Current and emerging polymyxin resistance diagnostics: a systematic review of established and novel detection methods

Abstract

AbstractBackgroundThe 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.MethodsA literature search in diverse databases for studies published between 2016 and 2020 was performed. English articles evaluating colistin resistance methods/diagnostics were included.ResultsScreening resulted in the inclusion of 93 journal articles. Current colistin resistance diagnostics are either phenotypic or molecular. Broth microdilution (BMD) 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 (MMS), and ComASP Colistin; automated antimicrobial susceptibility testing (AST) 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 i.e. combined disk test (CDT), modified colistin broth-disk elution (CBDE), Colispot, and Colistin MAC test as well as biochemical colorimetric tests i.e. Rapid Polymyxin NP test and Rapid ResaPolymyxin NP test. Molecular methods only characterize mobile colistin resistance; they include PCR, LAMP, and whole-genome sequencing (WGS).ConclusionDue to the faster turnaround time (≤3h), improved sensitivity (84-100%), and specificity (93.3-100%) of the Rapid ResaPolymyxin NP test, 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.Author summary/highlights/importancePolymyxin resistance is rapidly increasing, threatening public and veterinary healthcare.As one of the last-line antibiotics, polymyxin must be conserved by containing the spread of polymyxin resistance.Detecting colistin resistance relies on determining colistin MIC values by standard broth microdilution, which is labour-intensive with longer turnaround time (TAT).Other polymyxin resistance diagnostics have been developed to augment or replace the broth microdilution with faster TAT.Based on their respective sensitivities, specificities, TAT, skill, and cost, selected phenotypic and molecular assays are recommended for laboratories, according to their financial strengths, to enhance colistin resistance surveillance and control.