Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review.

Taryn A Eubank,Julian G Hurdle,Kevin W Garey,Anne J Gonzales-Luna

doi:10.3390/antibiotics11020258

Taryn A Eubank, Julian G Hurdle + Show 2 more

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https://doi.org/10.3390/antibiotics11020258

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Abstract

Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in C. difficile, including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact.

Highlights

Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the United States with an estimated 223,900 cases in hospitalized patients and 12,800 associated deaths in 2017 [1,2]
For more than four decades, metronidazole and vancomycin have been the leading antimicrobial therapies for CDI, with fidaxomicin indicated for use
As few antibiotic treatment options are available for CDI, an increasing amount of selection pressure is placed on the development of antibiotic resistance

Summary

Introduction

Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the United States with an estimated 223,900 cases in hospitalized patients and 12,800 associated deaths in 2017 [1,2]. For more than four decades, metronidazole and vancomycin have been the leading antimicrobial therapies for CDI, with fidaxomicin indicated for use. Resistance to other antibiotics used to treat CDI, namely metronidazole, has been identified, leading to the question of whether C. difficile may evolve clinically meaningful resistance to vancomycin [6,7,8]. Prescription rates for oral vancomycin increased following the 2017 IDSA/SHEA recommendation of vancomycin as first-line therapy for CDI [9]. This likely increased the selection pressure for the spread of vancomycin-resistant C. difficile

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