Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens

Abstract

Antibiotics, which hit the market with astounding impact, were once called miracle drugs, as these were considered the ultimate cure for infectious diseases in the mid-20th century. However, today, nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperiling the foundation of modern medicine. During the COVID-19 pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance (AMR). Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against multidrug-resistant (MDR) pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.

Research Progress on the Combination of Quorum-Sensing Inhibitors and Antibiotics against Bacterial Resistance

“…However, with the emergence of drug-resistant bacteria, macrolides have also fallen to the altar. Fortunately, the emergence of antibacterial synergists may save the status of macrolides [55]. In particular, QSIs have the potential to become antibacterial synergists, and combination therapy is likely to become a new means of combating bacterial resistance [56,57].…”

“…The synergistic antibacterial potential of the oxazolidinone derivative 30 with MEPM has been previously illustrated. Here, a series of benzoxazolone derivatives were further designed and synthesized, and the synergistic antibacterial effects of multiple compounds (49)(50)(51)(52)(53)(54)(55) with antibiotics were explored. The results showed that the combination of 49-55 (32 µg mL −1 ) with CIP (0.2 µg mL −1 ) or CLA (3.2 µg mL −1 ) significantly increased the mortality of P. aeruginosa PAO1.…”