Background: The emergence and spread of linezolid-resistant Enterococcus faecalis  (E. faecalis ) have emerged as a serious threat to human health globally. Therefore, this study aims to compare the anti-microbic as well as the anti-biofilm activity of linezolid, tedizolid, and radezolid against linezolid-resistant E. faecalis .
Methods: A total of 2128 E. faecalis  isolates were assessed from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2019. Antibiotic sensitivity was evaluated using the micro broth dilution method. Oxazolidinone-resistant chromosomal and plasmid-borne genes such as cfr, cfr(A), cfr(B), cfr(C), cfr(D), optrA , and poxtA  were detected by PCR and then sequenced to detect the presence of mutations in the domain V of the 23S rRNA and the ribosomal proteins L3, L4, and L22. Conjugation experiments were conducted using the broth method. The inhibition and eradication of biofilm were evaluated through crystal violet staining, whereas the efflux pump activities were detected by agar dilution.
Results: Out of 2128 isolated E. faecalis , 71 (3.34%) were linezolid-resistant isolates in which the MICs of tedizolid and radezolid ranged from 1 to 4 μg/mL and 0.5– 1 μg/mL, respectively. The MIC₅₀/MIC₉₀ of tedizolid and radezolid were 4 and 8-fold lower than the linezolid, respectively. Out of 71 resistant isolates, 57 (80.28%) carried optrA , 1 (1.41%) carried cfr , 4 (5.63%) carried optrA  and cfr , and 6 (8.45%) carried optrA  and cfr(D) , with no mutations of 23S rRNA gene and ribosomal proteins L3, L4, and L22. Besides, the transfer rate of the optrA, cfr , and cfr(D)  was 17.91%, 0% and 0%, respectively. Radezolid showed more effectiveness in eradicating biofilm (8 × MIC). However, tedizolid was more effective than radezolid and linezolid in inhibiting the biofilm formation (1/4 MIC, 1/8MIC, and 1/16MIC). Additionally, in combination with CCCP, the MICs of radezolid in all linezolid-resistant isolates decreased ≥ 4-fold.
Conclusion: Radezolid showed greater antimicrobial activity than tedizolid and linezolid against linezolid-resistant E. faecalis . However, both tedizolid and radezolid showed differential activity on biofilm inhibition, eradication, and efflux pump compared to linezolid. Thus, our study might bring important clinical value in the application of these drugs for resistant pathogenic strains.
Keywords: Enterococcus faecalis , linezolid, tedizolid, radezolid, in vitro activity, anti-biofilm activity