Antibiotic Resistance: The Wonder Drugs Facing The Rise Of Superbugs

Antibiotics: the wonder cure, a game-changer for public health

Antibiotics, along with anesthesia and the adoption of hygienic practices by physicians, revolutionized medicine. Introduced 70 years ago, it is widely accepted that antibiotics have been one of the most important factors contributing to the jump in life expectancy observed in the second half of the 20th century in Western countries.

The threat posed by many infectious diseases has been substantially reduced. Even if bacterial infections remain a heavy cause of mortality (roughly 14 million deaths per year worldwide), it is estimated that 548 million bacterial infections are successfully treated every year, including 136 million in Europe.

Antibiotics can also be administered in a prophylactic manner, i.e. to prevent infections. For example, people exposed to bacteriological threats (e.g. the Anthrax episode in the US) or people that will undergo heavy surgeries are administered antibiotics.

How do antibiotics work?

Antibiotics are drugs comprising active molecules effective in killing bacteria. They are most often prescribed by physicians to treat infections by pathogenic bacteria. Basically, most antibiotics rely on the interference with a vital function of the bacteria: when the vital function is disrupted, the bacteria die and the infection is cured.

 

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Whether they are bactericide (killing bacteria) or bacteriostatic (inhibiting the growth of bacteria), antimicrobials are often categorized according to their principal mechanism of action. Classical mechanisms of action include interference with cell membrane synthesis (e.g. beta-lactams and glycopeptide agents) or membrane disruption (polymyxins and daptomycin), inhibition of protein synthesis (macrolides and tetracyclines) or interference with nucleic acid synthesis (fluoroquinolones and rifampin).

Today, the efficacy of antibiotics is seriously endangered

Antibiotics tremendous contribution to modern medicine is now seriously jeopardized:
1. the emergence of antibiotic resistance with the spread of bacteria resistant to several antibiotics;
2. the decline in discovery and development of novel antibiotic compounds by industrial companies.

Resistance to antibiotics is a natural phenomenon originating in the exposure of bacteria to antibiotics. Like all living beings, bacteria are subject to the Darwinian rules of natural selection. When antibiotics are introduced in a medium, they exert a selective pressure on the bacteria: only the naturally resistant bacteria of the medium can survive. Random genetic mutations conferring resistance regularly occur spontaneously in several bacteria, but bacteria harbouring resistance-genes normally remain outnumbered by non-resistant bacteria. However, antibiotics, by killing non-resistant bacteria, offer the opportunity to resistant ones to multiply and become predominant. The selection of antibiotic-resistant bacteria during antibiotic treatments is therefore mechanical and hardly avoidable. The more we use antibiotic to treat infections, the more antibiotic resistance is bound to occur.

Discover how bacterial resistance happens.

The level of resistance in many bacterial species varies across geographic regions, but has clearly increased over the past decade:
• In the EU, there are about to 25,000 deaths related to antibiotic resistance.
• Each year in the US, about 2 million people get infected by bacteria resistant to antibiotics, leading to 23,000 deaths.

On the other side, the development of antibiotics has been increasingly challenging for the past two decades. Rising challenges in research, regulatory toughening, and lower returns on investments due to low prices have discouraged many pharmaceutical companies that were active in the field. Additionally, the fast development of resistance also contributes to the reduced attractiveness of antibacterial R&D. Since the use of new antibacterial products is, if not abandoned after a few years because of resistance, strictly restricted to limit the emergence of resistance, R&D investments can hardly be recouped for pharmaceutical companies. Thus, while in the meantime antibiotic resistance is on the rise, the number of novel antibiotics developed by the pharmaceutical industry has dramatically decreased for the past twenty years. No new families of antibiotics have been uncovered, and fewer major pharmaceutical companies are engaged in active antibacterial research.

If nothing is done to stop this trend, the economic burden of antibiotic resistance could be extremely heavy

Several studies show that resistant infections are expensive with increased healthcare costs and heavier burdens for families and societies. When infections become resistant to first-line medicines, more expensive therapies must be used: this is particularly problematic in developing countries where such expensive medicines may not be available. The longer duration of illness and treatment increases health-care costs and the financial burden to families and societies.

In the EU, the economic burden associated with antibiotic resistant infections weighs heavily on the individual, the health care system and society. Infections due to a sub-set of resistant bacteria are estimated to result in approximately 2.5 million extra hospital days per year and the overall societal costs are estimated to about 1.5 billion € per year. In the US, the direct cost of antibiotic resistance represents $20billon and an additional productivity loss of $35 billion.

Growing resistance with no action is feared to lead to 10 million people dying every year by 2050 and a reduction of 2% to 3.5% in Gross Domestic Product (GDP), costing the world up to $100 trillion.

Antimicrobial Resistance: a Global Environmental Threat

Antibiotics, widely used in human and veterinary medicines, are emerging environmental contaminants. In recent years, their growing presence in the environment has been of concern since antibiotics residues have been found in surface water, ground water, and even drinking water according to some studies. Antibiotics reach waters from various sources, such as wastewater from urban areas, industrial installations or agriculture-related facilities such as animal husbandries. If conventional treatment technologies are very efficient on a large number of compounds, some chemicals are persistent and are not removed by treatment facilities.The effort needed to reduce the antibiotic footprint will need to be of the same scale as that needed to tackle climate change.

Davolterra's committment within the BEAM Alliance

Da Volterra is part of the BEAM Alliance (Biopharmaceutical companies from Europe innovating in Anti-Microbial resistance research), an alliance regrouping 43 young innovative companies, from 12 European countries, who are committed to tackling antimicrobial resistance. The BEAM Alliance works toward the improvement of regulatory, investment, and commercial environments in Europe for research, development, approval and market viability of new products combating antimicrobial resistance.
Learn more on the BEAM Alliance and its latest position paper.