Phage-antibiotic synergy attenuates Acinetobacter baumannii resistance in refractory pneumonia: a precision therapeutic case

Extensively drug-resistant (XDR) Acinetobacter baumannii pneumonia carries severe pneumonia, respiratory failure and high mortality, showing limited therapeutic options in critically ill patients. Although bacteriophage (phage) therapy represents a promising alternative against drug-resistant infections, its clinical use remains largely empirical. Here, we reported a systematically planned phage-antibiotic combination strategy in a critically ill patient with refractory XDR A. baumannii pneumonia. A virulent phage targeting the patient-derived strain was isolated from hospital wastewater and classified within the class Caudoviricetes , with no virulence, toxin, or antibiotic resistance genes. In vitro time-kill assays showed that phage monotherapy failed to persistently suppress bacteria proliferation, whereas phage-antibiotic therapy achieved synergistic inhibition of A. baumannii growth for over 48 h. The patient received nebulized phage therapy (5 × 10 9 PFU/mL twice daily) combined with intravenous fosfomycin (8 g, every 8 hours), amikacin (0.2 g, every 12 hours), and polymyxin B (500, 000 U, every 12 hours). Clinically, treatment was associated with rapid normalization of arterial carbon dioxide tension (PaCO2), clearance of A. baumannii sputum cultures by day 4, declining inflammatory markers, and no treatment-related toxicity.Longitudinal metagenomic sequencing further revealed approximately 52-fold reduction in pathogen abundance and significant decrease of A. baumannii -associated antimicrobial resistance genes (ARGs) in the lung, highlighting the potential of precision phage-antibiotic therapy for recalcitrant XDR bacterial infections.