Determinants of Prolonged Antibiotic Administration in Culture-Negative Evaluations of Early-Onset Neonatal Meningitis: A Retrospective Cohort Study

<b>Background:</b> Early-onset neonatal meningitis (EONM) is a rare but serious condition where antibiotics are often given for extended periods, even without a positive cerebrospinal fluid (CSF) culture. The reasons for this prolonged treatment are unknown. <b>Methodology:</b> This study, conducted at the Women's Wellness and Research Center, Doha, retrospectively analyzed the determinants of prolonged antibiotic therapy among neonates with sterile CSF cultures during the first week of life, born during 2015 to 2018. <b>Results:</b> Of 315 neonates without confirmed meningitis, 96 (30.5%) received prolonged antibiotic therapy. These infants had significantly lower birth weights (2790 g vs. 3170 g) and gestational ages (36.7 weeks vs. 38.5 weeks). They were more likely to require respiratory support, appear ill, and have laboratory abnormalities, including neutropenia, positive blood cultures (36.5% vs. 0.9%), elevated C-reactive protein (CRP), and higher CSF protein. Multivariable analysis identified low Apgar scores (Adjusted Odds Ratio (aOR), 2.82), positive blood cultures (aOR, 118.48), traumatic lumbar puncture (LP) (aOR, 2.14), CRP levels ≥ 50 mg/L (aOR, 2.60), delayed LP (OR, 8.28), and elevated cerebrospinal fluid white cell counts (aOR, 5.47) as independent predictors of prolonged antibiotic use. <b>Conclusions:</b> Prolonged antibiotic use in neonates with sterile CSF cultures and suspected EONS is common and may be driven by certain clinical and laboratory indicators of illness severity and inflammation. Identifying these predictors can support risk-stratified treatment decisions, promoting safer antimicrobial stewardship.