When are antibiotics indicated for acute COPD exacerbations?

Evidence summary

A recent Cochrane review identified 11 randomized controlled trials (RCTs) (with a total of 917 patients) addressing antibiotic therapy for COPD exacerbations characterized by 1 or more of the following: an increase in sputum purulence or volume, dyspnea, wheezing, chest tightness, or fluid retention.¹ Eight trials were conducted on hospital wards, 1 was in a medical intensive care unit, and 2 trials were in the outpatient setting. Antibiotics were given orally in 9 of the 11 studies.

Overall, antibiotics reduced risk of short-term mortality by 77% (relative risk [RR]=0.23; 95% confidence interval [CI],0.10–0.52; number needed to treat [NNT]=8), treatment failure by 53% (RR=0.47; 95% CI, 0.36–0.62; NNT=3), and sputum purulence by 44% (RR=0.56; 95% CI, 0.41–0.77; NNT=8). A subgroup analysis that excluded the outpatient and intensive-care unit studies did not change the result. Another subgroup analysis of the 2 outpatient studies failed to find a significant effect, although the studies had very different designs.

These findings are more robust than those of an earlier, lower-quality meta-analysis of 9 randomized controlled trials (RCTs) with 1101 patients with presumed COPD, which also compared antibiotic therapy with placebo for acute exacerbations.² Specific diagnostic criteria were not stated for the diagnosis of either COPD or an acute exacerbation. No single outcome measure was common to all studies. The authors found a summary beneficial effect size of antibiotic therapy of 0.22 (95% CI, 0.10–0.34), which is generally interpreted as small. One clinical parameter, peak expiratory flow rate (PEFR), was reported in 6 of the studies. Antibiotic therapy resulted in an average 10.75 L/min improvement in PEFR compared with placebo (95% CI, 4.96–16.54 L/min).

Two RCTs addressing antibiotic use in the outpatient setting were identified in the Cochrane review. One double-blind crossover trial performed in Canada compared antibiotic with placebo therapy for 173 outpatients with 362 exacerbations classified according to severity.³ The protocol used oral trimethoprim-sulfamethoxazole, amoxicillin, or doxycycline (according to the attending physician’s preference) or a look-alike placebo. Symptom resolution was seen by 21 days in 68% of antibiotic users vs 55% of those on placebo (P<.01, NNT=8). Ten percent of patients taking antibiotics deteriorated to the point where hospitalization or unblinding of the therapy was necessary, compared with 19% in the placebo group (P<.05, NNT=11).

For patients with all 3 cardinal COPD symptoms (increased dyspnea, sputum production, and sputum purulence) at enrollment, there was resolution at 21 days in 63% with antibiotics vs 43% for placebo (P value not given). Antibiotics did not benefit patients with 1 cardinal symptom (74% success with antibiotics vs 70% on placebo; P value not given).

The Cochrane review also identified a Danish RCT that studied 278 patients presenting to their general practitioners with subjective acute worsening of their COPD. Patients were randomized to 7 days of oral amoxicillin or placebo. There was no difference between the groups in terms of symptom resolution at 1 week (odds ratio=1.03, favoring placebo; 95% CI, 0.75–1.41) or in changes in PEFR (weighted mean difference=–0.89, favoring placebo; 95% CI, –29 to 27 L/min).

Recommendations from others

The Veterans Health Administration recommends antibiotics if a patient with COPD has changes in sputum volume or quality as well as increased dyspnea, cough, or fever; infiltrate on x-ray suggesting pneumonia should be treated as such.⁴

The American College of Chest Physicians recommends that with severe COPD exacerbations, narrow spectrum antibiotics are reasonable first-line agents.⁵ They also note that the superiority of newer, more broad-spectrum antibiotics has not been established.

Evidence summary

A recent Cochrane review identified 11 randomized controlled trials (RCTs) (with a total of 917 patients) addressing antibiotic therapy for COPD exacerbations characterized by 1 or more of the following: an increase in sputum purulence or volume, dyspnea, wheezing, chest tightness, or fluid retention.¹ Eight trials were conducted on hospital wards, 1 was in a medical intensive care unit, and 2 trials were in the outpatient setting. Antibiotics were given orally in 9 of the 11 studies.

Overall, antibiotics reduced risk of short-term mortality by 77% (relative risk [RR]=0.23; 95% confidence interval [CI],0.10–0.52; number needed to treat [NNT]=8), treatment failure by 53% (RR=0.47; 95% CI, 0.36–0.62; NNT=3), and sputum purulence by 44% (RR=0.56; 95% CI, 0.41–0.77; NNT=8). A subgroup analysis that excluded the outpatient and intensive-care unit studies did not change the result. Another subgroup analysis of the 2 outpatient studies failed to find a significant effect, although the studies had very different designs.

These findings are more robust than those of an earlier, lower-quality meta-analysis of 9 randomized controlled trials (RCTs) with 1101 patients with presumed COPD, which also compared antibiotic therapy with placebo for acute exacerbations.² Specific diagnostic criteria were not stated for the diagnosis of either COPD or an acute exacerbation. No single outcome measure was common to all studies. The authors found a summary beneficial effect size of antibiotic therapy of 0.22 (95% CI, 0.10–0.34), which is generally interpreted as small. One clinical parameter, peak expiratory flow rate (PEFR), was reported in 6 of the studies. Antibiotic therapy resulted in an average 10.75 L/min improvement in PEFR compared with placebo (95% CI, 4.96–16.54 L/min).

Two RCTs addressing antibiotic use in the outpatient setting were identified in the Cochrane review. One double-blind crossover trial performed in Canada compared antibiotic with placebo therapy for 173 outpatients with 362 exacerbations classified according to severity.³ The protocol used oral trimethoprim-sulfamethoxazole, amoxicillin, or doxycycline (according to the attending physician’s preference) or a look-alike placebo. Symptom resolution was seen by 21 days in 68% of antibiotic users vs 55% of those on placebo (P<.01, NNT=8). Ten percent of patients taking antibiotics deteriorated to the point where hospitalization or unblinding of the therapy was necessary, compared with 19% in the placebo group (P<.05, NNT=11).

For patients with all 3 cardinal COPD symptoms (increased dyspnea, sputum production, and sputum purulence) at enrollment, there was resolution at 21 days in 63% with antibiotics vs 43% for placebo (P value not given). Antibiotics did not benefit patients with 1 cardinal symptom (74% success with antibiotics vs 70% on placebo; P value not given).

The Cochrane review also identified a Danish RCT that studied 278 patients presenting to their general practitioners with subjective acute worsening of their COPD. Patients were randomized to 7 days of oral amoxicillin or placebo. There was no difference between the groups in terms of symptom resolution at 1 week (odds ratio=1.03, favoring placebo; 95% CI, 0.75–1.41) or in changes in PEFR (weighted mean difference=–0.89, favoring placebo; 95% CI, –29 to 27 L/min).

Recommendations from others

The Veterans Health Administration recommends antibiotics if a patient with COPD has changes in sputum volume or quality as well as increased dyspnea, cough, or fever; infiltrate on x-ray suggesting pneumonia should be treated as such.⁴

The American College of Chest Physicians recommends that with severe COPD exacerbations, narrow spectrum antibiotics are reasonable first-line agents.⁵ They also note that the superiority of newer, more broad-spectrum antibiotics has not been established.

Evidence summary

A recent Cochrane review identified 11 randomized controlled trials (RCTs) (with a total of 917 patients) addressing antibiotic therapy for COPD exacerbations characterized by 1 or more of the following: an increase in sputum purulence or volume, dyspnea, wheezing, chest tightness, or fluid retention.¹ Eight trials were conducted on hospital wards, 1 was in a medical intensive care unit, and 2 trials were in the outpatient setting. Antibiotics were given orally in 9 of the 11 studies.

Overall, antibiotics reduced risk of short-term mortality by 77% (relative risk [RR]=0.23; 95% confidence interval [CI],0.10–0.52; number needed to treat [NNT]=8), treatment failure by 53% (RR=0.47; 95% CI, 0.36–0.62; NNT=3), and sputum purulence by 44% (RR=0.56; 95% CI, 0.41–0.77; NNT=8). A subgroup analysis that excluded the outpatient and intensive-care unit studies did not change the result. Another subgroup analysis of the 2 outpatient studies failed to find a significant effect, although the studies had very different designs.

These findings are more robust than those of an earlier, lower-quality meta-analysis of 9 randomized controlled trials (RCTs) with 1101 patients with presumed COPD, which also compared antibiotic therapy with placebo for acute exacerbations.² Specific diagnostic criteria were not stated for the diagnosis of either COPD or an acute exacerbation. No single outcome measure was common to all studies. The authors found a summary beneficial effect size of antibiotic therapy of 0.22 (95% CI, 0.10–0.34), which is generally interpreted as small. One clinical parameter, peak expiratory flow rate (PEFR), was reported in 6 of the studies. Antibiotic therapy resulted in an average 10.75 L/min improvement in PEFR compared with placebo (95% CI, 4.96–16.54 L/min).

Two RCTs addressing antibiotic use in the outpatient setting were identified in the Cochrane review. One double-blind crossover trial performed in Canada compared antibiotic with placebo therapy for 173 outpatients with 362 exacerbations classified according to severity.³ The protocol used oral trimethoprim-sulfamethoxazole, amoxicillin, or doxycycline (according to the attending physician’s preference) or a look-alike placebo. Symptom resolution was seen by 21 days in 68% of antibiotic users vs 55% of those on placebo (P<.01, NNT=8). Ten percent of patients taking antibiotics deteriorated to the point where hospitalization or unblinding of the therapy was necessary, compared with 19% in the placebo group (P<.05, NNT=11).

For patients with all 3 cardinal COPD symptoms (increased dyspnea, sputum production, and sputum purulence) at enrollment, there was resolution at 21 days in 63% with antibiotics vs 43% for placebo (P value not given). Antibiotics did not benefit patients with 1 cardinal symptom (74% success with antibiotics vs 70% on placebo; P value not given).

The Cochrane review also identified a Danish RCT that studied 278 patients presenting to their general practitioners with subjective acute worsening of their COPD. Patients were randomized to 7 days of oral amoxicillin or placebo. There was no difference between the groups in terms of symptom resolution at 1 week (odds ratio=1.03, favoring placebo; 95% CI, 0.75–1.41) or in changes in PEFR (weighted mean difference=–0.89, favoring placebo; 95% CI, –29 to 27 L/min).

Recommendations from others

The Veterans Health Administration recommends antibiotics if a patient with COPD has changes in sputum volume or quality as well as increased dyspnea, cough, or fever; infiltrate on x-ray suggesting pneumonia should be treated as such.⁴

The American College of Chest Physicians recommends that with severe COPD exacerbations, narrow spectrum antibiotics are reasonable first-line agents.⁵ They also note that the superiority of newer, more broad-spectrum antibiotics has not been established.