Antibiotics: Preserve the miracle?

The placebo effect is well-known in modern medicine. Unfortunately, the most effective medicines we’ve ever discovered are more often used as placebos rather than cures. What are these medicines? Antibiotics.

They’ve added 20 years to the average human life expectancy, some would call this a “miracle”. In-fact “preserve the miracle” is the official slogan for Antibiotic Awareness Week. But it’s a word that carries some baggage, after all miracles don’t come with adverse consequences.

Antibiotics, like other medicines have side-effects. In the patient these can range from allergies and Stevens-Johnson syndrome (beta-lactams and doxycycline), through to anaphylaxis and long-QT syndrome (macrolides and fluoroquinolones). However, antibiotics have consequences that extend beyond the human host. Antibiotics are bacterial weapons of mass destruction, indiscriminately killing friend and foe alike.

The microbiota acts as an extension of its human host, mediating immunological modulation, metabolic functions and even production of serotonin. Loss of these organisms caused by antibiotic use creates another set of complications for the host including metabolic disorders (i.e. weight gain) and auto-immune diseases. The microbiota also provides other benefits to the host. By growing in the internal and external ecosystems we provide to these bacteria, they prevent potentially harmful microbes doing the same. By diminishing our microbiota with antibiotic use we leave ourselves open to infections, particularly those caused by resistant bacteria.

Evolution (depending on geography), is not a controversial concept. Changes in the environment select and in some cases act as drivers for genetic modification. Genetic modifications which enable better survival (increased fitness) persist, whilst those that decrease survival (reduced fitness) are outcompeted. This allows organisms to become better adapted to their environment, and the process begins again. We are now in the “Anthropocene” era, where humans have become the dominant selection pressure acting upon organisms. Antibiotic contamination of our internal and external ecologies (including environmental waters) is just one of the many examples of how we act as a selection pressure. Once-treatable bacteria are now resistant to every antibiotic we have in the therapeutic armamentum. Resistant infections now claim around 50,000 lives per year in the US and Europe, and outnumber motor vehicle accidents as a cause of death.

Why are antibiotics so important? Because most medical interventions compromise host defences. Intubation acts as a portal for microbes to otherwise protected sites. Surgery temporarily compromises the impermeable barrier for microbes. Chemotherapy and several other treatments are immunosuppressive, increasing the hosts’ likelihood of developing infections. These vulnerable patients require antibiotics to survive. We need these antibiotics to keep these medical interventions viable. The fight against antimicrobial resistance has become the battle to keep modern medicine alive.

Modern medicine’s centerpiece is the tertiary hospital, which is a testament to our ability to extend life. It’s also the place where the most vulnerable patients cluster. In this setting, high risk patients are in close proximity to one another. These patients rely on medicines selecting for resistant organisms. Both these factors increase the chances of outbreaks caused by resistant organisms, and makes the hospital a dangerous environment.

Hospital “outbreaks” involving the most resistant organisms claim ≥ 50% of infected patients. As these organisms become more common, life-extending procedures can no longer be safely performed. The situation in Europe is becoming increasingly dire and contingency plans are being made. These plans include halting elective surgery and other procedures deemed to be too high risk.

Antibiotics are therefore far from miracles and more akin to Faustian bargains. The more power we seek to wield using them, the greater the cost to human health and future potency of these medicines. But what can be done?

We can control the level of antibiotic use in hospitals. In fact, the emergency department has great influence over antibiotic use in most hospitals. Around 60% of antibiotics used in the hospital are started in the emergency department. These empirical antibiotic treatments are often not reviewed following administration in the emergency department, contributing to on-ward use.

Antibiotic resistance is a major issue that threatens all of us, from patients to practitioners. We’re all in this together, pointing the finger is no longer productive. We all want the same outcomes: to protect the health of our immediate patients, to protect the health of future patients and to ensure modern medicine has a sustainable future. To this end, it’s time we began a dialogue to achieve meaningful change.

References

• Antimicrobial resistance (WHO)
• Gillings, M. R. & Stokes, H. W. (2012). Are humans increasing bacterial evolvability? Trends in Ecology & Evolution 27, 346–352. (Reference)