Daptomycin is a lipopeptide antibiotic with rapid bactericidal activity against Gram-positive bacteria [1]. Daptomycin has in vitro activity against enterococci, staphylococci, streptococci, corynebacteria, and stationary-phase persistent bacteria Borrelia burgdorferi [2]. The antibacterial mechanism of daptomycin is different from that of most antibiotics. It uses acylglycerol phosphate to insert into the cell membrane and agglomerate, change the curvature of the cell membrane and perforate it, thereby triggering cell depolarization and leading to cell necrosis [3].
In vitro, Daptomycin(5μg/ml) reduces Staphylococcus aureus cell viability by >99% and membrane potential by >90% within 30 minutes[4]. Daptomycin (100 μg/ml) treated high-density exponentially growing Staphylococcus aureus ATCC 29213 cells for 60 minutes and had a very rapid bactericidal effect, reducing the number of bacteria by 3 logs[5].
In vivo, Daptomycin (20 mg/kg; i.p.) significantly improved the survival rate and reduced the number of viable bacteria and the level of neutrophil chemotactic factor KC in the peritoneal fluid 6h after treatment of peritonitis mice inoculated with enterococci.[6]. Daptomycin (60 mg/kg; s.c.) has moderate efficacy in the treatment of Staphylococcus aureus osteomyelitis in Sprague-Dawley CD rats [7].
References:
[1]Steenbergen J N , Jeff A , Thorne G M ,et al.Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections[J].Journal of Antimicrobial Chemotherapy2005(3):283-8.
[2] Feng J, Weitner M, Shi W, et al. Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime[J].Frontiers in Microbiology. 2016, 7: 62.
[3] Pogliano J, Pogliano N, Silverman JA. Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins. Journal of Bacteriology[J].September 2012, 194 (17): 4494–504.
[4] Silverman, Jared A, Perlmutter, et al. Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus[J].Antimicrob Agents Chemother. 2003 Aug;47(8):2538-44.
[5] Mascio C T M , Alder J D , Silverman J A. Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells[J]. Antimicrobial Agents and Chemotherapy, 2007, 51(12): 4255-4260.
[6]Kajihara T1, Nakamura S2, Iwanaga N3, et al. Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis. J Infect Chemother. 2017 Jul;23(7):498-501.
[7]Poeppl W , Tobudic S , Lingscheid T ,et al. Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model[J].Antimicrobial Agents and Chemotherapy, 2011, 55(11):4999-5003.