Colistin Resistance: A Simple Test to Combat a Growing Threat
"New phenotypic method offers rapid screening for MCR-1 mediated resistance, crucial for combating antibiotic resistance."
The rise of antibiotic-resistant bacteria poses a significant threat to global health. Polymyxins, including colistin, are often the last line of defense against multidrug-resistant Gram-negative pathogens. However, resistance to these antibiotics is increasing, driven in part by the spread of mobilized colistin resistance (mcr) genes.
A particularly concerning mechanism of resistance is mediated by the mcr-1 gene, which can transfer easily between bacteria, leading to rapid dissemination of colistin resistance. This highlights the urgent need for rapid and accessible screening methods to detect and control the spread of mcr-1-mediated colistin resistance.
Researchers have developed a novel phenotypic method called the Colistin-MAC test, designed for quick and easy screening of MCR-1-mediated colistin resistance. This test leverages the synergy between colistin and dipicolinic acid (DPA) to identify resistant strains, offering a promising tool for combating antibiotic resistance.
The Growing Burden
Colistin resistance is part of a wider antimicrobial-resistance crisis. A 2025 analysis reported colistin resistance in 3.98% of the strains examined, including 4.80% of Escherichia coli, 5.43% of Enterobacter spp., and 0.31% of Citrobacter spp. The CDC reports that more than 2.8 million antimicrobial-resistant infections occur annually in the United States and that more than 35,000 people die as a result, while WHO reports that approximately one in six laboratory-confirmed bacterial infections worldwide was resistant to antibiotics in 2023.
Testing Is Essential but Imperfect
Broth microdilution is the recommended method for detecting colistin resistance, but it is labor-intensive and time-consuming. Research on colistin-susceptibility testing reported low very major error rates of 0.7% and major error rates of approximately 3.7%, while also noting potential limitations. In a phenotypic approach, a strain was classified as resistant when more than one colony grew and susceptible when no growth occurred, illustrating the appeal of simpler tests.
The mcr-1 Milestone
A major milestone came in 2015 with the discovery of mcr-1, the first transferable colistin-resistance gene. The CDC reports that scientists in China described the first instance of this gene in November 2015. The discovery was significant because mcr-1 can confer resistance to colistin, an older antibiotic.
How Does the Colistin-MAC Test Work?
The Colistin-MAC test is a broth microdilution method that assesses colistin MIC (minimum inhibitory concentration) in the absence and presence of dipicolinic acid (DPA). DPA is a chelator that can reduce colistin resistance in MCR-1 producing strains.
- A ≥8-fold reduction of colistin MIC in the presence of DPA was observed with 59 mcr-1-positive strains.
- Colistin MICs were unchanged, increased, or at most reduced by two-fold with the 13 mcr-negative colistin-resistant strains.
A Last-Resort Drug Under Pressure
Recent reviews describe colistin resistance across both clinical and non-clinical settings and emphasize the continuing emergence of new findings. Colistin re-emerged in the mid-1990s as a last-hope treatment against multidrug-resistant Gram-negative pathogens after extensively drug-resistant Gram-negative bacteria became more common. A reported meta-analysis estimated pooled colistin resistance at 13.75% for one key pathogen, underscoring concern about resistance in organisms for which treatment options are already limited.
Resistance Can Worsen Outcomes
Colistin resistance is not simply a laboratory finding; it can undermine the effectiveness of a last-resort therapy. A 2025 review reports that this resistance is associated with higher treatment-failure rates, prolonged hospitalizations, and increased mortality. Other research warns that the evolution of colistin resistance may also increase bacterial virulence and resistance to additional antibiotics, supporting calls for multisectoral research and surveillance.
Balancing Efficacy and Toxicity
Comparisons of colistin treatment strategies highlight an important trade-off. A 2026 systematic review and network meta-analysis found that single-agent colistin therapy consistently produced more nephrotoxicity than alternative or combination regimens. This concern is especially consequential because reviews describe colistin resistance as a major challenge in a setting where few effective antibiotics remain available.
Why This Test Matters for Combating Antibiotic Resistance
The Colistin-MAC test offers a practical solution for identifying and controlling the spread of MCR-1 mediated colistin resistance. Its simplicity and low cost make it accessible to laboratories with limited resources, enabling widespread surveillance and prompt intervention.
Surveillance Must Keep Pace
Colistin has re-emerged as a last-resort antibiotic for infections caused by multidrug-resistant Gram-negative bacilli. That renewed dependence makes resistance surveillance especially important. However, ANSES and the European Medicines Agency have recommended that colistin not yet be included in the list of critically important antimicrobials, showing that expert assessments of its classification and role may still differ.
The Next Testing Frontier
Future work will likely need to make colistin-resistance detection faster, simpler, and reliable enough for routine use. Research may also need to connect phenotypic testing with surveillance of transferable resistance mechanisms such as mcr-1. Because the available evidence points to an evolving threat, these priorities should be treated as directions for research rather than guaranteed solutions.
A Global One-Health Concern
Colistin resistance is described as a mounting global health concern, particularly alongside multidrug-resistant and extensively drug-resistant bacterial infections. Because colistin remains a last-resort antibiotic against multidrug-resistant Gram-negative pathogens, increasing resistance threatens an already narrow treatment reserve. Reported mechanisms include lipid A modifications that help bacteria evade colistin, while associated treatment failure, longer hospitalizations, and increased mortality broaden the consequences beyond the laboratory.
When Resistance Reaches Patients
The human consequences of antimicrobial resistance are illustrated by patient stories in which an experimental antibiotic saved a man's leg and life after an aggressive drug-resistant infection. A large study estimated that antibiotic-resistant bacterial infections directly caused 1.27 million deaths in 2019. These broader antimicrobial-resistance experiences show why preserving effective treatments and identifying resistance early matter to individual patients, not only to surveillance programs.
By quickly identifying mcr-1-positive strains, healthcare professionals can implement targeted infection control measures and optimize antibiotic usage, slowing the spread of resistance. This is particularly crucial in low-income settings where advanced molecular diagnostics are not readily available.
While the Colistin-MAC test shows promise, further research is needed to evaluate its performance across a wider range of bacterial species and resistance mechanisms. Continuous refinement and validation will ensure its effectiveness in the ongoing fight against antibiotic resistance, ultimately safeguarding public health.