Antibiotic resistance and new types of antimicrobials

Abstract

SummaryThe World Health Organization has pointed out that all current antibiotics exhibit some level of resistance. Moreover, designing new antibiotics to avert resistance is difficult due to the ability of bacteria to mutate targets of current antibiotics. Conceptually, it was realized that to overcome resistance it was necessary to kill bacteria quickly and to avoid mutable targets. New molecules were designed using the fundamentals chemical interactions that would disrupt membrane organization. These small molecules were for both Gram positive and Gram negative bacteria, as well as mouse models of corneal infection. Specific chemical groups were attached to a series of small molecules that resulted in rapid kill time (<60 mins), had no effect on healing of an epithelial wound in rabbits, and in a mouse model of MRSA infection of the cornea were effective at 3 mg/ml compared to vancomycin at 50 mg/ml. Simulation of resistance showed that these new classes of antibiotics did not develop resistance although in the same protocol, MICs for gatifloxicin, gentamycin and norfloxicin increased by 10–140 times. Conclusion: New drug designs based on more predictive behavior could bring a series of new drugs to the clinic to lessen the impact of resistance on healthcare.