“These have been enshrined in our guidelines, and they are the tradition that we are trying to battle now with stewardship in arguing for shorter and less antibiotic therapy,” said Spivak, co-director of the antimicrobial stewardship programs at University of Utah Health and the Salt Lake City Veterans Affairs Healthcare System.
“Antibiotic practices have been maintained over years, often due to a long absence of new data suggesting that there was an alternative approach,” she said. “Fortunately, that is changing now, [but there remains] historical inertia. Many of us were told, ‘Well, this is the way I was taught to do this, and so this is how I’ve done it.’ Then personally, these dogmas get reinforced by our own practice and our own experience.”
Spivak is a member and the 2022 chair of the antimicrobial stewardship committee for the Infectious Diseases Society of America (IDSA).
“Unfortunately, our guidelines have really, in sort of a very official way, enshrined these dogmas in writing with strong recommendations,” she said. “Often [there is a] lack of quality of evidence behind them, but when that becomes the standard of practice, people are really afraid to contradict our IDSA guidelines. And that, of course, is a huge barrier to change.”
Strong Recommendation, Weak Evidence
Spivak cites a study of the IDSA guidelines that shows strong recommendations too often are supported by weak evidence.1
“This [shows that] 75% of recommendations for treatment in IDSA guidelines carry a strong recommendation, but only roughly 8% of those have any high-quality evidence behind them,” she told SHEA attendees. “We’re very confident in our decisions, but we also say that most of that is based on low and very low-quality evidence.”
The historical thinking has been the more disease, the more drugs needed, she noted.
“If you have a really serious disease, you probably need multiple antibiotics, or you might need them for longer durations, because again, it’s bigger disease, bigger drugs, and the fallacy that antibiotics are not toxic.”
Although antibiotics have “selective toxicity” to the targeted pathogen, they also can cause side effects, allergic reactions, and set up the onset of Clostridium difficile infection by altering the gut microbiome. Thus, the growing movement for shorter courses of therapy and the use of oral medicine instead of intravenous lines that deliver drugs at the risk of bloodstream infections.
“We are hostage to history, but shorter duration of antibiotic therapy is better,” Spivak said. “That should really be the take-home [message] for everybody: Shorter is better.”
How long has this been going on? A 10-day recommendation for antibiotic therapy for group A strep pharyngitis was “arbitrarily” assigned in a 1950 paper.2 Moreover, the 10-day antibiotic treatment duration was subsequently set for other infections, such as pneumonia.3
“I think UTIs (urinary tract infections) are a great example of how we are hostage to history,” she said. “If we track UTI diagnosis and treatment recommendations going back to the 1950s, a UTI was defined by the presence of bacteria or bacteriuria in the urine. And the goal then was to cure and eradicate and get rid of bacteria in the urine. Therapy here was defined as negative culture results for an extended period of time.”
Even into the 1970s, the extended duration of antibiotic therapy was recommended even for asymptomatic bacteriuria, which generally is not considered a UTI today.
“Again, UTI was diagnosed by bacteria in the urine. The goal, of course, was to eliminate that,” Spivak said. The recommended duration was prolonged, she added, citing a paper that stated “about two weeks to several months might actually be ideal.”4
Eventually, clinicians recognized that bacteriuria was common, regardless of how long the antibiotic duration.
“There was also recognition that subsequent infections were very rare regardless of whether or not you eradicated bacteriuria or the duration of antibiotics,” she said. “Now we have healthier recognition of what asymptomatic bacteriuria is — that it doesn’t need to be treated. There are downsides and potential harms to over-treating asymptomatic bacteriuria. Our goal is, really, clinical response, not microbiologic response, and follow-up urine cultures are no longer recommended.”
Indeed, there is accumulating evidence that shorter duration of antibiotic therapy is just as effective as longer administration. For example, one study found that three days of treatment was just as effective as an eight-day course of therapy for community-acquired pneumonia.5
“[Patients] had to have received three days of a beta-lactam and meet variable clinical stability criteria,” Spivak said. “If those were met, patients were randomized to five days more of amoxicillin clavulanate or five days of placebo.”
The results were convincing. “At University of Utah, we have actually moved to three days for community-acquired pneumonia in our guidelines and in our order sets for floor patients,” she said. As evidence that shorter duration of antibiotics is a better approach — because it less likely to spur drug resistance or harm the patient — a recent commentary asked, “Can the future of ID escape the inertial dogma of its past?”6
“It really calls on infectious diseases to embrace and understand these dogmas behind what we do, and to embrace the newer literature as a profession that moves things forward,” Spivak said. “And I honestly know many hospitalists, many general medicine practitioners, who treat things for much shorter [durations] with less antibiotics and more oral antibiotics than ID physicians like myself do. I think that’s a detriment to our profession, and this paper is essentially calling on ID to embrace these ideas.”
REFERENCES
- Miles KE, Rodriguez R, Gross AE, Kalil AC. Strength of recommendation and quality of evidence for recommendations in current Infectious Diseases Society of America guidelines. Open Forum Infect Dis 2021;8:ofab033.
- Birchall R, Alexander JE. Medical aspects of pyelonephritis. Medicine (Baltimore) 1950;29:1-28.
- Radetsky M. Hostage to history: The duration of antimicrobial treatment for acute streptococcal pharyngitis. Pediatr Infect Dis J 2017;36:507-512.
- Kaye D, et al. Chapter 56: Urinary Tract Infection. In: Mandell, GL, Douglas RG Jr, Bennett JE, eds. Principles and Practices of Infectious Diseases, 1st Ed. John Wiley and Sons; 1979.
- Dinh A, Ropers J, Duran C, et al. Randomized controlled trial: Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): A double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet 2021;397:1195-1203.
- Davar K, Clark D, Centor RM, et al. Can the future of ID escape the inertial dogma of its past? The exemplars of shorter is better and oral is the new IV. Open Forum Infect Dis 2022;10:ofac706.
Antibiotic therapy is steeped in dogma from case-series studies conducted in the 1940s and 1950s, which generated “low-quality” but persistent evidence before the era of widespread clinical trials, Emily Spivak, MD, said at the 2023 conference of the Society for Healthcare Epidemiology of America.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content