Dual-function Potentiators That Disable Biofilms And Antibiotic Resistance
University of Oklahoma, Norman, OK, USA.
BACKGROUND - Biofilms and antimicrobial resistance create substantial technological barriers to treating chronic wound infections. We have developed a series of dual-function potentiators that disrupt biofilms and also counteract β-lactam resistance mechanisms in staphylococci and pseudomonas. We envision wound treatment with topical application of potentiators to disable biofilms and resistance mechanisms. This mitigates concerns about toxicity (which our data show to be low) and differences in the PK/PD of antibiotics and potentiators. In this way, we can fill the technological void because dual-action potentiators that disable biofilms and antibiotic resistance do not exist.
METHODS - Checkerboard assays were used to measure the minimum inhibitory concentration (MIC) and the minimum biofilm eradication concentration (MBEC).
RESULTS - Combinations of a beta-lactam and potentiator kill MRSA, MRSE, Pseudomonas aeruginosa, and their biofilms. Our potentiators lower antibiotic MIC values by a factor of 100. Antibiofilm synergy is created with potentiator and oxacillin. Neither potentiator nor oxacillin treatment could eradicate MRSE biofilms. However, the combination treatment of potentiator + oxacillin could completely eliminate the recalcitrant biofilms by 10,000-fold CFU reduction.
CONCLUSIONS - A dual-function potentiator may someday markedly change the wound care paradigm by restoring potency to existing antibiotics with a single potentiator. This departs from the status quo of inhibiting biofilms with one compound and targeting resistance with a separate compound.
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