Sarecycline Less Damaging to the Human Microbiome Than Other Tetracyclines

Sarecycline is an effective agent for the treatment of acne and further warrants investigation into the potential reduced effects on the gut microbiome.

Sarecycline, a new narrow spectrum tetracycline for the treatment of acne, exhibits targeted efficacy against Cutibacterium acnes and important soft tissue/skin pathogens, while also being 16- to 32-fold less active against the human intestinal microbiome than broad-spectrum tetracyclines, according to a study published in Antimicrobial Agents and Chemotherapy.

Researchers evaluated the spectrum of in vitro activity, in vivo efficacy, potential for resistance development, and mode of action of sarecycline compared with broad-spectrum comparators such as tetracycline, minocycline, and doxycycline against clinical isolates of C acnes and a panel of aerobic and anaerobic bacteria. Investigators sought to demonstrate how sarecycline’s narrow spectrum of activity could result in reduced dysbiosis of intestinal and vaginal flora, and therefore a reduced overgrowth of resistant bacteria, reduced yeast infections, and reduced adverse gastrointestinal effects.

Sarecycline was observed to be between 4- and 8-fold less active against Gram-positive anaerobic bacteria, representative of those comprising the healthy human intestinal microbiome, and between 16- and 32-fold less active against Gram-negative anaerobes.

Furthermore, in a murine septicemia model, reduced activity against Escherichia coli PBS1478 was observed at >40 mg/kg doses for sarecycline, compared with doxycycline and minocycline, which showed protective effects at doses ≤7 mg/kg. Sarecycline also showed a low propensity for C acnes resistance, with spontaneous mutation frequencies similar to vancomycin and minocycline (from 10⁻⁹ to 10⁻¹¹ at 4 to 8 times the minimal inhibitory concentration).

Study investigators concluded that in addition to its efficacy in the treatment of acne, “sarecycline is the first narrow-spectrum tetracycline-derived antibiotic that may reduce the potential for gastrointestinal dysbiosis, adverse effects, and concerns regarding resistance development during therapy.”

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Disclosures: This study was sponsored by Allergan plc. George Zhanel is an investigator and has served as a member of the advisory board for Allergan plc. Lynn-Yao Lin and Nancy Alvandi are employees of Allergan plc. Ian Critchley was an employee of Allergan plc at the time the analysis was conducted. All authors may own stock/stock options in Allergan plc.

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Zhanel G, Critchley I, Lin LY, Alvandi N. Microbiological profile of sarecycline: a novel targeted spectrum tetracycline for the treatment of acne vulgaris [published online November 5, 2018]. Antimicrob Agents Chemother. doi: 10.1128/AAC.01297-18