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Updated: Jun 26, 2025

A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low-
Biljana Kakaraskoska Boceska1, Tuba Vilken2, Basil Britto Xavier2,3
1Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. Biljana.KakaraskoskaBoceska@uantwerpen.be.
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.
Insights
New antibiotic combinations show promise for treating neonatal sepsis caused by drug-resistant Gram-negative bacteria (GNB) in low-resource settings. These findings could guide improved treatment strategies for this life-threatening condition.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Neonatal sepsis is a significant cause of mortality in low- and middle-income countries (LMICs).
- Increasing antimicrobial resistance to WHO-recommended treatments compromises effective neonatal sepsis management.
- Gram-negative bacteria (GNB) are primary pathogens, exhibiting high resistance rates to current empiric therapies.
Purpose of the Study:
- To evaluate the in vitro efficacy of novel antibiotic combinations against common GNB causing neonatal sepsis in LMICs.
- To investigate the drug resistance and genetic profiles of prevalent GNB isolates.
- To identify potential alternative treatment regimens for multidrug-resistant (MDR) GNB neonatal sepsis.
Main Methods:
- Analysis of bacterial isolates from the NeoOBS study (NCT03721302), focusing on the five most prevalent GNB species.
- Assessment of antimicrobial resistance patterns, including the prevalence of ESBL and carbapenemase encoding genes.
- In vitro testing of fosfomycin, flomoxef, and amikacin in combination against selected GNB isolates.
Main Results:
- High resistance rates to WHO-recommended antibiotics (ampicillin, gentamicin, cefotaxime) were observed among GNB isolates.
- Prevalence of extended-spectrum beta-lactamase (ESBL) and carbapenemase genes was significant.
- The tested combinations of fosfomycin, flomoxef, and amikacin demonstrated excellent in vitro activity against ESBL-producing Klebsiella pneumoniae and E. coli.
Conclusions:
- Current empiric antibiotic regimens for neonatal sepsis are challenged by widespread GNB drug resistance.
- Novel antibiotic combinations, specifically fosfomycin, flomoxef, and amikacin, show significant in vitro potential.
- Further clinical evaluation of these combinations is warranted for treating neonatal sepsis in high-MDR GNB prevalence areas.
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