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.

PubMed

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.