Development of a Broad-Spectrum Antimicrobial Combination for the Treatment of Staphylococcus aureus and Pseudomonas aeruginosa Corneal Infections

Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01929-18. doi: 10.1128/AAC.01929-18. Print 2019 Jan.


Staphylococcus aureus and Pseudomonas aeruginosa are two of the most common causes of bacterial keratitis and corresponding corneal blindness. Accordingly, such infections are predominantly treated with broad-spectrum fluoroquinolones, such as moxifloxacin. Yet, the rising fluoroquinolone resistance has necessitated the development of alternative therapeutic options. Herein, we describe the development of a polymyxin B-trimethoprim (PT) ophthalmic formulation containing the antibiotic rifampin, which exhibits synergistic antimicrobial activity toward a panel of contemporary ocular clinical S. aureus and P. aeruginosa isolates, low spontaneous resistance frequency, and in vitro bactericidal kinetics and antibiofilm activities equaling or exceeding the antimicrobial properties of moxifloxacin. The PT plus rifampin combination also demonstrated increased efficacy in comparison to those of either commercial PT or moxifloxacin in a murine keratitis model of infection, resulting in bacterial clearance of 70% in the animals treated. These results suggest that the combination of PT and rifampin may represent a novel antimicrobial agent in the treatment of bacterial keratitis.

Keywords: Pseudomonas aeruginosa; Staphylococcus aureus; keratitis; polymyxin; rifampin; trimethoprim.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Cornea / drug effects
  • Cornea / microbiology
  • Cornea / pathology
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Synergism
  • Drug Therapy, Combination
  • Eye Infections, Bacterial / drug therapy*
  • Eye Infections, Bacterial / microbiology
  • Eye Infections, Bacterial / pathology
  • Female
  • Humans
  • Keratitis / drug therapy*
  • Keratitis / microbiology
  • Keratitis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Moxifloxacin / pharmacology
  • Ophthalmic Solutions / pharmacology
  • Polymyxin B / pharmacology*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / pathogenicity
  • Rifampin / pharmacology*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / pathogenicity
  • Treatment Outcome
  • Trimethoprim / pharmacology*


  • Anti-Bacterial Agents
  • Ophthalmic Solutions
  • Trimethoprim
  • Polymyxin B
  • Moxifloxacin
  • Rifampin