PurposeThe rise of carbapenem-resistant A. baumannii (CRAB) is considered a public health problem limiting the treatment options. Our current work studied the emergence and mechanisms of colistin-resistance among CRAB isolates in Egypt.Materials and MethodsSeventeen clinically recovered A. baumannii were identified and screened for their antimicrobial susceptibilities using VITEK-2 system. Colistin susceptibility was evaluated using broth microdilution, and characterization of carbapenem/colistin resistance determinants was performed using whole-genome sequencing (Illumina MiSeq).ResultsAbout 52.9% (9/17) were colistin-resistant. PCR results revealed that all isolates carried blaOXA-51-like genes, blaOXA-23-like was detected in 82.3% (14/17) and blaNDM in 23.5% (4/17). Two isolates harboured blaGES-35 and blaOXA-23. Furthermore, genome analysis of seven isolates revealed six belonged to international clone 2 (IC2) while the remaining isolate was a singleton (ST158), representing a clone circulating in Mediterranean/Middle Eastern countries.ConclusionThe emergence and high incidence of colistin-resistance among CRAB clinical isolates in Egypt are alarming because it further limits therapy options and requires prudent antimicrobial stewardship and stringent infection control measures. Whole-genome sequence analyses suggest that the resistance to colistin was associated with multiple mutations in the pmrCAB genes. The high incidence of the high-risk lineage IC2 harbouring blaOXA-23-like as well as blaNDM is also of concern.