Has antibiotic course come to an end?

With little evidence that failing to complete a prescribed antibiotic course contributes to antibiotic resistance, it is time for policy makers, educators, and doctors to drop this message, argues Martin Llewelyn, professor of infectious diseases at Brighton and Sussex Medical School.

Antibiotics are crucial to modern medicine but antibiotic resistance is a global, urgent threat to human health.

Historically, antibiotic courses were driven by fear of undertreatment, with less concern about overuse. Public communication about antibiotics often emphasizes that patients who fail to complete prescribed antibiotic courses put themselves and others at risk of antibiotic resistance.

“Always complete the full prescription, even if you feel better, because stopping treatment early promotes the growth of drug-resistant bacteria,” suggested WHO, in 2016.

Infections typically begin when a small population of microorganisms gain access to the host and replicate. Target selected resistance can occur with inadequate antimicrobial dosing or with monotherapy for infections for which spontaneous resistant mutations arise on treatment, such as tuberculosis.

However, most of the bacterial species now posing the greatest problems do not develop resistance through target selection. The clinical threat comes mainly from species such as Escherichia coli and the so called ESKAPE organisms, which are all found harmlessly in us, on us, or in our environment.

When a patient takes antibiotics for any reason, antibiotic sensitive species and strains present among commensal flora on their skin or gut or in the environment are replaced by resistant species and strains ready to cause infection in the future.

Antibiotics are conventionally prescribed for recommended durations or courses. Contrary to popular belief, little evidence exists that currently recommended durations are minimums, below which patients will be at increased risk of treatment failure.

For many indications, recommended durations have decreased as evidence of similar clinical outcomes with shorter courses has been generated.

Shorter duration of treatment has been shown to reduce clinical efficacy in a few cases such as otitis media. Even in this situation though, differences relate to prolongation of symptoms not treatment failure, disease recurrence, or selection for resistant pathogens.

The key argument for changing how we discuss antibiotic courses with patients is that shorter treatment is clearly better for individual patients. Not only does a patient’s risk of resistant infection depend on their previous antibiotic exposure but reducing that exposure by shorter treatment is associated with reduced risk of resistant infection and better clinical outcome.

The fallacious belief that antibiotic courses should always be completed to minimize resistance is likely to be an important barrier to reducing unnecessary antibiotic use in clinical practice and to developing evidence to guide optimal antibiotic use.

In primary care, strategies have been developed to avoid unnecessary antibiotic courses being started—for example, through enhanced communication training, point-of-care tests, and use of delayed prescriptions.

Owing to its simple and unambiguous nature, the “complete the course” message has persisted despite not being supported by evidence and previous arguments that it should be replaced. Nevertheless, there is evidence that, in many situations, stopping antibiotics sooner is a safe and effective way to reduce antibiotic overuse.

Public education about antibiotics should highlight the fact that antibiotic resistance is primarily the result of antibiotic overuse and is not prevented by completing a course. The public should be encouraged to recognize that antibiotics are a precious and finite natural resource that should be conserved.