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

Introduction: The pathogenicity of fatal-outbreak isolates has not been fully investigated. This study aimed to compare the pathogenicity between clinical isolates, including multidrug-resistant (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 and antibiotic responses were evaluated using the infection model. Clinical isolates from an outbreak at our hospital were categorized using the pulse-field gel electrophoresis. Of the 16 isolated 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 gene encoding 16S rRNA methyltransferase.

Results: Carbapenem- and/or amikacin-resistant were more pathogenic than carbapenem- and/or amikacin-sensitive in . MDRA isolate TK1033 was more virulent than other 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- infection model.

Conclusion: Differences in pathogenicity among carbapenem-resistant 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 isolates. Infection by high-virulence isolates may be more prevalent during outbreaks. These strains may prove valuable for investigating MDRA virulence and novel therapeutics.