‘Shorter is better’ mantra begins to change antibiotic prescribing
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The optimal duration of antibiotic therapy has been a matter of some debate, and increasingly, research is showing that shorter durations are just as effective as longer courses for many infections.
“Practice is starting to change, and the American College of Physicians (ACP) even released a position paper last year indicating that short-course therapy is now standard of care for many infections,” Brad Spellberg, MD, chief medical officer at the Los Angeles County + University of Southern California Medical Center, told Healio | Infectious Disease News. “That’s the largest specialty society in the U.S. making that statement. The rest of change is simply getting over inertia.
According to Spellberg, studies have shown that it takes doctors an average of 15 to 20 years to change their practice following the publication of definitive research.
“The first public description of what evolved into the ‘shorter is better’ movement was Lou Rice’s 2008 keynote lecture at the Infectious Diseases Society of America annual meeting. So, 14 years ago,” Spellberg said. “Right on time — change is now happening.”
Spellberg, who keeps a widely cited “shorter is better” table of randomized controlled trial (RCT) outcomes on his personal website (see the Table), believes that within 10 years, most physicians will be prescribing short-course therapy where indicated.
According to experts, reducing antibiotic durations can limit resistance genes in patients and avoid other harmful side effects. We spoke with Spellberg and others about the adjustments that have already been made in antibiotic prescribing and what may be needed to facilitate lasting change in practice.
‘Changing landscape’
The ACP position paper, titled “Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice from the American College of Physicians,” was published in 2021 to encourage prescribers to use shorter courses of antibiotics when appropriate by providing guidance.
According to Rachael A. Lee, MD, MSPH, a health care epidemiologist and associate professor in the division of infectious diseases at the University of Alabama at Birmingham (UAB) and lead author of the paper, the recommendations were initially prompted by the need to reach general internists who prescribe antibiotics in 10% of outpatient visits, thus playing a key role in antimicrobial stewardship.
Lee said the infections described in the paper — bronchitis in patients with chronic obstructive pulmonary disease (COPD), community-acquired pneumonia (CAP), pyelonephritis and cellulitis, to name a few — comprise a large proportion of infections encountered in both inpatient and outpatient settings.
“In the past 25 years, nearly 30 randomized controlled trials have been performed comparing short- vs. long-course antibiotics for these infections,” Lee told Healio | Infectious Disease News. “The ACP felt that it was important to provide guidance to clinicians given the changing landscape of evidence in favor of shorter courses.”
Overall, the paper recommended:
- clinicians limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated bronchitis who have clinical signs of a bacterial infection;
- clinicians prescribe antibiotics for CAP for 5 days at a minimum, and duration should be guided by validated measures of clinical stability;
- in women with uncomplicated bacterial cystitis, clinicians prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days or a single dose of fosfomycin;
- in both men and women with pyelonephritis, short-course antibiotics are appropriate based on antimicrobial susceptibility (either 5 to 7 days of fluoroquinolones or 14 days of trimethoprim-sulfamethoxazole); and
- in patients with nonpurulent cellulitis, clinicians should use a 5- to 6-day course of antibiotics with close follow-up.
“I am a huge proponent of ‘shorter is better,’” Lee said. “Prior antibiotic durations were based on case reports and clinical expertise. More than 120 RCTs for a variety of infections have shown that shorter courses are as effective as longer courses.”
Affirming the mantra
This year, Lee and colleagues, including Joshua Stripling, MD, director of the antimicrobial stewardship program at UAB, performed a review of RCTs to determine whether clinical data “affirm the mantra of ‘shorter is better’” for pneumonia, UTI, intra-abdominal infection, bacteremia, skin and soft tissue infection, bone and joint infection, pharyngitis and sinusitis.
“I think [‘shorter is better’] is honestly the future and where we need to go with a lot of our therapies in order to reduce our exposure of patients to antibiotics and to reduce the development of further resistance,” Stripling told Healio | Infectious Disease News. “We really need to be sure that we are set up to utilize new and novel therapies at the appropriate duration to prevent further development of resistance and not do what we've done historically — just provide more antibiotics.”
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The review found that short-course antibiotic durations consistently resulted in similar treatment success rates compared with longer antibiotic courses among patients with the aforementioned infections when the patient’s diagnosis was confirmed, appropriate antimicrobials were used and patients showed clinical signs of improvement.
The studies they reviewed included an RTC published in The Lancet by Dinh and colleagues, in which the researchers randomly assigned 310 patients with moderate-to-severe pneumonia to receive either 3 or 8 days of beta-lactam antibiotic therapy, with the first group receiving placebo after 3 days of treatment. Among 303 patients who remained in the study, 77% in the 3-day treatment group experienced cure by day 15 compared with 68% in the 8-day group — a difference of 9.42% (95% CI, –0.38 to 20.04), which the researchers said indicated noninferiority.
Drekonja and colleagues assessed complicated UTIs in an RCT of 272 men and found that initial UTI symptoms resolved by 14 days after completion of active antibiotic therapy in 93.1% of participants in a 7-day treatment group and 90.2% of participants in a 14-day group, a difference that met the prespecified noninferiority margin of 10%.
Another recent RCT assessing 7 vs. 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia enrolled 604 patients — 306 in the 7-day arm and 298 in the 14-day arm — between January 2013 and August 2017. According to Yahav and colleagues, 45.8% of patients in the 7-day group experienced all-cause mortality, relapse or local suppurative or distant complications, and/or readmission or extended hospitalization compared with 48.3% in the 14-day group, for a risk difference of –2.6% (95% CI, –10.5% to 5.3%).
The STOP-IT trial by Sawyer and colleagues assessed a shorter course of antibiotics — approximately 4 days vs. approximately 8 days — for the treatment of intra-abdominal infections and found that surgical-site infection, recurrent intra-abdominal infection or death occurred in 21.8% patients in the shorter course group compared with 22.3% in the standard course group.
Stripling said efforts are being made to get these data to providers to increase their comfort with shorter courses.
“A lot of this literature ... is getting out to the general prescriber population who prescribe the vast majority of antibiotics,” Stripling said. “I don't think that it is as pressed as it should be, especially in non-ID-related journals, where we're really trying to get that word out a little bit more, and that’s a struggle.”
Lee said she has seen changes in clinical practice and has even implemented them herself because of these and other studies.
“I have consistently chosen shorter courses for these infections with great results for patients,” she said. “I am hopeful we will continue to see practice change for internists and other clinicians.”
Stripling also recommends treatment with shorter courses in his own practice. He said the more physicians prescribe shorter courses, the more comfortable prescribers and patients will become with it.
Lee noted that, to apply these findings to practice, it is important first to know the inclusion criteria of the studies and to have the right diagnosis and right antibiotic prescribed for the patient.
“If a patient is not improving on a regimen, it is important to reassess rather than to default to a longer duration of antibiotics,” Lee said.
‘Just enough is better’
According to C. Buddy Creech, MD, MPH, the Edie Carell Johnson Chair and professor of pediatrics in the division of pediatric infectious diseases at Vanderbilt University School of Medicine, many existing treatment durations are from older recommendations made when there were fewer antibiotic choices, or when those making recommendations did not understand the “individual variability within an infection.”
“I don't know that we can make such a blanket statement that shorter is better, but we do know that we can say ‘just enough is better,’” Creech said. “As we learn more, I think what we're realizing is that we can get more precise with how we treat. One size may not fit all, but that doesn't mean that all the time shorter is better.”
Creech noted that some studies have shown that shorter regimens do not necessarily work. Spellberg includes these exceptions in the table on his website.
One study by Hoberman and colleagues assessing acute otitis media in children aged 6 to 23 months showed that a 5-day regimen of amoxicillin–clavulanate was inferior to a 10-day regimen in resolving the infection and lessening the likelihood of recurrence.
Creech said there are some severe illnesses, such as meningitis, for which there is not a need to try shorter courses “because we know those are some of the sickest patients that we care for.” For others — such as skin abscesses — “we are still anxiously waiting for the data.”
“What it means for us is that we're going to have to study each of these [infections] individually because for some infections, we simply don't treat as long as we used to,” he said.
He reiterated the importance of initiating treatment and prescribing practices that lead to “just the right amount” of therapy. An example of this, Creech said, is osteomyelitis, for which there are data that show patients who recover quickly and whose inflammation begins to resolve quickly do not need as lengthy a course of antibiotics. Two RCTs by Bernard and colleagues and Tone and colleagues demonstrated that shorter courses of antibiotics were noninferior to longer courses for osteomyelitis.
“We’re looking for that Goldilocks amount and duration of antibiotics that treats the infection but does not overtreat it so that we can avoid side effects and changes to the healthy germs that are there,” Creech said.
‘We need to know that we will not cause harm’
According to Stripling, large academic medical centers are more likely to be ahead of the curve on when it comes to reducing antibiotic prescriptions.
“It hasn't really gotten down to the smaller nonacademic hospitals, the rural hospitals, to create that expected practice support,” he said. “As the guidelines are updated, as the recommendations improve from that, and as people have additional support, I think that will improve.”
He said there has also been a push to educate patients on appropriate antibiotic prescribing.
“We've harped on this a lot for viral respiratory infections. The patient comes in and says, ‘I have a cold, I need an antibiotic,’ but we know that the majority of those are caused by viruses, and those antibiotics do absolutely nothing,” he said. “When you tell the patient you only need 3 days of antibiotics, their feeling is, ‘Well, my prior doctor gave me 14 days of antibiotics. Why are you giving me a shorter course?’ I think there really needs to be some more education on the effectiveness and benefits of short-course antibiotics.”
Creech said clinicians who treat children must be “really careful” about not confusing parents.
“We've been telling them for so long to take all the antibiotics we give you so that the infection goes away, and it doesn't come back,” he said. “And now what we're going to be saying to them is, you may not need as much as we've been telling you.”
“We’ve just got to make sure that we speak clearly about what we're trying to do, [which is] have more individualized or personalized infectious diseases care,” he said.
Stripling said it is also important to determine appropriate antibiotic durations for specific populations, such as immunocompromised people, some of whom may be effectively treated with a short course, whereas others may need a longer course.
“I don't know if we've really teased out the difference between who is appropriate for a short course and who may need a longer course of therapy,” he said.
Many prescribers err on the side of caution, sticking with the standard longer course, Stripling said.
“As clinicians, we need to know that we will not cause harm in patients if we choose shorter course antibiotics,” Lee said. “Newer methodologies for shorter duration antibiotic studies have the promise of combining not only clinical outcomes but also patient-specific outcomes, which may help frontline clinicians feel confident in shorter course antibiotics. I believe strong relationships with patients and an ability for follow-up may help clinicians feel confident in the data presented for shorter durations.”
‘Rife with dogma’
Spellberg and Lee collaborated with colleagues on a paper published Dec. 29 in Open Forum Infectious Diseases that provided two examples of historical practices that have been “overturned” by the accumulation of modern studies — longer courses of antibiotic therapy and IV-only therapy for specific infectious syndromes.
“Like all fields of medicine, infectious diseases is rife with dogma that underpins much clinical practice,” they wrote. “These dogmas are based on uncontrolled case series from [more than] 50 years ago, amplified by the opinions of eminent experts.”
Prescribers “must not cling to historical practice simply because ‘that’s the way it’s always been,’” they argued.
“If we can overcome our own resistances, both intrinsic and extrinsic, the specialty of
infectious diseases is ideally positioned to model evidence-based antimicrobial prescribing for trainees, for each other, and for our colleagues in other specialties. With the shared goal of bettering patient care, we believe it is our collective responsibility to lead the way. We owe it to our patients to do so."
References:
- Bernard L, et al. Lancet. 2015;doi:10.1016/S0140-6736(14)61233-2.
- Davar K, et al. Open Forum Infect Dis. 2022;doi:10.1093/ofid/ofac706.
- Dinh A, et al. The Lancet. 2021;doi:10.1016/S0140-6736(21)00313-5.
- Drekonja DM, et al. JAMA. 2021;doi:10.1001/jama.2021.9899.
- Hoberman A, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1606043.
- Lee RA, et al. Annals Intern Med. 2021;doi:10.7326/M20-7355.
- Lee RA, et al. Clin Microbiol Infect. 2022;doi: 10.1016/j.cmi.2022.08.024.
- Sawyer RG, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1411162.
- Spellberg, B. Shorter is better. BradSpellberg.com. Accessed Dec. 28, 2022. https://www.bradspellberg.com/shorter-is-better.
- Tone A, et al. Diabetes Care. 2015;doi:10.2337/dc14-1514.
- Yahav D, et al. Clin Infect Dis. 2019;doi:10.1093/cid/ciy1054.
For more information:
- C. Buddy Creech, MD, MPH, can be reached at buddy.creech@vumc.org.
- Rachael A. Lee, MD, MSPH, can be reached at ralee@uabmc.edu.
- Brad Spellberg, MD, can be reached at spellber@usc.edu.
- Joshua Stripling, MD, can be reached at jstripling@uabmc.edu.
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