Daptomycin

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.

达托霉素（Daptomycin）是一种脂肽抗生素，对革兰氏阳性菌具有快速的杀菌活性^[1]。达托霉素对肠球菌、葡萄球菌、链球菌、棒状杆菌和静止期伯氏疏螺旋体持留细菌具有体外活性^[2]。达托霉素的抑菌作用机制与大多数抗生素不同，是利用磷酸酰甘油让其插入细胞膜中，并且凝集，改变细胞膜的曲度并穿孔，进而引发细胞去极化导致细胞坏死^[3]。

在体外，达托霉素（5 μg/ml）在30分钟内能够降低金黄色葡萄球菌>99%的细胞活性和>90%的膜电位^[4]。达托霉素（100μg/ml）处理高密度指数生长的金黄色葡萄球菌ATCC 29213细胞60分钟，具有非常快速的杀菌作用，减少了3个对数的细菌数量^[5]。

在体内，达托霉素（20mg/kg; i.p.）治疗接种肠球菌后的腹膜炎小鼠6h后，显著提高了存活率，降低了腹腔液中活菌数量和中性粒细胞趋化因子KC水平^[6]。达托霉素（60mg/kg; s.c.）治疗Sprague-Dawley CD大鼠金黄色葡萄球菌骨髓炎的效果一般^[7]。