By Katharine Sedivy-Haley, PhD Candidate, Hancock Lab, CBR

Doctors and healthcare professionals have long urged patients to always finish a course of antibiotics to prevent the development of antibiotic resistance. However, a recent article by Martin J Llewelyn and colleagues in the BMJ¹ sparked controversy by suggesting that taking the full course is not only largely unnecessary, but actually increases the risk of antibiotic resistance.

According to Llewelyn et al., pioneers of antibiotic treatment were concerned with eliminating the infection and avoiding resistance in the targeted pathogen, a problem researchers observed in lab cultures when insufficient antibiotic was used. Antibiotic resistance also developed clinically in tuberculosis patients treated with only a single antibiotic rather than a combination. Doctors accordingly adopted a “better safe than sorry” policy: a longer duration of treatment might be necessary to prevent relapses or resistance, and extra antibiotics couldn’t hurt.

However, researchers have since discovered that over-use of antibiotics can have negative effects, including changes in the patient’s native microbial flora. These changes include the development of resistance genes in bacterial species such as Escherichia coli or Staphylococcus aureus – normally harmless organisms that can opportunistically cause disease if, for example, the host’s immune system becomes weakened or if the bacteria are allowed to access areas of the body that typically are free from bacteria. Resistance genes can also transfer “horizontally” from harmless to pathogenic species. The risk of this collateral resistance developing due to longer-than-necessary antibiotic courses may outweigh the risk of resistance in the targeted pathogen.

While in some cases long courses are clinically necessary, for most pathogens there is little evidence supporting current duration of treatment. Llewelyn et al. summarize seven controlled studies investigating specific infections. Of these, six found shorter courses equally effective to the standard course. Three of these trials assessed antibiotic resistance; two found a lower risk from the shorter course while the final trial did not observe a difference in resistance. For some infections, treatment may be ended once symptoms resolve, as seen in one study of community acquired pneumonia. Unfortunately, comprehensive research into shortening treatment has been impeded by the widespread belief that this will cause antibiotic resistance. Therefore, Llewelyn et al. call not only for clinical optimization of the duration of antibiotic treatment, but also for public education initiatives renouncing previous recommendations to “complete the course.”

Responses to the article have been mixed. Many agree that there is insufficient evidence supporting longer antibiotic courses for many pathogens, but do not believe that the evidence supports a general preference for shorter courses or for withdrawing antibiotics when the symptoms resolve. In particular, patients with vulnerable immune systems require longer treatment. These critics support the article’s call for more research into treatment duration, but reject the need to immediately reverse existing recommendations. A second concern involves the article’s effect on the public: if patients are encouraged to ignore medical advice regarding length of treatment they may also ignore other dosage instructions, or fail to properly dispose of unused antibiotics. This could cause antibiotic resistance – and in the former case failed treatment – independent of length of treatment. Certainly some of the media coverage has been sensationalized and potentially misleading, discussing the article’s questions as if they were conclusions, or writing as if Llewelyn et al. were directly advising the public instead of indirectly communicating through educators and doctors.

Llewelyn et al. do not advise patients to disregard their physicians; rather, they seem merely to want the public to know that the issue is not settled. For now, patients can to talk to their doctor about whether an antibiotic is necessary and whether a shorter course of treatment is possible – and be ready for changing recommendations as new evidence comes in.

1. Llewelyn, M. J., Fitzpatrick, J. M., Darwin, E., Gorton, C., Paul, J., Peto, T. E., … & Walker, A. S. (2017). The antibiotic course has had its day. Bmj, 358, j3418.