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 carbapenem-resistant Gram-negative pathogens. This study investigates the efficacy of combining low concentrations of colistin with tigecycline against colistin- and carbapenem-resistant 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-resistant strains. All larvae survived when treated with a combination of colistin and tigecycline, 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.

Importance: Colistin resistance in carbapenem-resistant Gram-negative pathogens is a serious challenge in clinical settings. Our study showed that low concentration of colistin can be effective when combined with tigecycline. It presents the possibility of an available treatment option for antibiotic-resistant pathogens.