Challenges in the Detection of Polymyxin Resistance: From Today to the Future

Abstract

Antimicrobial resistance is known to be one of the greatest global threats to human health, and is one of the main causes of death worldwide. In this scenario, polymyxins are last-resort antibiotics to treat infections caused by multidrug-resistant bacteria. Currently, the reference test to evaluate the susceptibility of isolates to polymyxins is the broth microdilution method; however, this technique has numerous complications and challenges for use in laboratory routines. Several phenotypic methods have been reported as being promising for implementation in routine diagnostics, including the BMD commercial test, rapid polymyxin NP test, polymyxin elution test, culture medium with polymyxins, and the Polymyxin Drop Test, which require materials for use in routines and must be easy to perform. Furthermore, Sensititre®, molecular tests, MALDI-TOF MS, and Raman spectroscopy present reliable results, but the equipment is not found in most microbiology laboratories. In this context, this review discusses the main laboratory methodologies that allow the detection of resistance to polymyxins, elucidating the challenges and perspectives.

A Review on Colistin Resistance: An Antibiotic of Last Resort

“…A positive result, indicating polymyxin resistance, manifests as a color change to yellow due to bacterial growth in the presence of polymyxin, signifying carbohydrate/glucose metabolism. Conversely, a negative result occurs when the color remains orange, denoting the absence of bacterial growth [5].…”

“…After that, plates are incubated for 16 to 18 h at 35 • C following a 15 min rest period at room temperature. After incubation, isolates are characterized by the absence or presence of a zone [5]. In a different investigation, the effectiveness of the Drop Test in identifying Enterobacterales and non-fermenting Gram-negative bacilli resistant to carbapenems with polymyxin B resistance was assessed.…”

“…Despite many drawbacks, including decreased sensitivity and specificity in cases where the sample contains multiple mcr genes, the likelihood of a single strain containing numerous mcr genes is low, making this approach applicable in practical scenarios. Moreover, the method's rapidity, with a total operating time of less than 60 min, and user-friendly nature with no specialized instrument requirements, underscore its potential as a near-patient screening test [5].…”

“…Polymyxin E, another name for colistin, is a polycationic antibiotic renowned for its efficacy against Gram-negative bacteria, particularly Enterobacteriaceae. Resistance to colistin primarily arises from chromosomal mutations, which modify the lipid A component of bacterial lipopolysaccharide, reducing its interaction with colistin through cationic substitutions [5]. Thus, the main target of colistin is the lipopolysaccharide found in Gramnegative bacteria's outer cell membrane.…”