Background <p>Elizabethkingia anophelis is an emerging multidrug-resistant pathogen associated with severe neonatal infections and high mortality. Due to its intrinsic resistance to multiple antibiotics, including β-lactams, optimal antimicrobial therapy remains challenging. We report a rare case of neonatal meningitis complicated by brain abscess caused by piperacillin-tazobactam–resistant Elizabethkingia anophelis.</p> Case presentation <p>A full-term neonate presented with fever and poor responsiveness on day 15 after birth. Initial empirical antibiotic therapy was ineffective. Blood culture confirmed Elizabethkingia anophelis with resistance to piperacillin-tazobactam. Based on antimicrobial susceptibility testing, the treatment regimen was adjusted to levofloxacin combined with vancomycin. The patient showed marked clinical improvement, with normalization of temperature, negative blood cultures, and gradual resolution of the brain abscess. No significant adverse effects were observed during treatment.</p> Conclusion <p>This case highlights the challenge of individualized antimicrobial selection in piperacillin-tazobactam-resistant neonatal Elizabethkingia meningitis. Early pathogen identification and timely optimization of antimicrobial therapy, including the judicious use of fluoroquinolones, may be critical for improving clinical outcomes.</p>