresponding author for this work

Global Antibiotic Research and Development Partnership (GARDP)
St. George's University of London
University College London
Faculdade de Ciências Médicas Santa Casa de São Paulo
IRCCS Ospedale pediatrico Bambino Gesù - Roma
University of the Witwatersrand
Stellenbosch University
Chris Hani Baragwanath Hospital
Thailand Ministry of Public Health
Mulago Specialized Women’s and Neonatal Hospital
Vietnam National Children's Hospital
University of Oxford
Makerere University
Child Health Research Foundation
Universidade de São Paulo
University of Antwerp
Aristotle University of Thessaloniki
Wellcome Trust Research Laboratories Nairobi
Chiangrai Prachanukroh Hospital
Chiang Mai University

Research output: Contribution to journal › Journal article › Research › peer-review

69 Downloads (Orbit)

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.

Original language	English
Article number	3947
Journal	Nature Communications
Volume	15
Issue number	1
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-024-48296-z
Publication status	Published - 2024

Access to Document

10.1038/s41467-024-48296-zLicence: CC BY

FulltextFinal published version, 1.44 MBLicence: CC BY

OpenUrl availability

Check availability in DTU Findit

Cite this

Kakaraskoska Boceska, B., Vilken, T., Xavier, B. B., Kostyanev, T., Lin, Q., Lammens, C., Ellis, S., O’Brien, S., da Costa, R. M. A., Cook, A., Russell, N., Bielicki, J., Riddell, A., Stohr, W., Walker, A. S., Berezin, E. N., Roilides, E., De Luca, M., Romani, L., ... Goossens, H. (2024). Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries. Nature Communications, 15(1), Article 3947. https://doi.org/10.1038/s41467-024-48296-z

@article{8ef748544ae94f2da084cc975b598af4,

title = "Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries",

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.",

author = "\{Kakaraskoska Boceska\}, Biljana and Tuba Vilken and Xavier, \{Basil Britto\} and Tomislav Kostyanev and Qiang Lin and Christine Lammens and Sally Ellis and Seamus O{\textquoteright}Brien and \{da Costa\}, \{Renata Maria Augusto\} and Aislinn Cook and Neal Russell and Julia Bielicki and Amy Riddell and Wolfgang Stohr and Walker, \{Ann Sarah\} and Berezin, \{Eitan Naaman\} and Emmanuel Roilides and \{De Luca\}, Maia and Lorenza Romani and Daynia Ballot and Angela Dramowski and Jeannette Wadula and Sorasak Lochindarat and Suppawat Boonkasidecha and Flavia Namiiro and Ngoc, \{Hoang Thi Bich\} and Tran, \{Minh Dien\} and Cressey, \{Tim R.\} and Kanchana Preedisripipat and Berkley, \{James A.\} and Robert Musyimi and Charalampos Zarras and Trusha Nana and Andrew Whitelaw and \{da Silva\}, \{Cely Barreto\} and Prenika Jaglal and Willy Ssengooba and Saha, \{Samir K.\} and Islam, \{Mohammad Shahidul\} and Mussi-Pinhata, \{Marisa Marcia\} and Carvalheiro, \{Cristina Gardonyi\} and Piddock, \{Laura J.V.\} and Heath, \{Paul T.\} and Surbhi Malhotra-Kumar and Michael Sharland and Youri Glupczynski and Herman Goossens",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41467-024-48296-z",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Kakaraskoska Boceska, B, Vilken, T, Xavier, BB, Kostyanev, T, Lin, Q, Lammens, C, Ellis, S, O’Brien, S, da Costa, RMA, Cook, A, Russell, N, Bielicki, J, Riddell, A, Stohr, W, Walker, AS, Berezin, EN, Roilides, E, De Luca, M, Romani, L, Ballot, D, Dramowski, A, Wadula, J, Lochindarat, S, Boonkasidecha, S, Namiiro, F, Ngoc, HTB, Tran, MD, Cressey, TR, Preedisripipat, K, Berkley, JA, Musyimi, R, Zarras, C, Nana, T, Whitelaw, A, da Silva, CB, Jaglal, P, Ssengooba, W, Saha, SK, Islam, MS, Mussi-Pinhata, MM, Carvalheiro, CG, Piddock, LJV, Heath, PT, Malhotra-Kumar, S, Sharland, M, Glupczynski, Y & Goossens, H 2024, 'Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries', Nature Communications, vol. 15, no. 1, 3947. https://doi.org/10.1038/s41467-024-48296-z

TY - JOUR

T1 - Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

AU - Kakaraskoska Boceska, Biljana

AU - Vilken, Tuba

AU - Xavier, Basil Britto

AU - Kostyanev, Tomislav

AU - Lin, Qiang

AU - Lammens, Christine

AU - Ellis, Sally

AU - O’Brien, Seamus

AU - da Costa, Renata Maria Augusto

AU - Cook, Aislinn

AU - Russell, Neal

AU - Bielicki, Julia

AU - Riddell, Amy

AU - Stohr, Wolfgang

AU - Walker, Ann Sarah

AU - Berezin, Eitan Naaman

AU - Roilides, Emmanuel

AU - De Luca, Maia

AU - Romani, Lorenza

AU - Ballot, Daynia

AU - Dramowski, Angela

AU - Wadula, Jeannette

AU - Lochindarat, Sorasak

AU - Boonkasidecha, Suppawat

AU - Namiiro, Flavia

AU - Ngoc, Hoang Thi Bich

AU - Tran, Minh Dien

AU - Cressey, Tim R.

AU - Preedisripipat, Kanchana

AU - Berkley, James A.

AU - Musyimi, Robert

AU - Zarras, Charalampos

AU - Nana, Trusha

AU - Whitelaw, Andrew

AU - da Silva, Cely Barreto

AU - Jaglal, Prenika

AU - Ssengooba, Willy

AU - Saha, Samir K.

AU - Islam, Mohammad Shahidul

AU - Mussi-Pinhata, Marisa Marcia

AU - Carvalheiro, Cristina Gardonyi

AU - Piddock, Laura J.V.

AU - Heath, Paul T.

AU - Malhotra-Kumar, Surbhi

AU - Sharland, Michael

AU - Glupczynski, Youri

AU - Goossens, Herman

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-024-48296-z

DO - 10.1038/s41467-024-48296-z

M3 - Journal article

C2 - 38729951

AN - SCOPUS:85192829074

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3947

ER -

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Abstract

Access to Document

OpenUrl availability

Fingerprint

Cite this