BackgroundBacterial organisms causing neonatal sepsis have developed increased resistance to commonly used antibiotics. Antimicrobial resistance is a major global health problem. The spread of Multidrug-Resistant Organisms (MDROs) is associated with higher morbidity and mortality rates. This study aimed to determine the risk factors for developing MDRO neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in 2020–2022.MethodsA cross-sectional study was performed on 113 eligible neonates. Patients whose blood cultures were positive for bacterial growth and diagnosed with sepsis were selected as the study sample. Univariate and multivariate analysis with multiple logistic regression were performed to find the associated risk factors for developing multidrug-resistant organism neonatal sepsis. A p-value of < 0.05 was considered significant.ResultsMultidrug-resistant organisms were the predominant aetiology of neonatal sepsis (91/113, 80.5%). The significant risk factors for developing MDRO neonatal sepsis were lower birth weight (OR: 1.607, 95% CI: 1.003 − 2.576, p-value: 0.049), history of premature rupture of the membrane (ProM) ≥ 18 (OR: 3.333, 95% CI: 2.047 − 5.428, p-value < 0.001), meconium-stained amniotic fluid (OR: 2.37, 95% CI: 1.512 − 3.717, p-value < 0.001), longer hospital stays (OR: 5.067, 95% CI: 2.912 − 8.815, p-value < 0.001), lower Apgar scores (OR: 2.25, 95% CI: 1.442 − 3.512, p-value < 0.001), and the use of respiratory support devices, such as invasive ventilation (OR: 2.687, 95% CI: 1.514 − 4.771, p-value < 0.001), and non-invasive ventilation (OR: 2, 95% CI: 1.097 − 3.645, p-value: 0.024).ConclusionsOur study determined various risk factors for multidrug-resistance organism neonatal sepsis and underscored the need to improve infection control practices to reduce the existing burden of drug-resistant sepsis. Low-birth-weight, a maternal history of premature rupture of the membrane lasting more than 18 hours, meconium-stained amniotic fluid, longer hospital stays, a low Apgar score, and the use of ventilators were the risk factors for developing drug-resistant neonatal sepsis.