Abstract
To find a therapeutic alternative for the treatment of skin and soft tissue infections, we evaluated the effects of combinations of retapamulin with macrolide, lincosamide, and streptogramin (MLS) antibiotics against Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecium, and Enterococcus faecalis. Using both the disk diffusion test and checkerboard assay, we initially examined the effects of combinations of retapamulin with MLS antibiotics against standard strains of these species. Combinations of retapamulin with erythromycin, quinupristin/dalfopristin and quinupristin showed synergistic activity against E. faecalis only. Synergy of retapamulin with clindamycin and dalfopristin was not observed. Then, a checkerboard assay was performed to evaluate the effects of the combinations against 15 clinical strains of E. faecalis. Retapamulin and quinupristin, the most synergistic combination, showed activity against all erythromycin-susceptible, -intermediate, and -resistant strains tested. Among the eight strains with high-level erythromycin resistance, five strains were synergistically inhibited in the presence of only 1 μg of retapamulin per ml. Time-kill assay revealed that combinations of retapamulin with erythromycin and quinupristin were bacteriostatic. These results suggest that combinations of retapamulin with erythromycin and quinupristin have in vitro synergistic activity against E. faecalis, including strains with high-level erythromycin resistance.
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References
Higuita NIA, Huycke MM. Enterococcal disease, epidemiology, and implications for treatment. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.
Kristich CJ, Rice LB, Arias CA. Enterococcal infection–treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.
Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanism in enterococcus. Virulence. 2012;3:421–569.
Conly JM, Johnston BL. Mupirocin—are we in danger of losing it?. Can J Infect Dis 2002;13:157–9.
Sood S, Malhotra M, Das BK, Kapil A. Enterococcal infections and antimicrobial resistance. Indian J Med Res. 2008;128:111–21.
Bender JK, Cattoir V, Hegstad K, Sadowy E, Coque TM, Westh H, et al. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: towards a common nomenclature. Drug Resist Update. 2018;40:25–39.
Bai B, Hu K, Zeng J, Yao W, Li D, Pu Z, et al. Linezolid consumption facilitates the development of linezolid resistance in Enterococcus faecalis in a tertiary-care hospital: a 5-year surveillance study. Microb Drug Resist. 2019;25:791–8.
Schwarz S, Shen J, Kadlec K, Wang Y, Michael GB, Feßler AT, et al. Lincosamides, streptogramins, phenicols, and pleuromutilins: mode of action and mechanisms of resistance. Cold Spring Harb Perspect Med. 2016;6:a027037.
Poehlsgaard J, Douthwaite S. The bacterial ribosome as a target for antibiotics. Nat Rev Microbiol. 2005;3:870–81.
Pillai SK, Moellering RCJ, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, editor. Antibiotics in laboratory medicine. 5th ed. Philadelphia: Lippincott Williams and Wilkins; 2005.
Odds FC. Synergy, antagonism, and what the checkerboard puts between them. J Antimicrob Chemother. 2003;52:1.
Traczewski MM, Brown SD. Proposed MIC and disk diffusion microbiological cutoffs and spectrum of activity of retapamulin, a novel topical antimicrobial agent. Antimicrob Agents Chemother. 2008;52:3863–7.
Acknowledgements
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1A6A1A03011325).
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Park, B., Min, YH. In vitro synergistic effect of retapamulin with erythromycin and quinupristin against Enterococcus faecalis. J Antibiot 73, 630–635 (2020). https://doi.org/10.1038/s41429-020-0312-7
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DOI: https://doi.org/10.1038/s41429-020-0312-7