Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Cui, Ze-Hua; He, Hui-Ling; Zheng, Zi-Jian; Yuan, Zhaoqi; Chen, Ying; Huang, Xinyi; Ren, Hao; Zhou, Yu; Zhao, Dong-Hao; Fang, Liang‐Xing; Yu, Yang; Liu, Yahong; Liao, Xiao‐Ping; Sun, Jian

doi:10.3390/antibiotics12040760

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Phentolamine combined with the macrolide antibiotics erythromycin, clarithromycin, and azithromycin indicated a synergistic action against many Gramnegative isolates such as E. coli, S. typhimurium, K. pneumoniae, and A. baumannii . The fractional concentration inhibitory indices (FICI) of 0.375 and 0.5 indicated a synergic effect that was consistent with kinetic time-kill assays and the strong synergism has also been observed in the Galleria mellonella model [61].…”

Section: Synthetic Potentiatorssupporting

confidence: 70%

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

PAUL,

Chawla,

Ahrodia

et al. 2023

Preprint

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Antibiotics were once called miracle drugs which hit the market with astounding impact as it was 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, imperilling the foundation of modern medicine. During the COVID 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. Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against 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.

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Section: Synthetic Potentiatorssupporting

confidence: 70%

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

PAUL,

Chawla,

Ahrodia

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Phentolamine combined with the macrolide antibiotics erythromycin, clarithromycin, and azithromycin indicated a synergistic action against many Gram-negative isolates such as E. coli, S. typhimurium, K. pneumoniae, and A. baumannii. The fractional concentration inhibitory indices (FICI) of 0.375 and 0.5 indicated a synergic effect that was consistent with kinetic time-kill assays and a strong synergism has also been observed in the Galleria mellonella model [100].…”

Section: Synthetic Potentiatorssupporting

confidence: 68%

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

Paul,

Chawla,

Ahrodia

et al. 2023

Antibiotics

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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.

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Section: The Role Of Efflux Pump Inhibitors In Reversing Drug Resistancementioning

confidence: 99%

“…The compound has been successfully used in the treatment of cocaine-induced cardiovascular complications to counteract serious peripheral vasoconstriction and pain caused by the infusion of vasopressors. Numerous investigations and clinical data confirm its safety profile, and its reversal of resistance to macrolide antibiotics highlights its potential as an efflux pump inhibitor [77]. Cui et al combined phentolamine (Figure 5) with the macrolide antibiotics azithromycin, clarithromycin, and erythromycin and found a synergistic effect on E. coli test strains, as indicated by a fractional concentration inhibition index (FICI) of 0.375-0.5.…”

Section: Escherichia Coli Efflux Pump Inhibitorsmentioning

confidence: 99%

Bacterial Efflux Pump Inhibitors Reduce Antibiotic Resistance

Zhang,

Tian,

Sun

et al. 2024

Pharmaceutics

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Bacterial resistance is a growing problem worldwide, and the number of deaths due to drug resistance is increasing every year. We must pay great attention to bacterial resistance. Otherwise, we may go back to the pre-antibiotic era and have no drugs on which to rely. Bacterial resistance is the result of several causes, with efflux mechanisms widely recognised as a significant factor in the development of resistance to a variety of chemotherapeutic and antimicrobial medications. Efflux pump inhibitors, small molecules capable of restoring the effectiveness of existing antibiotics, are considered potential solutions to antibiotic resistance and have been an active area of research in recent years. This article provides a review of the efflux mechanisms of common clinical pathogenic bacteria and their efflux pump inhibitors and describes the effects of efflux pump inhibitors on biofilm formation, bacterial virulence, the formation of bacterial persister cells, the transfer of drug resistance among bacteria, and mismatch repair. Numerous efforts have been made in the past 20 years to find novel efflux pump inhibitors which are known to increase the effectiveness of medicines against multidrug-resistant strains. Therefore, the application of efflux pump inhibitors has excellent potential to address and reduce bacterial resistance.

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Phentolamine Significantly Enhances Macrolide Antibiotic Antibacterial Activity against MDR Gram-Negative Bacteria

Cited by 8 publications

References 32 publications

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

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

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

Bacterial Efflux Pump Inhibitors Reduce Antibiotic Resistance

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