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Current and emerging polymyxin resistance diagnostics: A systematic review of established and novel detection methods
Tumisho Mmatumelo Seipei Leshaba1, Nontombi Marylucy Mbelle1, John Osei Sekyere1
1Department of Medical Microbiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Abstract:
The emergence of polymyxin resistance, due to transferable mcr genes, threatens public and animal health as there are limited therapeutic options. As polymyxin is one of the last-line antibiotics, there is a need to contain the spread of its resistance to conserve its efficacy. Herein, we describe current and emerging polymyxin resistance diagnostics to inform faster clinical diagnostic choices. A literature search in diverse databases for studies published between 2016 and 2020 was performed. English articles evaluating colistin resistance methods/diagnostics were included. Screening resulted in the inclusion of 93 journal articles. Current colistin resistance diagnostics are either phenotypic or molecular. Broth microdilution is currently the only gold standard for determining colistin MICs (minimum inhibitory concentration). Phenotypic methods comprise of agar-based methods such as CHROMagar™ Col-APSE, SuperPolymyxin, ChromID® Colistin R, LBJMR and LB medium; manual MIC-determiners viz., UMIC, MICRONAUT MIC-Strip and ComASP Colistin; automated antimicrobial susceptibility testing systems such as BD Phoenix, MICRONAUT-S, MicroScan, Sensititre and Vitek 2; MCR-detectors such as lateral flow immunoassay (LFI) and chelator-based assays including EDTA- and DPA-based tests, that is, combined disk test, modified colistin broth-disk elution (CBDE), Colispot, and Colistin MAC test as well as biochemical colorimetric tests, that is, Rapid Polymyxin NP test and Rapid ResaPolymyxin NP test. Molecular methods only characterize mobile colistin resistance; they include PCR, LAMP and whole-genome sequencing. Due to the faster turnaround time (≤3 h), improved sensitivity (84%-100%) and specificity (93.3%-100%) of the Rapid ResaPolymyxin NP test and Fastinov® , we recommend this test for initial screening of colistin-resistant isolates. This can be followed by CBDE with EDTA or the LFI as they both have 100% sensitivity and a specificity of ≥94.3% for the rapid screening of mcr genes. However, molecular assays such as LAMP and PCR may be considered in well-equipped clinical laboratories.
Insights
Polymyxin resistance threatens health, necessitating rapid diagnostics. Emerging tests like Rapid Polymyxin NP offer faster detection of colistin resistance, aiding clinical decisions and preserving antibiotic efficacy.
Area of Science:
- Microbiology and Infectious Diseases
- Clinical Diagnostics
- Antimicrobial Resistance
Background:
- The rise of polymyxin resistance, driven by transferable mcr genes, poses a significant threat to public and animal health due to limited treatment alternatives.
- Polymyxins are last-line antibiotics, making the containment of resistance crucial for preserving their therapeutic value.
Purpose of the Study:
- To review and evaluate current and emerging diagnostic methods for polymyxin resistance.
- To inform clinical choices for faster and more effective diagnosis of colistin resistance.
Main Methods:
- A comprehensive literature search was conducted across diverse databases for studies published between 2016 and 2020.
- Included English articles focused on evaluating colistin resistance methods and diagnostics, resulting in the analysis of 93 journal articles.
- Methods were categorized into phenotypic (agar-based, manual MIC, automated AST, MCR-detectors, biochemical tests) and molecular (PCR, LAMP, WGS).
Main Results:
- Phenotypic methods include gold standard broth microdilution for MICs, various agar-based tests, manual and automated susceptibility testing systems, and rapid MCR-detectors (LFI, chelator-based assays, biochemical tests).
- Molecular methods like PCR, LAMP, and WGS detect mobile colistin resistance genes.
- Rapid Polymyxin NP test and Fastinov® demonstrated superior turnaround time (≤3 h) with high sensitivity (84%-100%) and specificity (93.3%-100%).
Conclusions:
- The Rapid Polymyxin NP test and Fastinov® are recommended for initial screening of colistin-resistant isolates due to their speed and accuracy.
- Modified colistin broth-disk elution (CBDE) with EDTA or lateral flow immunoassay (LFI) are suitable follow-up tests for rapid mcr gene screening, offering 100% sensitivity and high specificity.
- Molecular assays (LAMP, PCR) are viable options for well-equipped clinical laboratories.
