Characteristics of Oral Acinetobacter spp. and Evolution of Plasmid-Mediated Carbapenem Resistance in Bacteremia Patients with Hematological Malignancies

Henan Li,* Didaer Talanaite,* Zitong Pan,* Zhiren Wang, Shuyi Wang, Hui Wang Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Henan Li; Hui Wang, Department of Clinical Laboratory, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China, Email [email protected]; [email protected]: Patients with hematological malignancies are more susceptible to infections, leading to a poor prognosis. Acinetobacter colonization is a risk factor for secondary bacteremia.Methods: Antibiotic susceptibility phenotypes and genomic characteristics of 48 oral Acinetobacter spp. and one bloodstream Acinetobacter baumannii from patients with hematological malignancies were analyzed by antimicrobial susceptibility tests and whole-genome sequencing. We conducted comparative genomic analysis of oral and blood isolates from the same patient.Results: A. baumannii was the most common (72.92%, 35/48) Acinetobacter species in oral Acinetobacter spp. isolates. Seventeen different A. baumannii sequence types were identified using the Pasteur MLST scheme; however, the dominant global clones GC1 and GC2 were not present. Among the isolates, 46 (95.8%) were carbapenem-susceptible Acinetobacter spp. One patient treated with meropenem for 15 days developed A. baumannii bacteremia 46 days after the isolation of oral A. baumannii AOR07. Oral and bloodstream isolates from the same patient were closely related to only four non-synonymous mutations on the chromosome. The blaOXA-58 gene was transferred between plasmids through XerCD-mediated recombination, leading to an elevated copy number, causing carbapenem resistance in bloodstream isolates.Conclusion: Oral Acinetobacter spp. may cause secondary bacteremia. The amplification and transfer of blaOXA-58 in the plasmids explained the increased carbapenem resistance in the bloodstream isolate.Keywords: Acinetobacter, within-host evolution, oral colonization, bloodstream infection, hematological malignancies