Comparative analysis of the pathogenicity between multidrug-resistant Acinetobacter baumannii clinical isolates: Isolation of highly pathogenic multidrug-resistant A. baumannii and experimental therapeutics with fourth-generation cephalosporin cefozopran

Abstract

Introduction: The pathogenicity of fatal-outbreak Acinetobacter baumannii isolates has not been fully investigated. This study aimed to compare the pathogenicity between A. baumannii clinical isolates, including multidrug-resistant A. baumannii (MDRA). Materials and methods: Antibiotic susceptibility was determined by the broth microdilution method, and drug-resistant genes were characterized by PCR and sequencing. The pathogenicity of A. baumannii and antibiotic responses were evaluated using the Galleria mellonella infection model. Clinical isolates from an A. baumannii outbreak at our hospital were categorized using the pulse-field gel electrophoresis. Of the 16 isolated A. baumannii clones, 12 clones were resistant to carbapenems (meropenem and imipenem), of which 10 clones were also resistant to amikacin and ciprofloxacin (MDRAs). MDRAs had OXA-51-like β-lactamase gene harboring an insertion sequence in the promoter region and armA gene encoding 16S rRNA methyltransferase. Results: Carbapenem-and/or amikacin-resistant A. baumannii were more pathogenic than carbapenem-and/or amikacin-sensitive A. baumannii in G. mellonella. MDRA isolate TK1033 was more virulent than other A. baumannii isolates. However, TK1033 was sensitive to the fourth-generation cephalosporin cefozopran in addition to minocycline, tigecycline, and polymyxins (colistin and polymyxins B) in vitro and in vivo in the MDRA-G. mellonella infection model. Conclusion: Differences in pathogenicity among carbapenem-resistant A. baumannii clones are consistent with heterogeneous clinical outcomes. Strain TK1033, isolated frequently during the outbreak, was the most virulent, whereas preoutbreak isolate TK1032 was less virulent than other A. baumannii isolates. Infection by high-virulence isolates may be more prevalent during outbreaks. These strains may prove valuable for investigating MDRA virulence and novel therapeutics.