August 22, 2017
A provocative analysis in The BMJ (26 July 2017) 1 questioned the dictum: “complete the course of antibiotics to prevent drug resistance.” In addition to sparking controversy among health professionals, the message sowed confusion in the media and the public at large. The team of researchers argue that there is no evidence indicating that stopping antibiotics early will put a patient at increased risk of drug-resistant infections and that completing the course may in fact fuel antibiotic resistance rates, while providing no more benefit to the already-cured patient. They also pointed out that the danger of long courses of antibiotics has more to do with fostering resistance in non-target bacteria—that is, not the ones causing the infection being treated, but the multitudes in the gut and elsewhere, which can pass on resistance genes to all manner of related and unrelated bacteria.
Clinical trials have established the efficacy of antibiotics at curing infections and saving lives. However, the trials have not always been focused on determining how many days and doses of antibiotics should be given for a particular infection. It’s complicated, because the same type of bacteria—e.g., Staphylococcus aureus—can infect many different sites, and the optimal. regimen may be different for all of them. In fact, there are very few infections for which treatment durations have been well defined by clinical trials. The default has been possibly longer than necessary antibiotic courses to make sure the infection is cured. But that calculus continues to change as the link between antibiotic use and antibiotic resistance has become clearer, coupled with the recognition that the pipeline of new antibiotics is woefully thin. That is the rationale behind the new analysis: pare back antibiotic courses to the minimum.
It is true that there is no evidence to indicate that stopping antibiotics early will lead drug resistant infections. However, it is important to remember that the primary reason for giving antibiotics is to cure infection, not to prevent drug resistance. While we may need to change prescribing habits, the only way that can be done responsibly is to systematically assess regimen lengths for common infections in clinical trials. We believe the BMJ authors have jumped the gun to suggest that we know enough to shorten regimens immediately. What’s worse—though not the authors’ message—is that many media sources implied that patients themselves should decide when to stop their antibiotics.
This is not the first time that antibiotic duration has been questioned by medical researchers, or that a plan for prioritized clinical trials has been developed. 2 A proposal to study the duration of antibiotics for common infections was made prominently a decade ago to the U.S. National Institutes of Health, but there was little follow-through. 2 However, a few trials have been completed, and their results only strengthen the case for doing more. Consider the example of ear infections in young children. The standard practice is to give antibiotics for 10 days. A recent clinical trial tried stopping antibiotics after 5 days, and found it less effective than the standard 10 days. They also observed no difference in drug resistance among harmless bacteria residing in the throat. In this case, the currently recommended longer regimen is better.3 Another example is kidney infections, for which the standard course is 14 days of antibiotics. However, a recent clinical trial indicated that 7 days of antibiotics is as effective as 14.4So, the answers are likely to be varied and unpredictable without solid evidence.
We need to get serious about generating the evidence needed to rationalize antibiotic courses—keeping the patient first, but being good antibiotic stewards, as well. We would rather not read the same headline a decade from now.
Sumanth Gandra, MD, is a Resident Scholar at CDDEP.
Image via oliver.dodd (CC BY 2.0)
1. Llewelyn MJ, Fitzpatrick JM, Darwin E, Tonkin-Crine S, Gorton C, Paul J, Peto TE, Yardley L, Hopkins S, Walker AS. The antibiotic course has had its day. BMJ. 2017 Jul 26;358:j3418.
2. Rice LB. The Maxwell Finland Lecture: for the duration—rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile. Clinical infectious diseases. 2008 Feb 15;46(4):491-6.
3. Li B. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. Journal of Emergency Medicine. 2017;3(52):391-2.
4. Sandberg T, Skoog G, Hermansson AB, Kahlmeter G, Kuylenstierna N, Lannergård A, Otto G, Settergren B, Ekman GS. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. The Lancet. 2012 Aug 10;380(9840):484-90.