From the Guidelines
Efflux pumps are not considered the main cause of colistin resistance in bacterial isolates. The primary mechanism of colistin resistance is typically modification of the bacterial lipopolysaccharide (LPS) structure, particularly through alterations in the lipid A component. This occurs most commonly via chromosomal mutations in the PmrA/PmrB and PhoP/PhoQ two-component regulatory systems, or through the acquisition of mobile colistin resistance (mcr) genes, as seen in studies such as 1. These modifications reduce the net negative charge of the bacterial outer membrane, decreasing the binding affinity of the positively charged colistin molecules. While efflux pumps can contribute to resistance against many antimicrobials by actively expelling them from bacterial cells, they play a relatively minor role in colistin resistance compared to LPS modifications, as discussed in the context of other antimicrobial resistances 1. This understanding is important for developing effective strategies to combat colistin resistance, as targeting LPS modification pathways rather than efflux pump inhibition would likely be more successful in restoring colistin susceptibility in resistant isolates. Some key points to consider in the context of colistin resistance include:
- The role of heteroresistance, as described in studies like 1, which may impact the development of resistance and treatment outcomes.
- The potential for colistin resistance to emerge through various mechanisms, highlighting the need for careful management and monitoring of colistin use.
- The importance of understanding the specific mechanisms of resistance in different bacterial isolates to inform effective treatment strategies.
From the Research
Efflux Pumps and Colistin Resistance
- Efflux pumps are a mechanism associated with resistance to antimicrobial agents in bacteria 2, 3.
- Studies have shown that efflux pump inhibitors (EPIs) can reverse colistin resistance in Gram-negative bacteria, suggesting that efflux pumps play a role in colistin resistance 2, 3, 4.
- The use of EPIs, such as CCCP, has been shown to decrease the minimum inhibitory concentration (MIC) of colistin in bacteria with known and unknown colistin resistance mechanisms 2.
- The combination of colistin with EPIs and other inhibitors, such as MarR inhibitors, has been shown to be effective in restoring colistin sensitivity in colistin-resistant bacteria 4.
Prevalence of Colistin Resistance
- Colistin resistance is a growing concern worldwide, particularly in countries where colistin is widely used 5.
- The prevalence of colistin resistance varies by region, with higher rates reported in the Mediterranean and South-East Asia 5.
- The emergence of colistin resistance is often associated with the overuse and misuse of antibiotics, highlighting the need for effective infection prevention and control measures and strict use of antibiotics 5.
Mechanisms of Colistin Resistance
- Colistin resistance can occur through various mechanisms, including the modification of lipopolysaccharides, the production of efflux pumps, and the presence of resistance genes such as mcr-1 3, 5.
- The role of efflux pumps in colistin resistance is complex and may involve the regulation of gene expression and the interaction with other resistance mechanisms 3.
- Further research is needed to fully understand the mechanisms of colistin resistance and to develop effective strategies for preventing and treating colistin-resistant infections 2, 3, 4.