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Antibacterial resistance: is there a way out of the woods?

n antimicrobial resistance n ESKAPE pathogens n multidrug-resistant bacteria Most people in the second half of the 20th century – clinicians and scientists included – would have believed that bacterial infections would be eradicated, or at least easily managed, by the start of the new millennium. Certainly the promise made by the discovery of antibiotics in the 1940s was fulfilled, resulting in millions of lives saved and astonishing medical advances that would have been otherwise impossible. However, in the USA there are close to 2 million hospital-acquired infections and nearly 99,000 deaths yearly, costing US$20–30 billion, with resistant bacteria being the main culprits [1]. Infections due to these organisms result in longer courses of therapy, increased hospital stays and higher mortality rates than those due to susceptible pathogens. These resistant bacteria are also spreading into the community and affecting healthy people, sometimes with dire consequences; as antibiotic resistance increases so too will these numbers, which are already to high. Yet against this backdrop only two new anti biotics were approved in the last 4 years. We are now facing a crisis that threatens to reverse decades of medical progress and will take clear planning, careful guidance and worldwide cooperation to avert [1]. The unfortunate coincidence of a number of factors that individually would have been significant, in combination could negate the benefits afforded by antibiotics over the last 70 years and lead to increasing numbers of infections caused by multidrugand pan-resistant organisms. In truth, bacteria resistant to antibacterial drugs will emerge as soon as the two are introduced; if the organism’s fitness is not compromised by the resistance determinant, it will have a selective advantage when the antibiotic is present. Conversely, bacteria carrying burdensome resistance determinants can often overcome a fitness cost with compensatory mutations. However, although antibiotic resistance has always been simmering, significant investment in antibacterial research has managed to keep it from boiling over through the steady development of new agents. That is no longer the case as more and more large pharmaceutical companies are exiting the field, due to economic as well as regulatory issues unique to antibacterial drug discovery and development. The Infectious Diseases Society of America (IDSA) has taken on this challenge and issued a set of proposals aimed at increasing awareness and reversing the course of rising antibiotic resistance [1]. The collateral effects of reduced antibiotic efficacy may not be obvious, but they are far-reaching, encompassing procedures such as routine surgery, chemotherapy, intensive care unit therapies, mechanical ventilation, HIV patient care, organ transplant, neonatal/premature infant care, care of the elderly, including residents of long-term care facilities, care of immunocompromised patients and invasive surgical measures – all of which would be impossible without the availability of reliable antibiotics. Even with antibiotics, infectious diseases are the second and third leading causes of death worldwide and in the USA, respectively [2]. To not heed the IDSA’s call could result in significant increases in mortality due to infections and a concomitant decrease in life span for the populations of even the wealthiest countries.