Antibiotics for Acute Exacerbation of COPD: It's Still Controversial

Aaron B. Holley, MD


June 06, 2023

In late 2021, the Rome Proposal for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and grading their severity was published. The 2023 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease (GOLD) Report has adopted the Rome Proposal criteria. Given that an endorsement by GOLD is tantamount to acceptance by clinicians, researchers, and policymakers alike, I guess we're all using them now.

Anyone who's ever cared for patients with COPD knows that treatment and reduction of exacerbations is how we improve outcomes. AECOPD are associated with considerable morbidity, greater healthcare utilization and costs, and a long-term decline in lung function. While we hope our pharmacotherapies improve symptoms, we know they reduce AECOPD. If our pharmacotherapies have any impact on mortality, it's probably via AECOPD prevention.

Methods for reducing AECOPD are not controversial, but the approach to AECOPD treatment is, particularly decisions about who gets an antibiotic and who doesn't. Since antibiotic indications are tied to severity, using the Rome Proposal criteria may affect management in unpredictable ways. As such, it's worth reviewing the data on antibiotics for AECOPD.

What Do the Data Reveal?

To start, it's important to note that GOLD doesn't equate having an AECOPD with needing an antibiotic. I myself have conflated the diagnosis with the indication and thereby overprescribed. The bar for diagnosis is quite low. In previous GOLD summaries, any "change in respiratory symptoms" would warrant the AECOPD label. Although the Rome Proposal definition is more specific, it leaves room for liberal interpretation. It's likely to have a greater effect on research than on clinical practice. My guess is that AECOPD prevalence doesn't change.

The antibiotic hurdle is slightly higher than that for diagnosis but is equally open to interpretation. In part, that's related to the inherent subjectivity of judging symptoms, sputum production, and changes in color, but it's also because the data are so poor. The meta-analyses that have been used to establish the indications include fewer than 1000 patients spread across 10 to 11 trials. Thus, the individual trials are small, and the sample size remains nominal even after adding them together. The addition of antibiotics — and it doesn't seem to matter which class, type, or duration — will decrease mortality and hospital length of stay. One study says these effects are limited to inpatients while the other does not. After reading GOLD 2013, GOLD 2023, and both the meta-analyses they used to support their recommendations, I'm still not sure who benefits. Do you have to be hospitalized? Is some sort of ventilatory support required? Does C-reactive protein help or not?

In accordance with the classic Anthonisen criteria, GOLD relies on sputum volume and color as evidence of a bacterial infection. Soon after GOLD 2023 was published, a meta-analysis found that sputum color isn't particularly accurate for detecting bacterial infection. Because it doesn't seem to matter which antibiotic class is used, I always thought we were using antibiotics for their magical, pleiotropic anti-inflammatory effects anyway. I didn't think the presence of an actual bacterial infection was important. If I saw an infiltrate on chest x-ray, I'd change my diagnosis from AECOPD to community-acquired pneumonia (CAP) and switch to CAP coverage. I've been doing this so long that I swear it's in a guideline somewhere, though admittedly I couldn't find said guideline while reading for this piece.

Key Takeaways

In summary, I believe that the guidance reflects the data, which is muddy. The Rome Proposal should be seen as just that — a framework for moving forward with AECOPD classification and antibiotic indications that will need to be refined over time as better data become available. In fact, they allow for a more objective, point-of-care assessment of severity that can be validated and tied to antibiotic benefits. The Rome criteria aren't evidence-based; they're a necessary first step toward creating the evidence.

In the meantime, if your AECOPD patient is hospitalized, they probably warrant an antibiotic. If they're not, sputum changes may be a reasonable surrogate for a bacterial infection. Considerable uncertainty remains.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.