Antibiotics, systemic corticosteroids reduce treatment failure in COPD

Claudia Dobler

When compared with placebo or no intervention, antibiotics and systemic corticosteroids were associated with less treatment failure in adults with COPD exacerbations, according to a meta-analysis published in the Annals of Internal Medicine.

For their systematic review and meta-analysis, Claudia C. Dobler, MD, PhD, consultant pulmonologist and associate professor of medicine at the Institute for Evidence-Based Healthcare, Bond University in Queensland, Australia, and colleagues evaluated 68 randomized controlled trials involving 10,758 adults with exacerbation of COPD who were treated in inpatient or outpatient settings. The studies compared pharmacologic interventions with placebo, usual care or other pharmacologic interventions.

Benefit of antibiotics, systemic corticosteroids

In studies evaluating systemic antibiotics given for 7 to 10 days vs. placebo or usual care to inpatients or outpatients, antibiotics were linked to increased exacerbation resolution, regardless of exacerbation severity and study setting, at the end of the intervention (OR = 2.03; 95% CI, 1.47-2.8; moderate strength of evidence). In studies of outpatients with mild exacerbations, systemic antibiotics were also associated with less treatment failure at the end of interventions (OR = 0.54; 95% CI, 0.34-0.86; moderate strength of evidence) but not at the longest follow-up of 1 month (OR = 0.82; 95% CI, 0.58-1.14; low strength of evidence). Dyspnea, cough and other symptoms were also reduced with antibiotics in both inpatients and outpatients with mild to moderate or moderate to severe exacerbations.

Similarly, in trials comparing systemic corticosteroids with placebo or usual care in inpatient, outpatient or ED settings, treatment failure was less likely with systemic corticosteroids at the end of interventions lasting 9 to 56 days (OR = 0.01; 95% CI, 0-0.13; low strength of evidence), regardless of treatment setting or exacerbation severity. Dyspnea was also reduced at the end of 7 to 9 days of treatment in outpatients with mild and inpatients with moderate to severe exacerbations. Systemic corticosteroids were, however, linked to increased numbers of total and endocrine-related adverse events. 

“Based on our findings, I would reassure physician colleagues that they should use antibiotics and systemic corticosteroids in any exacerbation of COPD, even if only mild, and not feel guilty about it (at a time when antibiotic stewardship is rightly promoted),” Dobler told Healio Pulmonology. “It is likely that in the future we will be able to determine better which patients stand to benefit the most from these interventions and which patients might not benefit (based on biomarkers including C-reactive protein or procalcitonin for antibiotics and blood eosinophils for systemic corticosteroids), but I do not think that we are quite there yet.”

More evidence necessary

Unfortunately, conclusive data on the preferred choice of antibiotic or corticosteroid regimens were lacking, according to the researchers, as was evidence regarding use of other pharmacologic treatments, including aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids and short-acting bronchodilators.

Dobler said she would discourage physicians from using unproven treatments, such as aminophyllines and magnesium sulfate, but expressed surprise over the lack of data for pharmacologic interventions for COPD overall.

“Despite the large body of literature on COPD, I was surprised to see that for many pharmacologic interventions for exacerbation of COPD that there is insufficient or only weak evidence,” Dobler said. “In clinical practice, for example, we routinely use short-acting bronchodilators to relieve breathlessness during an exacerbation of COPD. This includes short-acting muscarinic antagonists (ipratropium) and short-acting beta agonists (salbutamol). Our study showed that despite the common use of these inhalers, there is no conclusive evidence whether a combination of the two is more effective in relieving breathlessness than any of them alone.”

In addition to more high-quality research, reliable research on pharmacologic treatments, Dobler noted other types of interventions may warrant study.

“There is increasing evidence that some non-pharmacologic therapies, especially exercise started early during an exacerbation, may lead to functional improvements in hospitalized patients with moderate to severe exacerbation of COPD. The American Thoracic Society/European Respiratory Society guidelines published in 2017 included a conditional recommendation (very low quality of evidence) to not start pulmonary rehabilitation during hospitalization for exacerbation of COPD, but since then some new evidence has emerged and we need large high-quality studies that test the effectiveness of early exercise in exacerbation of COPD,” Dobler told Healio Pulmonology. – by Melissa Foster

For more information:

Claudia C. Dobler, MD, PhD, can be reached at cdobler@bond.edu.au; Twitter: @ClaudiaCDobler.

Disclosures: This study was funded by the Agency for Healthcare Research and Quality (AHRQ). Two authors report receiving grants from the AHRQ. All other authors report no relevant financial disclosures.