Molecular epidemiology of bacteraemic vancomycin-resistant Enterococcus faecium isolates and in vitro activities of SC5005 and other comparators against these isolates collected from a medical centre in northern Taiwan, 2019-2020.

Abstract

The global prevalence of vancomycin-resistant Enterococcus faecium (VREfm) highlights the need for new anti-enterococcal agents. Here, we assessed the molecular epidemiology of clinical VREfm bacteraemic isolates from a medical centre in northern Taiwan in 2019-2020 and to evaluate their susceptibility to last-line antibiotics and a new antimicrobial agent, SC5005. The molecular epidemiology of VREfm was investigated using van genotyping, MLST and PFGE. The susceptibilities of VREfm strains to antibiotics and SC5005 were determined using the agar dilution and broth microdilution methods. The capability of E. faecium to develop resistance to antibiotics and SC5005 was evaluated using frequency of resistance and multipassage resistance assays. The mode of action of SC5005 was assessed by time-kill, bacterial membrane integrity and membrane potential assays. All 262 VREfm isolates harboured vanA gene, and the most prevalent sequence type was ST17 (51%, n = 134, 84 pulsotypes), followed by ST78 (25%, n = 65, 54 pulsotypes). Additionally, we identified four new STs (ST2101, ST2102, ST2135 and ST2136) and observed the arrival of multidrug-resistant ST1885 in Taiwan. Moreover, SC5005 was effective against all VREfm isolates, including those non-susceptible to last-line antibiotics. SC5005 can disrupt and depolarize the bacterial membrane to kill E. faecium without detectable resistance. The findings provide insights into the latest epidemiology and resistance profiles of bacteraemic-causing VREfm in northern Taiwan. Additionally, SC5005 has the potential for development as a new therapeutic to treat VREfm infections.