Antibiotic Resistance
Corey Diamond, PharmD
The “postantibiotic era” is not coming—it is already here. The ubiquity of lower respiratory tract infections makes community acquired pneumonia (CAP) an evident target in limiting antimicrobial exposure. Results from a new study, published in April 2021 in the Lancet by Dinh and colleagues, boasts success for patients with a 3-day CAP treatment course. The results provide more evidence to support guidance from the Infectious Diseases Society of America (IDSA), the American Thoracic Society (ATS), and the American College of Physicians (ACP) that shorter courses of therapy may be as effective as
traditional-length courses.
Study findings
Dinh and colleagues conducted a double-blind, randomized, placebo-controlled trial—with a noninferiority margin of 10%—that included over 300 non-ICU hospitalized patients admitted for CAP. All patients received a 3-day course of beta-lactam antibiotics. They were then randomly assigned to receive 5 extra days of placebo or oral amoxacillin-clavulanate three times daily. The research team found no significant difference in clinical cure rates between the placebo group and the extended treatment group, with an absolute risk difference of about 9% between the respective groups.
The study’s primary efficacy endpoint was meeting clinical cure criteria, defined by apyrexia (temperature ≤ 37.8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause—15 days after the patient’s first antibiotic intake.
State of affairs
For several years now, clinical guidelines have recommended 5 days of antibiotic treatment for uncomplicated CAP. However, a May 2018 Clinical Infectious Diseases study by Yi and colleagues of more than 150,000 hospitalized patients with CAP in the United States found a median duration of antibiotic therapy of 9.5 days, exceeding the recommended therapy course in over 70% of the cases.
Currently, the 2019 clinical practice guidelines from ATS and IDSA recommend a minimum of 5 days of antibiotic treatment for hospitalized patients with CAP, provided they meet certain clinical stability criteria, such as afebrile for at least 48 hours with no signs of extrapulmonary infection.
In April 2021, ACP published a narrative review in the Annals of Internal Medicine that incorporated recent guidelines and peer-reviewed studies. The organization recommended a 5-day treatment course of antibiotics for CAP. Of note, the review used the study by Dinh and colleagues as one of the main references for this justification, stating that the authors’ data “suggest that 5 days may be too long in some cases of CAP.”
Caveats
Shortcomings in the methodology of the study by Dinh and colleagues may give some clinicians pause. First, the authors did not investigate or control for the true etiology of the patient’s pneumonia. A study by Jain and colleagues published in the New England Journal of Medicine in 2015 found that approximately 27% of CAPs requiring hospitalization have a viral etiology. Thus, it is possible the duration of antibiotic treatment for either treatment arm in the Dinh and colleagues study—especially considering the extended therapy arm tended to have lower procalcitonin levels when measured—would have had no effect on the outcome, skewing the results.
Second, the authors’ use of beta-lactam monotherapy (i.e., not including additional macrolide or fluroquinolone therapy in combination) introduces potential bias from atypical bacterial CAP infections, which, although relatively uncommon, comprise about 15% of all CAPs.
Dinh and colleagues’ data by itself do not present a compelling argument for routinely recommending a 3-day course of antibiotic treatment in hospitalized patients. Considering the main comparator for this study is an 8-day course rather than a 5-day course, it does not inform as well as it could as a basis of comparison with current recommendations.
However, for what it lacks in design quality, it makes up for in its value as a hypothesis generator. Very few studies in the current literature investigate a 3-day treatment course for patients hospitalized with CAP. Dinh and colleagues’ data are yet another step in the right direction for bolstering antimicrobial stewardship techniques and pave the way for future studies to justify investigating shorter courses of therapy in similar settings.