Colistin heteroresistance, mechanisms, diagnostic methods, and therapeutic options: A review

The heteroresistance phenotype refers to the presence of bacterial subpopulations with reduced antibiotic susceptibility compared with the main population. Mathematical modelling and computer simulations suggest that heteroresistance can lead to negative treatment outcomes and finally, treatment failure. Due to the low frequency and resistance level of resistant subpopulations, detection of heteroresistance phenotype in the diagnostic laboratory is problematic. Routine laboratory tests do not have the ability to accurately detect heteroresistance, but on the other hand, specific methods are time consuming and expensive. The emergence of colistin heteroresistance is a public health concern that threatens human health. Colistin heteroresistance to date has been reported in eight pathogens including Acinetobacter spp., Klebsiella spp., Enterobacter spp., Pseudomonas spp., Escherichia coli, Salmonella enterica serovar Typhimurium (referred to as Salmonella Typhimurium), Neisseria meningitidis and Stenotrophomonas maltophilia. The growing emergence of colistin heteroresistance worldwide underscores the crucial need for coordinated global action to combat it. Understanding the mechanisms of colistin heteroresistance can help to provide better guidelines for reducing antibiotic resistance and to achieve new therapeutic approaches. Our review showed that the prevalence of colistin heteroresistance strains varies in different countries. It seems that the use of different treatment strategies, especially combination therapy, can be effective in reducing the incidence of resistant subpopulations. Also, the use of new generation diagnostic methods can have a significant impact on treatment. Our findings in this review are needed to raise the awareness of microbiologists and specialists to the colistin heteroresistance mechanisms and to achieve effective treatment.