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Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.
- Source :
-
Nature communications [Nat Commun] 2024 May 10; Vol. 15 (1), pp. 3947. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Infant, Newborn
Amikacin pharmacology
Amikacin therapeutic use
Fosfomycin pharmacology
Fosfomycin therapeutic use
beta-Lactamases genetics
beta-Lactamases metabolism
Escherichia coli drug effects
Escherichia coli genetics
Escherichia coli isolation & purification
Developing Countries
Drug Resistance, Multiple, Bacterial genetics
Drug Therapy, Combination
Serratia marcescens drug effects
Serratia marcescens genetics
Serratia marcescens isolation & purification
Enterobacter cloacae drug effects
Enterobacter cloacae genetics
Enterobacter cloacae isolation & purification
Bacterial Proteins genetics
Bacterial Proteins metabolism
Anti-Bacterial Agents therapeutic use
Anti-Bacterial Agents pharmacology
Neonatal Sepsis microbiology
Neonatal Sepsis drug therapy
Gram-Negative Bacteria drug effects
Gram-Negative Bacteria genetics
Gram-Negative Bacteria isolation & purification
Gram-Negative Bacterial Infections drug therapy
Gram-Negative Bacterial Infections microbiology
Acinetobacter baumannii drug effects
Acinetobacter baumannii isolation & purification
Acinetobacter baumannii genetics
Microbial Sensitivity Tests
Klebsiella pneumoniae drug effects
Klebsiella pneumoniae isolation & purification
Klebsiella pneumoniae genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38729951
- Full Text :
- https://doi.org/10.1038/s41467-024-48296-z