Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 17 4 2025 07 29 528 538 Amir Naddaf Maternal-Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mohammad Ansari Nasab Maternal-Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mamak Shariat Maternal-Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Parvaneh Sadeghi-Moghaddam Breastfeeding Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Samaneh Salarvand Department of Anatomical and Clinical Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Zahra Omidi Breastfeeding Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Neda Sadat Kosari Maternal-Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Leyla Sahebi Maternal-Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2024 11 12 2025 07 01 Background and Objectives: Neonatal septicemia is a significant cause of morbidity and mortality in neonatal intensive care units (NICUs). Understanding the patterns of antibiotic resistance and pathogen prevalence is crucial for effective treatment. Materials and Methods: This cross-sectional study was conducted from 2016 to 2022 in the NICU of Vali-Asr Hospital in Tehran. All neonates diagnosed with septicemia were included. Data were collected using the hospital's registry system. Results: A total of 477 infants were hospitalized with sepsis, with 71.7% classified as early-onset sepsis (EOS) and 28.3% as late-onset sepsis (LOS). The most common pathogens were coagulase-negative Staphylococcus (22.1%), Klebsiella pneumoniae (14.9%), and Staphylococcus epidermidis (14.3%). The highest antibiotic resistance was observed for erythromycin (89.8%), clindamycin (80.6%), gentamicin (66.1%), and ciprofloxacin (63.5%), while vancomycin showed the lowest resistance (11.2%). Significant associations were found between antibiotic resistance with low birth weight and chest tube intervention. Trends in antibiotic resistance varied over the study period, with a notable decrease in resistance in 2021. Conclusion: The study highlights the high prevalence of antibiotic resistance in neonatal sepsis, emphasizing the need for continuous monitoring and tailored antibiotic stewardship programs. The findings underscore the importance of individualized treatment approaches to improve outcomes for neonates with sepsis. https://ijm.tums.ac.ir/index.php/ijm/article/view/5131 https://ijm.tums.ac.ir/index.php/ijm/article/download/5131/1795