Efficacy of Amikacin and Cefotaxime Synergy Against CTX-M-15-Resistant Klebsiella pneumoniae in Neonatal Sepsis

Abstract

Background:Neonatal sepsis is a significant cause of neonatal mortality, particularly in developing countries, and Klebsiella pneumoniae is a significant contributor to this problem in some Egyptian hospitals. The aim of this study was to investigate the association between CTXM-15 and Klebsiella pneumoniae resistance in neonates.Results:Five hundred and nine positive samples were collected from newborns at some Egyptian hospitals between March 2019 and March 2021, and 101 isolates of Klebsiella pneumoniae were tested for antimicrobial susceptibility using VITEK® 2. The majority of the isolates were from late-onset infections and showed high levels of resistance to several antibiotics, including Ampicillin, Ampicillin/sulbactam, Ceftazidime, and Cefotaxime. The blaCTX-M-15 gene was found to be highly expressed in 66% of the multidrug-resistant Klebsiella pneumoniae isolates, indicating the high level of resistance conferred by this gene. Double combination therapy was evaluated, and the combination of cefotaxime and amikacin showed the most promising results, with synergistic effects against the tested isolates. The addition of magnesium was suggested to enhance cell wall integrity, allowing cefotaxime to diffuse more easily into the cells, and the Cefotaxime- Ethylenediaminetetraacetic acid combined disc and double disc synergy test confirmed the absence of metallo-beta-lactamase CTXM-15.Conclusion:The study highlights the high prevalence of antibiotic resistance in K. pneumoniae isolates in neonatal sepsis in Egypt and demonstrates that the combination of cefotaxime and amikacin may be an effective treatment option for multidrug-resistant isolates with high CTXM-15 expression.