The Fight Against Resistance: Shorter is Better


Brad Spellberg, MD, highlights research that indicate shorter courses of therapy are safer and as effective as longer ones, as well as the importance of randomized controlled trials.

Over 10 years ago, Louis Rice, MD, delivered the Maxwell Findland Lecture at IDWeek 2007 discussing the threat of antibiotic resistance and the importance of advocating for rational antibiotic administration.

“The simplest approach is to use fewer antibiotics and thereby apply less selective pressure to the prevalent flora,” Dr. Rice said in his lecture which was later published in Clinical Infectious Diseases. “Among available strategies to reduce use, reductions in length of antimicrobial regimens are the safest and are likely to be the most palatable to practicing clinicians. Studies are urgently needed to define minimal lengths of therapy to ensure that efforts at reduced use are safe and effective.”

Although the focus on using shorter courses of therapy is no longer a new concept, it still has not yet reached wide-spread practice.

In an editorial published in the Journal of Hospital Medicine earlier this year, Brad Spellberg, MD, of the Los Angeles County-University of Southern California Medical Center discussed his mantra “shorter is better,” when it comes to courses of antibiotic therapy, and aspects he feels are critical to changing the prescribing attitudes of physicians to confront antibiotic resistance head-on.

Dr. Spellberg introduces the concept of prescribing based on Constantine-Units in his editorial. In 321 AD, Constantine the Great adopted the 7-day week; thus 1 Constantine Unit is equal to a 7-day course of antibiotics. As it stands, the standard has become 7 to 14 days of antibiotics. As a result, providers continue to provide long durations of antibiotic therapy, which drive resistance.

Although it is not yet possible to tailor durations of therapy to each individual patient, Dr. Spellberg advocates that prescribers should focus on reducing the risk of adverse events and of driving resistance instead of maximizing cures across a population which can result in overtreating infections. He reflects that the persistence of symptoms does not necessarily indicate bacteria are still present; rather, symptoms can persist even after the bacteria are dead and can result from inflammatory response of the bacteria. By continuing a duration of antibiotics, the infection is being over treated.

Since Dr. Rice’s address, there have been dozens of trials comparing short courses of antibiotics with longer durations for a variety of different acute bacterial infections. In a study published in the Society of Hospital Medicine, investigators conducted a systematic review comparing the outcomes of shorter and longer antibiotic courses among hospitalized adults and adolescents.

Across 13 studies which evaluated 1727 patients, the investigators observed no significant difference in clinical efficacy (d = 1.6% [95% CI, -1.0%-4.2%]). The authors concluded that based on the available literature, shorter courses of antibiotics can be used safely in hospitalized patients with infections such as pneumonia, urinary tract infections, and intra-abdominal infections while achieving clinical and microbial resolution.

“In the last 25 years, there have been by my count 45 randomized trials comparing short-course therapy to traditional courses of therapy, across a variety of types of serious infections,” Dr. Spellberg said in an interview with Contagion®. “In every one of those studies, shorter therapies were equally effective to longer [ones] and in many of the studies, there were fewer side effects from the shorter therapies. [Furthermore,] in some studies, when they looked, [they found] less emergence of resistance in the shorter therapy.”

Although some randomized trials are providing real-world evidence that shorter courses of antibiotic can be effective, there is still work to be done to encourage providers to implement these findings into their prescribing practices.

Dr. Spellberg emphasized that there is a need for more publicly reported data and for national guidelines to be modified to be aligned with the data from these randomized controlled trials.

“The bottom line is when we’ve looked, in most cases (with a few exceptions) shorter than traditional courses of antibiotic therapies have been equally effective, safer, and reduced the emergence of resistance. That’s why I say shorter is better,” Dr. Spellberg concluded.

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