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Jia A. Mei, William Johnson, Bailey Kinn, Emily Laskey, Lydia Nolin, Pratham Bhamare, Charlotte Stalker, Paul M. Dunman, Rachel A. F. Wozniak; Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates. Trans. Vis. Sci. Tech. 2022;11(5):26. doi: https://doi.org/10.1167/tvst.11.5.26.
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Pseudomonas aeruginosa is a leading cause of corneal infections. Recently, we discovered an antimicrobial drug combination, polymyxin B/trimethoprim (PT) + rifampin, that displayed impressive efficacy toward P. aeruginosa in both in vitro and in vivo studies. As such, this combination was further evaluated as a potential keratitis therapeutic through testing the combination's efficacy against a diverse set of P. aeruginosa clinical isolates.
Minimum inhibitory concentrations (MICs) of moxifloxacin, levofloxacin, erythromycin, tobramycin, PT, polymyxin B (alone), trimethoprim (alone), and rifampin were determined for 154 ocular clinical P. aeruginosa isolates, 90% of which were derived from corneal scrapings. Additionally, the efficacy of PT + rifampin was evaluated utilizing fractional inhibitory concentration (FIC) testing.
While 100% of isolates were resistant to erythromycin (average MIC 224 ± 110 µg·mL−1) and trimethoprim (alone) (206 ± 67.3 µg·mL−1), antibiotic resistance was generally found to be low: moxifloxacin (2% of isolates resistant; average MIC 1.08 ± 1.61 µg·mL−1), levofloxacin (3.9%; 1.02 ± 2.96 µg·mL−1), tobramycin (1%; 0.319 ± 1.31 µg·mL−1), polymyxin B (0%; 0.539 ± 0.206 µg·mL−1), PT (0%; 0.416 ± 0.135 µg·mL−1), and rifampin (0%; 23.4 ± 6.86 µg·mL−1). Additionally, FIC testing revealed that PT + rifampin eradicated 100% of isolates demonstrating additive or synergistic activity in 95% of isolates (average FIC index 0.701 ± 0.132).
The drug combination of PT + rifampin was effective against a large panel of clinically relevant P. aeruginosa strains and, as such, may represent a promising therapeutic for P. aeruginosa keratitis.
This work furthers the preclinical development of a novel antibiotic combination for the treatment of corneal infections (bacterial keratitis).
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