Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris

Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01297-18. doi: 10.1128/AAC.01297-18. Print 2019 Jan.

Abstract

Sarecycline is the first narrow-spectrum tetracycline-class antibiotic being developed for acne treatment. In addition to exhibiting activity against important skin/soft tissue pathogens, sarecycline exhibits targeted antibacterial activity against clinical isolates of Cutibacterium acnes In the current study, sarecycline was 16- to 32-fold less active than broad-spectrum tetracyclines-such as minocycline and doxycycline-against aerobic Gram-negative bacilli associated with the normal human intestinal microbiome. Also, reduced activity against Escherichia coli was observed in vivo in a murine septicemia model, with the 50% protective doses, or the doses required to achieve 50% survival, being >40 mg/kg of body weight and 5.72 mg/kg for sarecycline and doxycycline, respectively. Sarecycline was also 4- to 8-fold less active than doxycycline against representative anaerobic bacteria that also comprise the normal human intestinal microbiome. Additionally, C. acnes strains displayed a low propensity for the development of resistance to sarecycline, with spontaneous mutation frequencies being 10-10 at 4 to 8 times the MIC, similar to those for minocycline and vancomycin. When tested against Gram-positive pathogens with defined tetracycline resistance mechanisms, sarecycline was more active than tetracycline against tet(K) and tet(M) strains, with MICs ranging from 0.125 to 1.0 μl/ml and 8 μl/ml, respectively, compared with MICs of 16 to 64 μl/ml and 64 μl/ml for tetracycline, respectively. However, sarecycline activity against the tet(K) and tet(M) strains was decreased compared to that against the wild type, which demonstrated MICs ranging from 0.06 to 0.25 μl/ml, though the decrease in the activity of sarecycline against the tet(K) and tet(M) strains was not as pronounced as that of tetracycline. These findings support sarecycline as a narrow-spectrum tetracycline-class antibiotic that is effective for the treatment of acne, and further investigation into the potential reduced effects on the gut microbiome compared with those of other agents is warranted.

Keywords: Propionibacterium acnes; acne vulgaris; antibiotics; doxycycline; microbiological profile; microbiome; minocycline; sarecycline; tetracycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Acne Vulgaris / microbiology
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Doxycycline / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Escherichia coli / drug effects
  • Female
  • Humans
  • Membrane Proteins / genetics
  • Mice
  • Microbial Sensitivity Tests
  • Propionibacteriaceae / drug effects*
  • Propionibacteriaceae / genetics
  • Propionibacterium acnes / drug effects*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / isolation & purification
  • Tetracycline / pharmacology
  • Tetracyclines / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Proteins
  • Tet M resistance protein, Bacteria
  • Tetracyclines
  • tet(K) protein, Staphylococcus aureus
  • sarecycline
  • Tetracycline
  • Doxycycline

Supplementary concepts

  • Cutibacterium acnes subsp. acnes