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The rise of drug-resistant “Superbugs” has been a public health concern for many years. However, new information from the Centers for Disease Control and Prevention (CDC) indicates that the problem continues to accelerate. Clinicians are reporting emerging virulent pathogens that are resistant to currently available treatments, including antibiotics reserved as last lines of defense. The time to aggressively attack this problem is now, through a coordinated effort by public and private organizations including public health agencies, industry, academia, healthcare facilities and other key parties.

In September 2016, a Nevada woman died in an acute care hospital in Reno from septic shock. The cause: complications from an incurable infection caused by a carbapenem-resistant strain of enterobacteriaceae (CRE). Testing showed that this superbug - specifically, a multi-drug resistant (MDR) strain of the bacterium Klebsiella pneumoniae - had spread throughout her body and was resistant to 26 different antibiotics. Unfortunately, this is not an isolated incident and the frequency of CRE and other MDR bacterial infections continues unabated.

Jeffrey Stein, Ph.D.
President and CEO of Cidara Therapeutics, Chairman of Antimicrobials Working Group

Fungal infections have received considerably less public attention than bacterial infections, yet there are an estimated 97,000 fungal-related deaths in the U.S. annually. The fungi Candida is a common cause of hospital-acquired bloodstream infections, with often deadly consequences: 35 percent of patients infected die within 12 weeks of diagnosis, according to a 2009 study published in Clinical Infectious Disease. To make matters worse, a new Candida strain, known as C. auris, emerged in November 2016. This virulent strain recently infected 13 patients, four of whom subsequently succumbed to the infection. In some of these cases, C. auris proved to be resistant to all three classes of drugs (polyenes, azoles and echinocandins) available to treat fungal infections. This new strain is particularly concerning in light of the fact that the last new class of antifungals was introduced in 2001 and no new antifungal agents have been approved for Candida bloodstream infection since 2007.

In the U.S. alone, the CDC estimates an annual death toll of 23,000 from drug-resistant infections, with related healthcare costs of approximately $20 to $25 billion. Both bacterial and fungal infections are now resistant to many of the drugs available to treat them.

This antimicrobial resistance (AMR) is closely linked to the overuse of cheap, generic antibiotic and antifungal drugs. Core strategies to combat the problem include education about appropriate prescribing of antimicrobials, improved diagnostic capabilities, and initiatives to speed the development and approval of new antimicrobial drugs. The CDC reports, for example, that widespread usage of antifungals in the azole class in particular has stimulated an increase in azole-resistant strains of Candida.

There’s been some progress, however, starting with greater high-level awareness about AMR threats to public health. In September 2016, the United Nations General Assembly held a meeting at its New York headquarters focusing on AMR. This was only the fourth time in the history of the UN that a meeting had been convened to discuss a health issue. World leaders at the meeting signed a declaration pledging their commitment to take concrete action to tackle AMR, including providing resources for research into new drugs, vaccines and diagnostics, and ensuring good stewardship of antimicrobial use in both humans and animals.

A collaborative approach bringing together industry, government and researchers

More rapid drug development is a key element in the battle against AMRs. A historically challenging regulatory environment that necessitated large and costly clinical trials has been a barrier to the development of new anti-infectives. The 2012 Generating Antibiotic Incentives Now (GAIN) Act has partially addressed this challenge by providing fast-track FDA review and extended market exclusivity for qualified new antibiotics. While the GAIN Act has been broadly viewed as an encouraging first step, additional improvements to the regulatory and commercial environment for new anti-infectives will be needed to combat drug-resistant pathogens. The 21st Century Cures Act, passed last year, contains provisions for a new approval pathway for antibacterial and antifungal drugs that treat a serious infection in a “limited population of patients with unmet needs.” This is intended to provide a faster path to approval for new, life-saving drugs for patients with multi-drug resistant infections.

Spurring the pipeline for new antibiotics and antifungals also depends upon physician involvement in research studies, along with the help of committed organizations such as the Antimicrobials Working Group (AWG), an industry-led, 501(c)(6) nonprofit comprised of emerging antimicrobial companies. The organization aims to provide antimicrobial companies a collective voice in policy and regulatory solutions. AWG’s priorities include encouraging greater flexibility in regulatory approval requirements for new drug development, along with exploring alternative pricing and reimbursement models that will support a robust antimicrobials pipeline.

Superbugs are not a passing trend; unless swift and coordinated action takes place within and outside of the healthcare community, we can expect an ever-growing rise in preventable infections and deaths. Unlike many diseases such as cancer, however, we now have a solid understanding of both the cause and the cure for the problem of antimicrobial resistance.

Jeffrey Stein, PhD, is President and Chief Executive Officer of Cidara Therapeutics and Chairman of the Antimicrobials Working Group (AWG).

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