Less Could Be More With Antibiotics for Community-Acquired Pneumonia

Patients with community-acquired pneumonia (CAP) who are clinically stable after three days of antibiotics could do as well with discontinuing or extending the regimen for several days, according to a target trial emulation assessing real-world outcomes.¹ "The short- and longer course antibiotic treatment groups had similar mortality rates, and there was little difference in benefits and harms," report study lead author George Doumat, MD, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, and colleagues.

The target trial emulation design is characterized as "the state-of-the-art observational method for the simulation of RCT (randomized clinical trials)," in an accompanying editorial by Joshua Metlay, MD, PhD and Niteesh Choudhry, MD, PhD, Department of Medicine, Mass General Brigham and Harvard Medical School, Boston, MA.²

This methodology expands on previous observational approaches, Metlay and Choudhry explain, by endeavoring to reproduce its randomized target, "including the incorporation of analytic approaches that account for the 'dynamic' changes of treatments over time based on considerations such as whether patients have reached stability when a treatment change was made."

The investigators sought to emulate the Pneumonia Short Treatment trial, which had determined that antibiotic durations of less than 5 days may be more beneficial than longer durations in patients who are clinically stable by day 3.The investigators point out, however, that this trial had not assessed mortality, and that its sample size limited generalizing the findings to real-world settings.³

In the current study, Doumat and colleagues use a 67-hospital cohort of 5,620 patients hospitalized for CAP in general but not intensive care between February 2017 and July 2024. The investigators ascertained the percentage of patients who would qualify for short therapy per the Pneumonia Short Treatment trial, and determined the difference in 30-day clinical outcomes between those receiving the short versus longer course. The primary outcome was all-cause mortality; with other outcomes including hospital readmissions, urgent clinic visits, and Clostridioides difficile infections.

Doumat and colleagues reported the 30-day adjusted risk ratios for short- versus long-course antibiotic therapy were 0.89 for mortality (95% CI, 0.01-2.25), 1.07 for readmission (0.81-1.42), 0.94 for urgent visit (0.70-1.28), and 1.01 for C. difficile infection (0.18-5.68).

The investigators found that the median antibiotic duration across the cohort was 7 days, with only 7.9% receiving 3 to 4 day regimens. The most common treatments were empiric ceftriaxone (89.3%) or azithromycin (76.9%).

The investigators attribute the relatively small number of patients receiving shorter duration regimens to most having underlying comorbidities, but argue that "no trials to our knowledge have found that longer durations of antibiotic therapy are safer for patients with comorbidities or those who do not meet clinical stability criteria."

They note, however, that current treatment guidelines for CAP in hospitalized patients from the American Thoracic Society and Infectious Diseases Society of America recommend using measures of clinical stability to determine the duration of treatment, and indicate that their findings support these recommendations.

Metlay and Choudhry point out that azithromycin, used in 75% of the cohort, has a prolonged half-life and persistence in lung parenchyma."Thus, we caution about extending these results to other antibiotic treatment regimens, including those that are ß-lactam, cepalosporin, or fluoroquinolone based."

References

1. Doumat G, Ratz D, Horowitz JK, et al. Short versus longer antibiotic duration for commuity-acquired pneumonia. A multicenter target trial emulation. Ann Int Med. 2026, published online April 14.doi:

2. Metlay JP, Choudhry NK. Antibiotics for pneumonia: From evidence to guidelines for action. Ann Int Med. 2026, published online April 14. doi:10.7326/ANNALS-26-00795.

3. Dinh A, Ropers J, Duran, et al. Discontinuing ß-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. doi:10.1016/S0140-6736(21)00313-5.