Potent Rifampicin Derivatives Can Clear MRSA Infections At Single Low Doses When Concomitantly Dosed With Vancomycin

The emergence of multidrug-resistant bacteria has rendered existing antibiotics increasingly ineffective, posing a critical threat to global health. This necessitates the urgent development of novel antimicrobial agents. Our study identifies a potent macrocycle derivative with remarkable efficacy against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo. In combination with the standard-of-care antibiotic vancomycin, this derivative eradicates MRSA infections in mice at sub-detectable levels.

Traditionally, natural products have served as a rich source for antibiotic discovery. This lineage continues with our identification of promising rifampicin-based analogs exhibiting synergistic activity with vancomycin. Unlike conventional rifampicin derivatives, these novel compounds demonstrate superior potency against MRSA at significantly lower doses, potentially mitigating concerns regarding drug-drug interactions. Notably, their intracellular activity surpasses that of rifampicin, suggesting broader applicability against bacterial pathogens.

The encouraging preclinical results warrant further investigation and development of these promising therapeutics. However, transitioning these discoveries into readily available clinical treatments necessitates collaborative efforts within the pharmaceutical industry. By addressing the current AMR crisis, these novel antibiotics hold significant potential to safeguard human health in the face of increasingly resistant bacterial threats.