The Duration of Antibiotics: Why Short Is Good in the Long Run

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“Take these pills for 10 days, even if you feel better sooner.” I vividly recall how, in years past, I would impress upon patients the importance of completing an entirely long antibiotic course. My mind’s eye beheld the specter of a half-treated infection raging back in fuller force and powered by newly resistant organisms. Now we know better: The shortest effective course is the way to reduce the risk of patient adverse drug events, antimicrobial resistance, and unnecessary health care costs.

According to the CDC, clinicians prescribed 211 million outpatient antibiotic prescriptions in 2021, which is equivalent to 636 prescriptions for every 1000 individuals, though prescribing rates varied widely by state.¹ Once an antibiotic prescription is started, every additional day of use holds the potential for the added risk of adverse events (AEs) for the patient. A study of inpatients with pneumonia² revealed that antibiotics prescribed at discharge were often excessive in duration, and that each day of excess treatment was linked to a 5% increase in antibiotic-related AEs. Although some AEs, such as anaphylaxis, occur early in a treatment course regardless of intended duration, the risk for AEs, such as hepatotoxicity, nephrotoxicity, and some gastrointestinal effects, changes to the microbiome, and specific drug interactions, can compound over time.

Each additional day of antibiotic exposure also holds the potential to contribute to the emergence of antimicrobial resistance in the patient’s community. More prolonged exposure affords more opportunities for resistance to develop and for natural selection to favor resistant organisms that can then spread to new hosts. Drug-specific pharmacokinetics are also a factor in considering course duration. For example, the elimination half-life for a drug like azithromycin is significantly longer than some other antibiotics so that appropriate courses may be shorter.

New data on the noninferiority of shorter courses emerge yearly for common infections like pneumonia, sinusitis, urinary tract infection, and cellulitis. In 2021, the American College of Physicians³ recommended limiting antibiotic durations to 5 days for chronic obstructive pulmonary disease exacerbations and acute uncomplicated bronchitis. They also recommended 5 days for community-acquired pneumonia, considering an extension based on clinical signs.

It takes time for new evidence to translate into practice changes; the lag time between the “lab bench and the bedside” might average 17 years for health care interventions, per one estimate⁴ or a median duration of 10 days for most conditions studied. Investigators noted that typical durations exceeded those recommended in clinical practice guidelines available at that time, including excessively long courses for sinusitis, community-acquired pneumonia, cellulitis, and cystitis.

Duration of therapy isn’t the only vital component of antibiotic prescribing. The CDC estimates⁵ that up to half of outpatient antibiotic use is inappropriate in 1 or more ways, including inappropriate duration, dosing, antibiotic choice, as well as unnecessary use of an antibiotic in the first place. In choosing an antibiotic, prescribers are often encouraged to incorporate local antimicrobial resistance and susceptibility patterns into their decision-making. Historically, these data have been hard to find outside the hospital setting. The new Bugs + Drugs feature in the epocrates mobile app offers free geolocalized ambulatory setting antimicrobial susceptibility data on urinary and skin/soft-tissue organisms centered on any zip code in the US.

Indeed, some patients with underlying conditions or other clinical factors may warrant a longer duration of antibiotics. However, long durations—regardless of patient characteristics, infection type, specific antibiotic, and local resistance patterns—are no longer supported by recent evidence. The CDC and major specialty societies concur that the shortest effective antibiotic duration is the one that provides the best outcome for patients and their communities. Reduced AEs translate into reduced unnecessary health care costs. It’s not always the case that a single change in how we practice can benefit individuals and society; this is one of those changes where incentives are well aligned. It’s no wonder that the refrain of “shorter is better” is increasingly inspiring changes to antibiotic prescribing in both inpatient and outpatient settings.

This article is intended for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.

References

• Outpatient antibiotic prescriptions — United States, 2020 | antibiotic use | CDC. Published October 24, 2022. Accessed April 14, 2023. https://www.cdc.gov/antibiotic-use/data/report-2021.html
• Vaughn VM, Flanders SA, Snyder A, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: a multihospital cohort study. Ann Intern Med. 2019;171(3):153-163. doi:10.7326/M18-3640
• Lee RA, Centor RM, Humphrey LL, et al. Appropriate use of short-course antibiotics in common infections: best practice advice from the American College of Physicians. Ann Intern Med. 2021;174(6):822-827. doi:10.7326/M20-7355
• Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis. 2008;46(4):491-496. doi:10.1086/526535
• Measuring outpatient antibiotic prescribing. CDC. Reviewed October 5, 2022. Accessed April 5, 2023. https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html