Chapter 1: The Antibiotic Revolution

In the early 1900s, the average life expectancy in the United States was just 47 years; by 2017, this figure soared to 78.6 years. A key factor in this remarkable increase has been the advent of antibiotics. However, the question looms: what if antibiotics cease to be effective?

The misuse and overprescription of antibiotics have led to a significant number of pathogenic bacteria developing resistance. The Centers for Disease Control and Prevention (CDC) has identified 18 drug-resistant microbes as urgent or concerning threats.

> “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.” — Sir Alexander Fleming

To mitigate the emergence of drug resistance, healthcare professionals are advised to prescribe antibiotics judiciously. Yet, the challenge remains: how do we address the bacteria that are already resistant? The need for new antibiotics is urgent, but the unappealing business model surrounding antibiotic development has deterred major pharmaceutical companies from investing in this area.

Antibiotics are expensive to develop, and many of the straightforward targets have already been exploited. Additionally, reduced prescribing practices diminish the potential market for these drugs. Insurers and healthcare providers often hesitate to reimburse new antibiotics at their market prices, exacerbating the situation.

Consequently, many companies find themselves targeting bacterial strains that affect a limited number of patients. For instance, Achaogen developed Plazomicin, a novel antibiotic aimed at carbapenem-resistant Enterobacteriaceae—a severe infection that only a small fraction of the U.S. population contracts. Unfortunately, the drug did not perform well commercially, leading Achaogen to file for bankruptcy. Other antibiotic firms, such as Melinta and Tetraphase, have also seen their market values plummet, with Melinta recently acquiring Tetraphase.

Chapter 2: Rethinking Antibiotic Development

To foster the development of new antibiotics, companies must find ways to mitigate the high costs associated with their creation. Adopting a platform approach can help reduce these expenses over time. This method allows a company to utilize the same underlying technology while modifying specific components to develop new drugs.

Innovative, selective antibiotics that do not contribute to drug resistance can encourage higher prescription rates. Below, I spotlight two startups making strides in novel antibiotic therapies: