Broad-Spectrum Antimicrobial Combination for Corneal Infection Treatment

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Polymxyin B/trimethoprim plus rifampicin was shown to have synergistic antimicrobial activity toward a panel of contemporary ocular clinical isolates of both <i>S aureus</i> and <i>P aeruginosa</i>.
Polymxyin B/trimethoprim plus rifampicin was shown to have synergistic antimicrobial activity toward a panel of contemporary ocular clinical isolates of both S aureus and P aeruginosa.

A combination polymyxin B/trimethoprim ophthalmic formulation containing the antibiotic rifampicin may represent a new antimicrobial agent for the treatment of bacterial keratitis, based on results published in Antimicrobial Agents and Chemotherapy.

Staphylococcus aureus and Pseudomonas aeruginosa, 2 common causes of bacterial keratitis and subsequent corneal blindness, are usually treated with broad-spectrum fourth-generation fluoroquinolones. As a result of increasing fluoroquinolone resistance, investigators are searching for new treatment options.

Study investigators chose polymyxin B/trimethoprim plus rifampicin after screening a library for antibacterial activity against S aureus approved by the United States Food and Drug Administration. The combination was further tested and shown to have synergistic antimicrobial activity toward a panel of contemporary ocular clinical isolates of both S aureus and P aeruginosa. Results also showed low spontaneous resistance frequency as well as in vitro bactericidal kinetics and antibiofilm activities equal to or exceeding those of moxifloxacin. The combination was also found to have increased efficacy in a murine keratitis model when compared with either commercial polymyxin B/trimethoprim or moxifloxacin. The polymyxin B/trimethoprim plus rifampicin combination resulted in bacterial clearance of 70% in the animals treated.

Study investigators concluded that while further characterization is necessary, “rifampicin + [polymyxin B/trimethoprim] may represent a novel antibiotic combination with broad spectrum antimicrobial activity, rapid bactericidal action, anti-biofilm activity, a reduced resistance frequency and potent in vivo activity for the treatment of bacterial keratitis.” They further noted that these results lend further support to the concept that evaluating combinations of drugs approved by the US Food and Drug Administration may be a way forward in the development of novel antimicrobial therapies.

Reference

Chojnacki M, Philbrick A, Wucher B, et al. Development of a broad-spectrum antimicrobial combination for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa corneal infections [published November 12, 2018]. Antimicrob Agent Chemother. doi: 10.1128/AAC.01929-18

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