학술논문
Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
Document Type
article
Author
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
Source
Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024)
Subject
Language
English
ISSN
2041-1723
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.