Antibiotic therapy was associated with significantly reduced treatment failure in chronic obstructive pulmonary disease (COPD) patients experiencing mild exacerbations, according to a systematic review and meta-analysis.

In 68 randomized controlled trials of patients with moderate to severe exacerbations, antibiotics and systemic corticosteroids were associated with improved symptoms and less treatment failure versus placebo or management without antibiotics.

Specifically, antibiotics given for 3- to 14-days were associated with increased exacerbation resolution (odds ratio 2.03, 95% CI 1.47-2.80, moderate strength of evidence [SOE]) and less treatment failure (OR 0.54, 95% CI 0.34-0.86, moderate SOE), and these findings were independent of exacerbation severity or treatment as outpatient or inpatient, reported Claudia C. Dobler, MD, PhD, of the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery at the Mayo Clinic in Rochester, Minnesota, in Annals of Internal Medicine.

The findings support an earlier systematic review conducted to inform the most recent European Respiratory Society/American Thoracic Society joint guidelines, which found antibiotics to be beneficial in the treatment of COPD exacerbations.

But the new analysis includes three additional trials that had outpatients with mild to moderate exacerbations.

In an interview with MedPage Today, co-author Michael E. Wilson, MD, also of the Mayo Clinic, noted that in clinical practice, antibiotics are often not given to patients with mild exacerbations unless they have symptoms, such as high sputum production or frequent cough.

“If patients are not experiencing these symptoms [clinicians] may be inclined to manage exacerbations with steroids and bronchodilator without antibiotics,” he said. “This review would suggest that patients with mild, as well as moderate and severe, exacerbations may benefit from treatment with antibiotics even if they don’t have these symptoms.”

The randomized trials included in the analysis evaluated exacerbation drug therapies among COPD patients treated as outpatients or who were hospitalized outside of ICUs. The analysis compared various drug treatments with placebo, usual care, or other pharmacologic interventions.

The authors reported that systemic corticosteroids given for 9 to 56 days were associated with less treatment failure (OR 0.01, 95% CI 0.00-0.13, low SOE). Treatment with systemic corticosteroids was associated with a higher number of total and endocrine-related adverse events (AEs) versus placebo.

There was insufficient evidence showing either no effect or inconclusive effects or improvement in lung function for other drug interventions examined, including aminophylline, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators.

Three studies that compared outcomes with short- and longer duration systemic corticosteroid treatment (3 vs 10 days; 5 vs 14 days; and 2 vs 8 weeks), failed to show better improvement in exacerbation outcomes with the longer treatment regimens.

“The results are similar to those of previous systematic reviews and support the use of shorter regimens of systemic corticosteroids,” the researchers wrote.

A single 2017 study included in the analysis compared inhaled corticosteroids to systemic corticosteroids for COPD exacerbations, finding inhaled corticosteroids to be noninferior to systemic treatment for clinically meaningful outcomes.

“Systemic steroids are a mainstay of treatment, but they are also associated with a lot of adverse events,” Wilson said, adding that the single-study findings are intriguing and merit further study.

The analysis of studies examining treatment with aminophyllines showed no improvements in effectiveness outcomes, but it did show an increase in gastrointestinal AEs associated with the treatment.

“These updated findings support the results of a Cochrane systematic review published in 2003,” the authors wrote. “Magnesium sulfate, erdosteine, simvastatin and zileuton, which showed improved FEV1, need to be assessed in large, high-quality randomized clinical trials with clinical outcomes.”

Study limitations included the inclusion of only a single trial or two trials for certain drug interventions, “which limits inference from the quantitative synthesis,” as well as the exclusion of trials that were published in languages other than English. And the exclusion of patients receiving treatment in ICUs means the findings may not be easily extrapolated to the sickest patients, they stated.

The researchers mentioned several ongoing randomized trials that could inform the treatment of COPD exacerbations, including “a study comparing low- and high-dose corticosteroids (NCT02294734, recruiting), a study comparing 3 versus 5 days of oral corticosteroids (NCT04075331, recruiting), and studies comparing biological therapies with placebo or usual care (NCT04098718 and NCT04075331, not yet recruiting).”

“Our review found a lack of good-quality, reliable evidence to answer many of the important clinical questions surrounding treatment of patients with exacerbation of COPD,” they concluded. “Future studies should focus on high-quality study design and patient-centered outcomes — particularly clinical resolution of exacerbation and risk for repeated exacerbation, rather than lung function measurements.”

Last Updated February 24, 2020