Repurposed Antimicrobial Combination Therapy: Tobramycin-Ciprofloxacin Hybrid Augments Activity of the Anticancer Drug Mitomycin C Against Multidrug-Resistant Gram-Negative Bacteria

Domalaon, Ronald; Ammeter, Derek; Brizuela, Marc; Gorityala, Bala Kishan; Zhanel, George G.; Schweizer, Frank

doi:10.3389/fmicb.2019.01556

Cited by 36 publications

(27 citation statements)

References 38 publications

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“…The gradual back off in mono-drug therapy, due to the resistant strain's emergence, made the combination drug therapy a first-line option for better outcomes. The principle of combined drug therapy relies on the simultaneous use of multiple therapeutics called a "drug cocktail" to treat bacterial infections with the goal of achieving synergistic drug effects, combating resistance, minimizing side effects, and expanding antimicrobial spectrum [197,198]. Moreover, the co-encapsulation of the combined drugs within nano-systems will offer advances in managing resistant bacterial infections, however the practical application is still in preliminary stages [199].…”

Section: Nano Systems With Combination Drug Therapymentioning

confidence: 99%

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

et al. 2020

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Based on the recent reports of World Health Organization, increased antibiotic resistance prevalence among bacteria represents the greatest challenge to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of the current antibacterial therapy prompted the researchers to explore new innovative strategies to overcome such resilient microbes. Hence, novel antibiotic delivery systems are in high demand. Nanotechnology has attracted considerable interest due to their favored physicochemical properties, drug targeting efficiency, enhanced uptake, and biodistribution. The present review focuses on the recent applications of organic (liposomes, lipid-based nanoparticles, polymeric micelles, and polymeric nanoparticles), and inorganic (silver, silica, magnetic, zinc oxide (ZnO), cobalt, selenium, and cadmium) nanosystems in the domain of antibacterial delivery. We provide a concise description of the characteristics of each system that render it suitable as an antibacterial delivery agent. We also highlight the recent promising innovations used to overcome antibacterial resistance, including the use of lipid polymer nanoparticles, nonlamellar liquid crystalline nanoparticles, anti-microbial oligonucleotides, smart responsive materials, cationic peptides, and natural compounds. We further discuss the applications of antimicrobial photodynamic therapy, combination drug therapy, nano antibiotic strategy, and phage therapy, and their impact on evading antibacterial resistance. Finally, we report on the formulations that made their way towards clinical application.

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Section: Nano Systems With Combination Drug Therapymentioning

confidence: 99%

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

et al. 2020

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“…In a promising strategy to combat bacterial resistance, antibacterial AAGs have also emerged as adjuvants in combination with existing antibiotics. AG conjugates to an efflux pump inhibitor or to an antibiotic drug of another class (antibiotic hybrids) can promote, as adjuvants, the uptake of antibiotics through the OM of Gram-negative bacteria via the self-promoted uptake mechanism by displacement of the divalent cations (Ca 2+ or Mg 2+ ), which stabilize LPS [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. The high affinity of strongly lipophilic AAGs of the first and second types for nucleic acids was used to develop efficient non-antibacterial vehicles for nucleic acid uptake in mammalian cells [ 129 , 130 , 131 , 132 , 133 , 134 , 135 ].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro screening of six anticancer drugs for their potential use in antimicrobial therapy suggested the feasibility of repurposing the anticancer drug mitomycin C against MDR Gram-negative bacteria [ 111 ]. In combination with the TOB-CIP hybrid 55 ( n = 12, Figure 10 ), the antibacterial activity of mitomycin C was enhanced against MDR clinical isolates of P. aeruginosa , A. baumannii , E. coli , K. pneumoniae and Enterobacter cloacae .…”

Section: Antibacterial Amphiphilic Aminoglycosides (Antibacterial mentioning

confidence: 99%

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Amphiphilic Aminoglycosides as Medicinal Agents

Dezanet

Kempf

Mingeot‐Leclercq

et al. 2020

IJMS

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The conjugation of hydrophobic group(s) to the polycationic hydrophilic core of the antibiotic drugs aminoglycosides (AGs), targeting ribosomal RNA, has led to the development of amphiphilic aminoglycosides (AAGs). These drugs exhibit numerous biological effects, including good antibacterial effects against susceptible and multidrug-resistant bacteria due to the targeting of bacterial membranes. In the first part of this review, we summarize our work in identifying and developing broad-spectrum antibacterial AAGs that constitute a new class of antibiotic agents acting on bacterial membranes. The target-shift strongly improves antibiotic activity against bacterial strains that are resistant to the parent AG drugs and to antibiotic drugs of other classes, and renders the emergence of resistant Pseudomonas aeruginosa strains highly difficult. Structure–activity and structure–eukaryotic cytotoxicity relationships, specificity and barriers that need to be crossed in their development as antibacterial agents are delineated, with a focus on their targets in membranes, lipopolysaccharides (LPS) and cardiolipin (CL), and the corresponding mode of action against Gram-negative bacteria. At the end of the first part, we summarize the other recent advances in the field of antibacterial AAGs, mainly published since 2016, with an emphasis on the emerging AAGs which are made of an AG core conjugated to an adjuvant or an antibiotic drug of another class (antibiotic hybrids). In the second part, we briefly illustrate other biological and biochemical effects of AAGs, i.e., their antifungal activity, their use as delivery vehicles of nucleic acids, of short peptide (polyamide) nucleic acids (PNAs) and of drugs, as well as their ability to cleave DNA at abasic sites and to inhibit the functioning of connexin hemichannels. Finally, we discuss some aspects of structure–activity relationships in order to explain and improve the target selectivity of AAGs.

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“…Different agents are promising both in vitro and in vivo candidates to be repositioned as antimicrobial agents to treat infections caused by MDR Gram-negative bacilli. A variety of drugs with different mechanisms of action and targets have been selected including: DNA, RNA and proteins inhibitors [16][17][18][19][20], QS regulators [15,17,[21][22][23][24][25], biofilm formation inhibitors and disruptors [26,27], drugs that interact with cell membrane [28][29][30], drugs that interact with iron metabolism [31][32][33][34][35], and host immune system modulators [36][37][38][39]. These drugs and their mechanisms of action against critical-priority pathogens (A. baumannii, P. aeruginosa and Enterobacterales) are summarized in Figure 1 and Table 1.…”

Section: Mechanisms Of Action Of Repurposing Drugs Against Gram-negatmentioning

confidence: 99%

Drugs Repurposing for Multi-Drug Resistant Bacterial Infections

Domínguez¹,

Me²,

Smani³

2020

Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications

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Different institutions recognized that antimicrobial resistance is a global health threat that has compounded by the reduction in the discovery and development of new antimicrobial agents. Therefore, the development of new antimicrobial therapeutic strategies requires immediate attention to avoid the 10 million deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacteria. Despite the great interest in the development of repurposing drugs, only few repurposing drugs are under clinical development against Gram-negative criticalpriority pathogens. In this chapter, we aim: (i) to discuss the therapeutic potential of the repurposing drugs for treating MDR bacterial infections, (ii) to summarize their mechanism of action, and (iii) to provide an overview for their preclinical and clinical development against these critical-priority pathogens.

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Repurposed Antimicrobial Combination Therapy: Tobramycin-Ciprofloxacin Hybrid Augments Activity of the Anticancer Drug Mitomycin C Against Multidrug-Resistant Gram-Negative Bacteria

Cited by 36 publications

References 38 publications

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

Amphiphilic Aminoglycosides as Medicinal Agents

Drugs Repurposing for Multi-Drug Resistant Bacterial Infections

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