Phage-antibiotic synergy against Acinetobacter baumannii: a scoping review

Acinetobacter baumannii is a critical priority pathogen within the ESKAPE group, exhibiting extensive drug resistance. Phage-antibiotic interactions, including synergistic effects, re-sensitization, and antibiofilm activity, have emerged as promising strategies to enhance antibacterial activity and potentially restore antibiotic susceptibility. This scoping review aimed to map and synthesize the current knowledge on phage-antibiotic interactions against drug-resistant A. baumannii . A scoping review was conducted following the Arksey and O’Malley framework and PRISMA-ScR guidelines. PubMed, Scopus, and EMBASE were searched for research articles published between January 01, 2000 and July 23, 2026. Eligible studies were those evaluating bacteriophages combined with antibiotics against A. baumannii and reporting interaction outcomes. Data were extracted on study characteristics, experimental models, antibiotics tested, interaction metrics and outcomes, mechanisms associated with reported synergy, and reported limitations. Due to methodological heterogeneity, findings were synthesized using a descriptive narrative approach. Thirty-nine studies met the inclusion criteria, encompassing in vitro, ex vivo, and in vivo models. Synergistic interactions were most commonly reported with carbapenems, polymyxins, and cephalosporins, the three most extensively tested antibiotic classes. Fluoroquinolones, tetracyclines/glycylcyclines, and penicillin/β-lactamase-inhibitor combinations also predominantly showed synergy, whereas aminoglycosides displayed the most heterogeneous outcomes, including synergy, antagonism, indifference, and mixed strain-specific results depending on the specific phage–antibiotic pair. Phage-antibiotic combinations generally outperformed monotherapy in reducing bacterial burden, disrupting biofilms, and improving survival in in vivo models. Preclinical in vivo or ex vivo validation was reported in 19 of 39 studies, with these studies showing markedly enhanced survival and bacterial clearance with phage–antibiotic combinations relative to phage or antibiotic monotherapy. Phage-antibiotic interactions represent a promising investigational strategy against MDR/XDR A. baumannii . However, significant variability in experimental designs and interaction assessment methods currently limits clinical translation. Future studies should focus on standardizing interaction and synergy assessment methods, systematically screening phage–antibiotic combinations, elucidating the molecular mechanisms underlying these interactions, and conducting robust pharmacokinetic and pharmacodynamic studies to support the development of clinically applicable therapies.