Challenges in Antibiotic R&D Calling for a Global Strategy Considering Both Short- and Long-Term Solutions

Abstract

showed a lack of novelty and diversity regarding target pathogens and indications and a failure to address the most urgent resistance threats, including resistant Gram-negative bacteria. A global research and development strategy should incentivize development of broad-spectrum antibiotics for critically ill patients, as well as therapeutic alternatives to antibiotics, decreasing our dependence on traditional, small-molecule antibiotics.C oncerns about antimicrobial resistance (AMR) have been voiced since the 1940s when antibiotics were first used to treat patients, 1 but only recently has AMR become recognized as a global health threat. Antibiotic use, an important driver of antibiotic resistance, is increasing globally. This increase is a consequence of rising populations and incomes, and the background burden of infectious disease caused by lack of access to public health, clean water and sanitation. 2 Therefore, in addition to reducing irresponsible and unnecessary use of antibiotics, a crucial part of a global strategy to combat AMR is measures to prevent the development and spread of infectious diseases, including through incentives for new antibiotics and vaccines. 3 Antibiotic development has slowed considerably during the past 30 years, with few new antibiotics reaching the market. 4 Reasons for this decline include scientific challenges to discovering new antibiotic compounds and bacterial targets, barriers to successfully conducting clinical trials, high levels of competition from already approved antibiotics, and the risk that new antibiotics will become inefficient within a few years of market entry due to resistance. 5,6 A recent analysis of antibiotics for systemic use approved between 1999 and 2014, conducted by researchers at the

Antibiotics and Bacterial Resistance—A Short Story of an Endless Arms Race

“…In fact, the number of new antibiotics reaching the market has considerably decreased in the last 30 years. A lack of diversity and novelty in antibiotic R&D has also been reported throughout the last few decades [ 293 , 294 , 295 ]. However, this has resulted from economic rather than scientific problems, since for big pharmaceutical companies, other drugs, such as cancer drugs, are much more profitable than antibiotics [ 295 ].…”

Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies

“…It was suggested to apply therapeutic alternatives to antibiotics that would decrease our dependence on traditional antibiotics. The fact that antibiotic effectiveness is reduced over time due the potential development of resistance, new antibiotics will always be needed [55].…”

Bioactive Metabolites of Marine Origin Have Unusual Effects on Model Membrane Systems

“…The scientific and commercial interest for finding new compounds with antibiotic and antineoplastic properties has increased in the last two decades as antibiotic and multi-drug resistance in cancer remains a pressing societal challenge [1][2][3][4]. Approaches to meet this challenge include producing analogs of existing compounds and designing new compounds that interfere with the cellular processes that are required for proliferation [1,5].…”

“…These analogs simplified the side chains and also involved modifications in the adenine ring [15][16][17][18][19][20]. Data for analogs (2)(3)(4) are shown in Table 1. We have also previously reported the first total synthesis of a malonganenone J (5) [21] and evaluated its biological activity (Table 1).…”

“…It has also been documented that transferring oleic acid to the cell membrane using protein fatty-acid complexes, liprotides, cause cancer cell death through disruptive effects on the membranes [34,35]. These phenomena, along with recent evidence indicating that even small changes to the composition of lipid systems may have a pronounced effect on their phase behavior [29,[36][37][38], prompted us to investigate malonganone J, agelasine D, and agelasine analogs using hydrated dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) model lipid systems doped with these compounds (1)(2)(3)(4)(5).…”