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Background Antimicrobial resistance has become one of the most widespread threats to humans. <i>Acinetobacter baumannii</i> is one of the pathogens responsible for healthcare-associated infections (nosocomial). Colistin is considered the last resort antibiotic against infections with pandrug-resistant (PDR) pathogens. Results: Eleven isolates were detected phenotypically as PDR <i>A. baumannii</i> and were confirmed molecularly using 16S rDNA. The <i>MCR</i>-1 gene was not detected within the chromosomal DNA of the selected isolates. Plasmid bearing the <i>MCR</i>-1 gene was identified in 10 selected isolates of <i>A. baumannii</i> that had not been previously observed to carry the <i>MCR</i>-1 gene. Moreover, the use of colistin in combination with anionic antibiotics or natural compound pterostilbene poses a viable therapeutic alternative for PDR and revives colistin’s bactericidal effects on <i>MCR</i>-1-positive <i>A. baumannii</i>. Finally, the transmission electron microscopy studies proved the synergistic effect of these combinations and revealed the disruption of resistant <i>A. baumannii</i>’s outer membrane and alteration of the permeability properties that allowed overcoming the resistance of the isolates to colistin. Conclusions: Antimicrobial resistance of <i>A. baumannii</i> is related to the presence of the transferable plasmid-bearing <i>MCR</i>-1 gene. This study proved the ability of the combinations of colistin with anionic antibiotics and/or natural compound pterostilbene to restore the bactericidal effect of colistin. Overall, these combinations could be novel promising clinical alternatives against the increasing threat of the widespread multidrug-resistant <i>A. baumannii</i>.