Should You Consider Antibiotics for Exacerbations of Mild COPD?

PRACTICE CHANGER

Consider antibiotics for patients with exacerbations of mild to moderate chronic obstructive pulmonary disease (COPD).¹

STRENGTH OF RECOMMENDATION

B: Based on a single well-done multicenter randomized controlled trial (RCT) with quality evidence.¹

ILLUSTRATIVE CASE

A 45-year-old man with a history of mild COPD seeks treatment for worsening dyspnea and increased (nonpurulent) sputum production. He denies fever or chills. On exam, he has coarse breath sounds and scattered wheezes. Should you add antibiotics to his treatment?

COPD exacerbations—a worsening of symptoms beyond day-to-day variations that leads to a medication change—are part of the disease course and can accelerate lung function decline, decrease quality of life, and, when severe, increase mortality.² Infections cause an estimated 50% to 70% of COPD exacerbations.^2-4

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend using antibiotics to treat exacerbations in patients with moderate or severe COPD who

• Have increased dyspnea, sputum volume, and sputum purulence;

• Have two of these symptoms if increased sputum purulence is one of them; or

• Require mechanical ven­tilation.²

According to the GOLD guidelines, the choice of antibiotic should be based on local antibiograms; common options include amoxicillin, amoxicillin/clavulanate, azithromycin, and doxycycline.² Although the GOLD guidelines cover use of antibiotics for COPD exacerbations, this recommendation is based on analyses of studies that focused on patients with moderate or severe COPD.² There has been little research on using antibiotics for exacerbations of mild COPD.

STUDY SUMMARY

Using antibiotics often resolves symptoms

Llor et al¹ conducted a multicenter, double-blind, placebo-controlled RCT to examine the effectiveness of antibiotic treatment for COPD exacerbations. Participants (ages 40 and older) had mild to moderate COPD, defined as 10 or more pack-years of smoking, an FEV₁ greater than 50%, and an FEV₁/FVC ratio lower than 0.7. An exacerbation was defined as at least one of the following: increased dyspnea, increased sputum volume, or sputum purulence.

Patients were randomly assigned to receive amoxicillin/clavulanate 500/125 mg or placebo three times a day for eight days. Primary endpoints were clinical cure (resolution of symptoms) and clinical success (resolution or improvement of symptoms) at days 9 to 11, as determined by physician assessment. Secondary measures included cure and clinical success at day 20 and time until next exacerbation. Patients were monitored for one year after the exacerbation.

There were 162 patients in the antibiotic group and 156 in the placebo group; the two groups were demographically similar. In each group, four patients withdrew consent and were removed from analysis. By the 9-to-11-day follow-up visit, 74.1% of patients in the antibiotic group had clinical cure, compared with 59.9% in the placebo group (number needed to treat [NNT] = 7). Clinical success also was significantly greater with antibiotics compared with placebo (90.5% vs 80.9%).

The clinical cure rate at day 20 also was significantly greater in patients on antibiotics compared with placebo (81.6% vs 67.8%; NNT = 7). During the one-year follow-up, 58% of patients in the antibiotic group and 73.2% of those in the placebo group experienced additional exacerbations. Time to next exacerbation was significantly longer in patients taking antibiotics (233 days vs 160 days).

Can CRP level help determine who should receive antibiotics?

Previous studies have identified biomarkers, including C-reactive protein (CRP), that indicate COPD exacerbation but have not linked them to clinical course.^5-7 In this study, researchers measured CRP in patients receiving placebo to determine if this biomarker could predict clinical outcomes.

The researchers found that the clinical success rate among patients with a CRP lower than 40 mg/L was 87.6%, while only 34.5% of patients with a CRP greater than 40 mg/L experienced clinical success (sensitivity and specificity for clinical success at this cutoff were 0.655 and 0.876, respectively). This suggests that antibiotics might be appropriate for patients with an exacerbation of mild or moderate COPD who have a CRP greater than 40 mg/L.

There were 35 adverse events: 23 in the antibiotics group and 12 in the placebo group. Two patients in the antibiotics group discontinued treatment as a result. Most adverse events involved mild gastrointestinal problems.

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