Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 73, Issue 12, Pages 3359-3367Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dky330
Keywords
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Funding
- University Paris-Sud, France
- French National Research Agency [ANR-10-LABX-33]
- People Programme (Marie Sklodowska-Curie Actions) of the European Union's Horizon 2020 under REA grant [654909]
- University Paris Sud
- MRC Career Development Award [MR/M009505/1]
- MRC Confidence in Concept Award [RSPO_P54990]
- BBSRC [BB/R00174X/1] Funding Source: UKRI
- MRC [MC_PC_15028, MR/M009505/1, MR/P028225/1] Funding Source: UKRI
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Background: Polymyxins are currently considered a last-resort treatment for infections caused by MDR Gram-negative bacteria. Recently, the emergence of carbapenemase-producing Enterobacteriaceae has accelerated the use of polymyxins in the clinic, resulting in an increase in polymyxin-resistant bacteria. Polymyxin resistance arises through modification of lipid A, such as the addition of phosphoethanolamine (pETN), The underlying mechanisms involve numerous chromosome-encoded genes or, more worryingly, a plasmid-encoded pETN transferase named MCR. Currently, detection of polymyxin resistance is difficult and time consuming. Objectives: To develop a rapid diagnostic test that can identify polymyxin resistance and at the same time differentiate between chromosome-and plasmid-encoded resistances. Methods: We developed a MALDI-TOF MS-based method, named the MALDIxin test, which allows the detection of polymyxin resistance-related modifications to lipid A (i.e. pETN addition), on intact bacteria, in <15 min. Results: Using a characterized collection of polymyxin-susceptible and-resistant Escherichia coif, we demonstrated that our method is able to identify polymyxin-resistant isolates in 15 min whilst simultaneously discriminating between chromosome-and plasmid-encoded resistance, We validated the MALDIxin test on different media, using fresh and aged colonies and show that it successfully detects all MCR-1 producers in a blindly analysed set of carbapenemase-producing E. coif strains. Conclusions: The MALDIxin test is an accurate, rapid, cost-effective and scalable method that represents a major advance in the diagnosis of polymyxin resistance by directly assessing lipid A modifications in intact bacteria.
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