The burden of multidrug-resistant bacterial infections in low-income countries is alarming. This study aimed to identify the bacterial etiologies and antibiotic resistance patterns among neonates in Jimma, Ethiopia. An observational longitudinal study was conducted among 238 presumptive neonatal sepsis cases tested with blood and/or cerebrospinal fluid culture. The bacterial etiologies were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The antibiotic resistance patterns were determined using the automated disc diffusion method (Bio-Rad) and the results were interpreted based on the European Committee on Antimicrobial Susceptibility Testing 2021 breakpoints. Extended-spectrum β-lactamases were detected using a double disc synergy test and confirmed by Mast discs (Mast Diagnostica GmbH). A total of 152 pathogens were identified. Of these, Staphylococcus aureus (18.4%) was the predominant isolate followed by Klebsiella pneumoniae (15.1%) and Escherichia coli (10.5%). All the isolates exhibited a high rate of resistance to first- and second-line antibiotics ranging from 73.3% for gentamicin to 93.3% for ampicillin. Furthermore, 74.4% of the Gram-negative isolates were extended-spectrum β-lactamase producers and 57.1% of S. aureus strains were methicillin resistant. The case fatality rate was 10.1% and 66.7% of the deaths were attributable to infections by multidrug-resistant pathogens. The study revealed a high rate of infections with multidrug-resistant pathogens. This poses a significant challenge to the current global and national target to reduce neonatal mortality rates. To address these challenges, it is important to employ robust infection prevention practices and continuous antibiotic resistance testing to allow targeted therapy.
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