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Resistance to antibiotics

Resistance to antibiotics is emerging as one of the biggest healthcare challenges of the 21st century. It endangers the lives of an increasing number of patients and threatens many of the practices of modern medicine on which we have come to rely

Microbial resistance is an evolutionary process occurring in response to the use of anitbiotics. This natural evolutionary process is accelerated by overuse and misuse of antibiotics in humans and in animals, by poor infection control and often by inadequate sanitary conditions. Every country is affected1 and it is estimated that more than 700,000 people die each year as a result of microbial resistance

One of the greatest areas of unmet medical need is caused by the spread of emerging resistance mechanisms among Gram-negative bacteria. This emergence is both widespread and growing exponentially. Pathogens such as Klebsiella pneumoniae, a common intestinal bacteria, have accumulated multiple resistance mechanisms and can cause life-threatening infections, particularly in hospitalized patients. Other Gram-negative bacteria, including Pseudomonas aeruginosa are also of growing concern
Emerging resistance mechanisms expressed by Gram-negative bacteria result in these pathogens becoming non-susceptible to many classes of antibiotics, including antibiotics of last resort such as carbapenems The concern over microbial resistance is now so great that The World Health Organization, the US Centers for Disease Control, the European Commission and a number of national governments have made tackling this problem a priority for both policy and funding. They are focusing on the following key areas:

1.Reducing the overuse and misuse of antimi crobials, including antibiotics

2.Implementing robust prevention measures including improved cleanliness in hospitals

3.Improving surveillance and monitoring in humans and animals

4.Developing new effective treatments

Developing new classes of antibiotics that can tackle the issue of microbial resistance is a particular challenge. Over the last two decades, there have been few novel antibiotics approved by health authorities and of these a very small proportion can be identified as having a truly novel mechanism of action. Therefore, it has become increasingly important to explore ways to restore the effectiveness of antibacterial agents that were highly effective prior to the evolution of emerging resistance mechanisms. This approach is particularly appropriate for the class of β-lactam antibiotics. β-lactam antibiotics include penicillins, cephalosporins and
carbapenems, which have been a mainstay of antibacterial treatment for many years, saving countless lives and transforming the practice of modern medicine. However,due to their widespread use and subsequent emergence of specific resistance mechanisms, β-lactam antibiotics are becoming much less effective against many important pathogens. Successful strategies that restore the effectiveness of β-lactam antibiotics include the co-administration of a β-lactamase inhibitor (BLI) together with an antibiotic. BLIs are compounds that inhibit the action of β-lactamases, the enzymes produced by some bacteria that make them resistant to certain antibiotics. Allecra is developing an extended spectrum BLI that restores the effectiveness of cefepime, a powerful antibiotic, even in the face of some potent, emerging, β-lactamase mediated resistance mechanisms. Allecra’s extended spectrum BLI is known as Enmetazobactam and it is currently in Phase 3 clinical trials
1. World Health Organization Factsheet 194. Available at www.who.int/mediacentre/factsheets/fs194/en. 2. Review on Antimicrobial Resistance. www.amr-review.org.

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