About Antibiotics: Complete the Course, or Stop When You Feel Better?

All medical professionals have likely dealt with the aftermath of the media’s picking up a provocative article or concept and popularizing it, often with an unintended change in the original message. Usually I cringe when I hear these, knowing that I will be facing questions about the mixed message that was sent. After all, how many times have we almost cured cancer? However, this time, I was happy to see a focus on the undetermined importance of fixed antibiotic durations, commonly presented under the guise of “maybe you can stop antibiotics when you feel better” or something similar.

This wave of consumer stories was stimulated by an interesting hybrid review/commentary written in the BMJ at the end of July 2017 by Llewelyn and colleagues.¹ Titled “The Antibiotic Course Has Had Its Day,” the article challenged the notion that completing antibiotic courses after symptom resolution has any benefit. The authors were right to do so. The notion of fixed-duration antibiotic courses is not supported in the literature, something that can probably be discerned by the relationships between antibiotic durations and numbers of convenience. Even more intriguing is the lack of an evidence base for the most common reasons cited for the mantra to “take all your medicine even if you feel better.” Two common rationales for this exist.

The first is that treatment failure is more likely with shorter courses of antibiotics. Although this is true for some chronic infections like tuberculosis, repeated studies of various acute bacterial infections generally show that shorter courses are as effective as more traditional courses of therapy. This has been shown with hospital-acquired and community-acquired pneumonia (CAP), pyelonephritis, pharyngitis, skin and skin structure infections, and intra-abdominal infections.¹ Notably, a recent study of otitis media in young children showed higher failure with a short course, though this is a singular study in a non-severe infection.² Most interesting to me is a study of CAP that compared treatment using daptomycin (which is inactivated by pulmonary surfactant) with ceftriaxone.³ The study found the drugs to be equivalent if patients in the daptomycin group received <24 hours of antibiotics (such as 1 dose of levofloxacin or ceftriaxone) before they were randomized. Because patients taking daptomycin essentially received placebo after they were randomized, the length of time we need to treat patients with CAP needs to be further investigated.

The second rationale given for taking a full course of antibiotics is that it prevents resistance from emerging after therapy. This feels intuitive to many people—that completing a full course of antibiotic prevents any “leftover” bacteria from becoming resistant, living on to cause an infection from a now harder-to-treat pathogen. However, there is no evidence to support it. Bacterial resistance to antibiotics emerging de novo during therapy is a relatively rare occurrence that requires genetic mutations that lead to resistance, all while the bacteria are being affected by antibiotic therapy. Most mutations do not lead to resistance, and many of them have negative effects on the bacteria. It takes a bit of luck to create a resistance mechanism against an antibiotic through random mutation.

The belief that prolonging antibiotic durations prevents resistance is probably due to a misunderstanding of the effects of antibiotics. With rare exceptions, antibiotics broadly affect bacteria, and each dose prolongs exposure to antibiotics for many species in the human microbiota, not just for a particular pathogenic organism leading to infection.⁴ This exposure selects for resistant pathogens that colonize patients, and prolonging that exposure increases the likelihood that their dominance will increase. Once antibiotic therapy has selected for resistant organisms, they can exchange genes with susceptible pathogens to further spread antibiotic resistance to new species. We have to remember that antibiotics always affect the ecosystem of the human microbiota and that there are no true targeted antibiotics.

A final reason for prescribing antibiotic courses is psychological. It is known that prescribers are more comfortable overprescribing antibiotics for patients for infections than taking a risk of undertreating them, which removes the burden of understanding when to stop antibiotics from the patient.⁵ Addressing this is a matter of education, a notion that is problematic when current authorities preach “take all your antibiotics as prescribed.” I hope further studies will solidify the roles of symptom-guided and shorter-course antibiotic regimens. Furthermore, careful education by health care professionals, to patients about appropriate use of antibiotics, will ultimately help all of us as we work to preserve the societal benefits that these important medical resources afford.

Jason C. Gallagher, PharmD, FCCP, FIDSA, BCPS, is a clinical professor at Temple University School of Pharmacy and a clinical pharmacy specialist in infectious diseases at Temple University Hospital, both in Philadelphia. He is also the director of the PGY2 Residency in Infectious Diseases Pharmacy at Temple. He is an active member of SIDP.

References

1. Llewelyn MJ, Fitzpatrick JM, Darwin E, SarahTonkin-Crine, Gorton C, Paul J, et al. The antibiotic course has had its day. BMJ. 2017;358:j3418. doi: 10.1136/bmj.j3418.
2. Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, et al. Shortened antimicrobial treatment for acute otitis media in young children. N Engl J Med. 2016;375(25):2446—2456. doi: 10.1056/NEJMoa1606043.
3. Pertel PE, Bernardo P, Fogarty C, Matthews P, Northland R, Benvenuto M, et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis. 2008;46(8):1142—1151. doi: 10.1086/533441.
4. Willing BP, Russell SL, Finlay BB. Shifting the balance: antibiotic effects on host—microbiota mutualism. Nat Rev Microbiol. 2011;9(4):233—243. doi: 10.1038/nrmicro2536.
5. Teixeira Rodrigues A, Roque F, Falcão A, Figueiras A, Herdeiro MT. Understanding physician antibiotic prescribing behaviour: a systematic review of qualitative studies. Int J Antimicrob Agents. 2013;41(3):203—212. doi: 10.1016/j.ijantimicag.2012.09.003.