Yacob Mohammed Yusuf, Adey Feleke Desta, Desta Ayana, Helen Nigussie Aychegrew, Rajiha Abubeker, Biruk Samson, Tolewak Sura, Atsbeha Gebreegziabxier, Abebe Asseffa Negeri, Chala Bashea, Melak Getu, Gebremedhin Gebremichael, Amete Mihret, Eleni Kidane, Ebisa Mezgebu, Sami Sebri, Gemechu Tadesse, Getachew Tollera, Abraham Ali, Gurja Belay Woldemichael
Multidrug-resistant Proteus mirabilis has emerged as an important healthcare-associated pathogen; however, genomic epidemiological data from sub-Saharan Africa remain limited, particularly in military hospital settings. This study aimed to characterize the phenotypic and genomic resistance profiles of P. mirabilis isolates recovered from a military referral hospital in Ethiopia between May 2024 and May 2025. A total of 99 non-duplicate clinical isolates were analyzed using antimicrobial susceptibility testing according to Clinical and Laboratory Standards Institute (CLSI) guidelines, with phenotypic detection of extended-spectrum β-lactamase (ESBL) and carbapenemase production. Whole-genome sequencing was performed on a selected subset of 25 representative ESBL- and/or carbapenemase-associated P. mirabilis isolates to identify resistance genes, determine multilocus sequence types (MLST), analyze plasmid replicons, and reconstruct core-genome phylogeny. Using phenotypic detection, 96.0% of isolates were found to be resistant to at least one third- or fourth-generation cephalosporin, and 99.0% were classified as multidrug-resistant. ESBL production was confirmed in 60.6% (60/99) of isolates, while 6.1% (6/99) demonstrated carbapenemase activity. Genomic analysis revealed diverse ESBL determinants dominated by blaPER-13 (40.0%) and blaVEB-6 (28.0%), with additional detection of blaCTX-M-65. MLST analysis identified nine sequence types, with ST135 predominating (32.0%). Phylogenetic analysis demonstrated moderate genetic heterogeneity, with evidence of multiple lineages circulating within the hospital setting; however, transmission dynamics could not be definitively determined. Plasmid analysis showed a structured replicon distribution dominated by IncQ1 (36.0%) and several Col-type plasmids. These findings demonstrate extensive multidrug resistance associated with diverse ESBL determinants and multiple plasmid replicon types among P. mirabilis isolates in a military healthcare setting. The results highlight the need for strengthened antimicrobial stewardship, improved infection prevention strategies, and integration of genomic surveillance in comparable healthcare environments.