Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

Abstract

Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.

Berberine Hydrochloride Could Prove to Be a Promising Bullet Against Clostridium Difficile Infection: A Preliminary Study From South India

“…We propose that owing to the antibacterial as well as anti-inflammatory properties, BBRHCl bypasses the multifactorial mechanisms of resistance (adopted by C. difficile) which are otherwise effective against standard antibiotics. Inhibition of Gram-positive bacterial sortase by berberine can be attributed partially to its direct antibacterial activity toward toxigenic C. difficile [22]. Berberine's mechanism of action is different when compared to metronidazole and vancomycin as mentioned earlier [2,4].…”

“…This fact is of particular importance when considering various drug combinations (example non-antibiotic candidate drug with an antibiotic) where literature reports say that successful combinations can be achieved if the combination partner acts on a different molecule than that of the antibiotic [22]. Moreover, due to its anti-inflammatory activity by antagonizing lipopolysaccharide signaling, decreasing neutrophil infiltration and downregulating proinflammatory genes subsequent to TLR4-MD2 binding and inhibition of TLR4-NF-κB-MIP2, respectively, berberine qualifies as a more potent alternative to metronidazole and vancomycin in CDI management [22].…”

Antimicrobial resistance and the race to find new antibiotics

“…But his Perspectives paper in Nature Reviews Drug Discovery shows that a range of drugs can syner gise with existing antibiotics and make them more effective against multidrug resistant bacteria. 6 It is termed a 'salvage' operation; injecting added efficacy into an exist ing class while new discoveries, which "could take decades", are developed. The paper states: "As an interim solu tion, antibiotic resistance could be 'bro ken' by co administering appropriate nonantibiotic drugs with failing antibiot ics.…”

Pharmakotherapie bei Neonaten und Jungtieren

“…bei der Septikämie des neugeborenen Fohlens, für die Mortalitätsraten von bis zu 68% beschrieben sind [4][5][6]; diesbezüglich stellt auch der Einsatz von Arzneipflanzen eine Möglichkeit dar [7][8][9]. Ein weiterer Aspekt besteht in der Aktivierung antimikrobieller Peptide bei Jungtieren [10][11][12][13][14][15].…”