Applying ACP's advice for shorter courses of antibiotics

Antibiotic prescribing practices in the real world aren't always based on solid evidence.

“Many clinicians default to standard durations of seven days or 10 days based on archaic studies,” said Rachael Lee, MD, MSPH, a health care epidemiologist and an assistant professor in the division of infectious diseases at the University of Alabama at Birmingham. “We may provide longer prescriptions in hopes of preventing development of antibiotic resistance; however, there is no evidence that taking antibiotics beyond symptom resolution reduces resistance.”

In fact, resistance to antibiotics happens after prolonged use of antibiotics, and newer evidence has shown that shorter durations of antibiotics are a better choice for many common infections, said Amir Qaseem, MD, PhD, FACP, Vice President of Clinical Policy for ACP. “Generally, for many of these bacterial infections, shorter courses of antibiotics have shown to result in pretty similar clinical outcomes and less adverse reactions than longer courses,” he said.

Clinicians wrote around 250 million outpatient oral antibiotic prescriptions in 2018, and nearly 50% of all antibiotic use in the outpatient setting may be unnecessary or inappropriate in selection, dosing, or duration, according to the CDC. On the flip side, appropriate antibiotic prescribing encompasses four Rs every internist should remember, Dr. Qaseem said. “What I always say is, ‘You give the right antibiotic at the right dose for the right duration for the right condition.’”

To help internists better understand when to use short-course antibiotics, Drs. Lee and Qaseem coauthored ACP's recent Best Practice Advice, which was published in April by Annals of Internal Medicine. The paper is ACP's second guidance on the topic of antibiotic stewardship, Dr. Qaseem noted. In March 2016, the College partnered with the CDC to publish advice for high-value care with regard to appropriate antibiotic use for adult patients with acute respiratory tract infection.

ACP took on this topic to improve patient care and combat antibiotic resistance, said Dr. Qaseem. “Inappropriate antibiotic use is one of the most important contributors when it comes to antibiotic resistance, and it is a public health threat, as CDC has recognized,” he said. “Reducing inappropriate prescribing will improve quality of care, reduce antibiotic resistance, and decrease health care costs.”

The new advice, which is geared to all clinicians who prescribe antibiotics, outlined the appropriate duration of short-course antibiotics when treating the following four common bacterial infections in both inpatient and outpatient settings: chronic obstructive pulmonary disease (COPD) exacerbation and acute uncomplicated bronchitis, community-acquired pneumonia (CAP), uncomplicated urinary tract infection, and cellulitis.

For adults with COPD exacerbation and acute uncomplicated bronchitis who have clinical signs of a bacterial infection, clinicians should limit antibiotic treatment duration to five days, according to the paper.

“In order to even deserve antibiotics, you need to have dyspnea, purulent sputum, and increased sputum—at least two of those three. This is not someone who does not have COPD who has bronchitis, because we do not recommend antibiotics for them, and good studies have shown that five days is enough,” said Best Practice Advice coauthor Robert M. Centor, MD, MACP, during a May episode of the podcast series “Annals On Call,” which covered the new guidance.

In patients with CAP, ACP advised clinicians to prescribe antibiotics for a minimum of five days, with any extension guided by validated measures of clinical stability. “There's a recent study that suggests that three days is probably good enough … but no more than five days if the patient is stable,” Dr. Centor said. “If the patient is not stable, No. 1, rethink your diagnosis, and No. 2, continue the antibiotics.”

In women with uncomplicated bacterial cystitis, clinicians should prescribe nitrofurantoin for five days, trimethoprim-sulfamethoxazole for three days, or fosfomycin as a single dose, the ACP advice said. In men and women with uncomplicated pyelonephritis, clinicians should prescribe five to seven days of fluoroquinolones or 14 days of trimethoprim-sulfamethoxazole, based on antibiotic susceptibility.

“There is data for seven days in trimethoprim-sulfamethoxazole, although there aren't enough [randomized controlled trials] yet, I think, to really push the needle, so we recommended 14 days,” Dr. Lee said during the “Annals on Call” episode.

Finally, in patients with an accurate diagnosis of nonpurulent cellulitis, clinicians can use a five- to six-day course of antibiotics active against streptococci. “And you really want to make sure that your patients have close follow-up and are able to self-monitor, and you can give them those signs to watch out for,” Dr. Lee said.

She said she believes the College's advice will help clinicians optimize their use of antibiotics and decrease unnecessary use. “We hope that this guidance clearly defines the patient population in need of antibiotics and internists feel confident in the shorter duration of antibiotics prescribed,” Dr. Lee said.

Indeed, the paper will help internists move toward evidence-based, safer, equally effective antibiotic treatments, said infectious diseases subspecialist Brad Spellberg, MD, FACP, who is chief medical officer at the Los Angeles County-University of Southern California Medical Center.

“It is great when a specialty society has the courage to challenge convention and drive clinical practice forward based on data, and ACP has done that again,” he said.

Dr. Spellberg, who has advocated for shortening antimicrobial courses over the past decade, noted that Louis B. Rice, MD, FACP, first called out the need to move to short-course therapy in a February 2008 paper published in Clinical Infectious Diseases. Together, the two wrote “Duration of Antibiotic Therapy: Shorter Is Better,” an editorial published in August 2019 by Annals.

“As [Dr.] Rice has said, ‘It is hard to get doctors to not give antibiotics at all. It is much easier to convince them to give antibiotics for shorter periods of time,’” Dr. Spellberg said. “This is his cause that we have all taken on, and ACP has taken an important milestone into making Dr. Rice's vision a reality.”

For Dr. Rice, who is chair of the department of medicine at the Warren Alpert Medical School of Brown University in Providence, R.I., the College's advice is a step in the right direction.

“Sadly, in many parts of the country and the world, prescriptions still conform to seven-, 10-, 14-, or 21-day courses, regardless of what studies show,” he said. “The ACP Best Practice advice is based on a solid, growing, and almost universally consistent group of studies that suggest shortening antimicrobial courses is safe and effective … [and] will further establish shortened courses as the standard of practice, rather than a risky idea.”

However, Dr. Rice did note that the guidance will not eliminate unnecessary antibiotic use, which often results from treating conditions that require no antibiotics in the first place, such as colds and allergies. “Having said that, it will be a good thing if an unnecessary antibiotic course is for five rather than seven days,” he said.

During the “Annals On Call” episode, Dr. Spellberg shared that he tries to use humor to break clinicians of prescribing longer courses of antibiotics, calling the old standard of seven-day intervals “Constantine units.” He said when he was in medical school, he was taught to prescribe two Constantine units of antibiotics to treat CAP.

“‘Why are you giving 14 days? Because Constantine the Great in 321 AD said there'd be seven days in a week. If he said there were four days in a week, you'd be giving eight days,’” he said he tells clinicians. “People start laughing, and they start realizing how silly it is.”

A remaining challenge will be lingering patient demand for antibiotic therapy, noted Dr. Qaseem, so patient education will be key when internists implement this guidance in real-world practice.

“Physicians can control and prescribe antibiotics appropriately, but they can't do it alone. … We need a multidimensional approach that includes patient and public education, [and] we need to disseminate the educational materials to the community,” he said. “One of the issues that keeps on coming up is that physicians don't have enough time … but I think just sitting down and talking to your patient regarding the benefits and harms does make a difference.”