Comparative Activity of Lipoglycopeptide Antibiotics Against Gram-Positive Bacteria

Lipoglycopeptide antibiotics are semi-synthetic derivatives of glycopeptides and are characterized by a pronounced bactericidal activity against gram-positive pathogens. The aim of the study was comparative assessment of the sensitivity of gram-positive clinical isolates to lipoglycopeptide antibiotics (telavancin, dalbavancin, oritavancin). The following isolates were included in the work: methicillin-resistant Staphylococcus aureus (MRSA, n=780), methicillin-resistant coagulase-negative Staphylococcus spp. (MRCoNS, n=163), and vancomycin-resistant Enterococcus faecium (VREf, n=93). Serial dilutions were used to assess sensitivity with the addition of 0.002% polysorbate 80 to the medium. Lipoglycopeptides showed more pronounced antibacterial activity against MRSA compared to vancomycin, teicoplanin, and daptomycin, and had a MIC₅₀/MIC₉₀ (µg/ml): for telavancin — 0.06 /0.125, for dalbavancin — 0.016/0.06, and for oritavancin — 0.06/0.125. A trend towards an increase in the MIC of lipoglycopeptides and daptomycin was established in MRSA with the MIC of 2 µg/ml for vancomycin, the proportion of which was 13%. For MRCoNS, MIC₅₀ and MIC₉₀ of lipoglycopeptides did not exceed 0.06 µg/ml and 0.125 µg/ml, respectively. Oritavancin showed strong activity against VREf at MIC range of 0.03 µg/ml to 0.5 µg/ml, and at MIC₉₀ of 0.25 µg/ml. Thus, lipoglycopeptide antibiotics are a plausible alternative to vancomycin and daptomycin; they are characterized by pronounced activity and can be used to treat severe forms of staphylococcal infections.

1. Blaskovich M. A. T., Hansford K. A., Butler M. S. et al. Developments in glycopeptide antibiotics. ACS Infect Dis. 2018; 4 (5): 715–735. doi: 10.1021/acsinfecdis.7b00258.

2. Smith J. R., Roberts K. D., Rybak M. J. Dalbavancin: A novel lipoglycopeptide antibiotic with extended activity against gram-positive infections. Infect Dis Ther. 2015; 4 (3): 245–258. doi: 10.1007/s40121-015-0077-7.

3. Karlowsky J. A., Nichol K., Zhanel G. G. Telavancin: mechanisms of action, in vitro activity, and mechanisms of resistance. Clin Infect Dis. 2015; 61: Suppl 2: S58-68. doi: 10.1093/cid/civ534.

4. Binda E., Marinelli F., Marcone G. L. Old and new glycopeptide antibiotics: action and resistance. Antibiotics (Basel). 2014; 3 (4): 572–594. doi: 10.3390/antibiotics3040572.

5. Brade K. D., Rybak J. M., Rybak M. J. Oritavancin: A new lipoglycopeptide antibiotic in the treatment of gram-positive infections. Infect Dis Ther. 2016; 5 (1): 1–15. doi: 10.1007/s40121-016-0103-4.

6. Scoble P. J., Reilly J., Tillotson G. S. Real-world use of oritavancin for the treatment of osteomyelitis. Drugs Real World Outcomes. 2020; 7: Suppl 1: 46–54. doi: 10.1007/s40801-020-00194-8.

7. Lampejo T. Dalbavancin and telavancin in the treatment of infective endocarditis: a literature review. Int J Antimicrob Agents. 2020; 56 (3): 106072. doi: 10.1016/j.ijantimicag.2020.106072.

8. Reilly J., Jacobs M. A., Friedman B. et al. Clinical experience with telavancin for the treatment of patients with bacteremia and endocarditis: realworld results from the Telavancin Observational Use Registry (TOURTM). Drugs Real World Outcomes. 2020; 7 (3): 179–189. doi: 10.1007/s40801-020-00191-x.

9. CLSI. Performance Standards for Antimicrobial Susceptibility Testing M100-Ed32. 2022.

10. Arhin F. F., Sarmiento I., Belley A. et al. Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing. Antimicrob Agents Chemother. 2008; 52 (5): 1597–1603. doi: 10.1128/AAC.01513-07.

11. Kavanagh A., Ramu S., Gong Y. et al. Effects of microplate type and broth additives on microdilution mic susceptibility assays. Antimicrob Agents Chemother. 2019; 63 (1). doi: 10.1128/AAC.01760-18.

12. Pfaller M. A., Sader H. S., Flamm R. K. et al. Oritavancin in vitro activity against gram-positive organisms from European and United States medical centers: results from the SENTRY Antimicrobial Surveillance Program for 2010-2014. Diagn Microbiol Infect Dis. 2018; 91 (2): 199–204. doi: 10.1016/j.diagmicrobio.2018.01.029.

13. Pfaller M. A., Flamm R. K., Castanheira M. et al. Dalbavancin in-vitro activity obtained against Gram-positive clinical isolates causing bone and joint infections in US and European hospitals (2011–2016). Int J Antimicrob Agents. 2018; 51 (4): 608–611. doi: 10.1016/j.ijantimicag.2017.12.011.

14. Duncan L. R., Sader H. S., Huband M. D. et al. Antimicrobial activity of telavancin tested in vitro against a global collection of gram-positive pathogens, including multidrug-resistant isolates (2015–2017). Microb Drug Resist. 2020; 26 (8): 934–943. doi: 10.1089/mdr.2019.0104.

15. Saravolatz L. D., Pawlak J. VISA-Daptomycin non-susceptible Staphylococcus aureus frequently demonstrate non-susceptibility to Telavancin. Diagn Microbiol Infect Dis. 2019; 93 (2): 159–161. doi: 10.1016/j.diagmicrobio.2018.09.003.

16. Werth B. J., Jain R., Hahn A. et al. Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin— and vancomycin-containing regimen. Clin Microbiol Infect. 2018; 24 (4): 429 e1-429 e5. doi: 10.1016/j.cmi.2017.07.028.

17. Steele J. M., Seabury R. W., Hale C. M., Mogle B. T. Unsuccessful treatment of methicillin-resistant Staphylococcus aureus endocarditis with dalbavancin. J Clin Pharm Ther. 2018; 43 (1): 101–103. doi: 10.1111/jcpt.12580.

18. Riccobono E., Giani T., Baldi G. et al. Update on activity of dalbavancin and comparators against clinical isolates of Gram-positive pathogens from Europe and Russia (2017–2018), and on clonal distribution of MRSA. Int J Antimicrob Agents. 2022; 59 (2): 106503. doi: 10.1016/j.ijantimicag.2021.106503.

19. Kaushal R., Hassoun A. Successful treatment of methicillin-resistant Staphylococcus epidermidis prosthetic joint infection with telavancin. J Antimicrob Chemother. 2012; 67 (8): 2052-2053. doi: 10.1093/jac/dks165.

20. Bouza E., Valerio M., Soriano A. et al. Dalbavancin in the treatment of different gram-positive infections: a real-life experience. Int J Antimicrob Agents. 2018; 51 (4): 571–577. doi: 10.1016/j.ijantimicag.2017.11.008.

21. Bender J. K., Cattoir V., Hegstad K. et al. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature. Drug Resist Updat. 2018; 40: 25–39. doi: 10.1016/j.drup.2018.10.002.

22. Li L., Higgs C., Turner A. M. et al. Daptomycin resistance occurs predominantly in vana-type vancomycin-resistant Enterococcus faecium in Australasia and Is associated with heterogeneous and novel mutations. Front Microbiol. 2021; 12: 749935. doi: 10.3389/fmicb.2021.749935.

23. Casapao A. M., Kullar R., Davis S. L. et al. Multicenter study of high-dose daptomycin for treatment of enterococcal infections. Antimicrob Agents Chemother. 2013; 57 (9): 4190–4196. doi: 10.1128/AAC.00526-13.

24. Johnson J. A., Feeney E. R., Kubiak D. W., Corey G. R. Prolonged use of oritavancin for vancomycin-resistant Enterococcus faecium prosthetic valve endocarditis. Open Forum Infect Dis. 2015; 2 (4): ofv156. doi: 10.1093/ofid/ofv156.

25. Belley A., Lalonde-Seguin D., Arhin F. F., Moeck G. Comparative pharmacodynamics of single-dose oritavancin and daily high-dose daptomycin regimens against vancomycin-resistant Enterococcus faecium isolates in an in vitro pharmacokinetic/pharmacodynamic model of infection. Antimicrob Agents Chemother. 2017; 61 (10): e01265-17. doi: 10.1128/AAC.01265-17.

26. Meyer K. A., Deraedt M. F., Harrington A. T. et al. Efficacy of oritavancin alone and in combination against vancomycin-susceptible and -resistant enterococci in an in-vivo Galleria mellonella survival model. Int J Antimicrob Agents. 2019; 54 (2): 197–201. doi: 10.1016/j.ijantimicag.2019.04.010.