Effect of colistin-tigecycline combination on colistin-resistant and carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii

There is a critical need for treatment strategies to combat carbapenemresistant Gram-negative pathogens. This study investigates the efficacy of combining low concentrations of colistin with tigecycline against colistin- and carbapenem-resist ant Klebsiella pneumoniae and Acinetobacter baumannii strains. We used two strains of KPC-2-producing K. pneumoniae and OXA-23-producing A. baumannii, both of which are highly colistin-resistant. In the in vitro time-killing assays, monotherapy with colistin (2 mg/L) and tigecycline (4 or 8 mg/L) was ineffective against all strains. However, the combination of colistin (2 mg/L) and tigecycline (4 or 8 mg/L) inhibited bacterial growth. Survival analysis of Galleria mellonella larvae also demonstrated the efficacy of low concentrations of colistin and tigecycline against colistin- and carbapenem-resist ant strains. All larvae survived when treated with a combination of colistin and tigecy cline, whereas monotherapy with either colistin or tigecycline did not increase larval survival rates. This study proposes using a combination of tigecycline and colistin at clinical concentrations to treat carbapenem-resistant K. pneumoniae and A. baumannii, regardless of colistin resistance.