Antibiotics and COPD

Situations like the following occur often: A 58 year old woman with history of smoking and COPD presents with increased dyspnea and cough.  She appears exhausted.  She is treated with bronchodilators, steroids, and antibiotics.  But, why antibiotics?  Are most COPD exacerbations associated with bacterial infections?

A randomized placebo controlled trial examining the utility of antibiotics in addition to corticosteroids for acute exacerbation of COPD in a patient population without asthma or pneumonia was published by a Dutch group in 2010. 

Paper: Daniels, J.M.A. et. al., Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.  Am. Journal of Resp. and Crit. Care Med. 181 (2010): 150-157.

Objective: Randomized, placebo controlled trial to test whether addition of doxycycline to corticosteroids improved clinical outcomes.

Setting: Two hospitals in Netherlands

Intervention: Patients in the intervention group received 7 day course of doxycycline while all patients received corticosteroid treatment starting with intravenous steroids for six days followed by slow oral taper in addition to bronchodilators.

Patient Population: Patients were all at least 45 years of age with diagnosed COPD presenting with an acute exacerbation of COPD – described as increased dyspnea, sputum volume, or sputum purulence. Patients were excluded if they were febrile or had radiographic evidence of pneumonia.  265 patients were randomized to get doxycycline (128 patients) or placebo (137 patients).  87% of the doxycycline group completed the trial while 80% of the placebo group completed the trial.  The most common reason for dropout from the trial was perceived lack of efficacy, which was more common in the placebo group.

Outcome Measured: Primary measure was treatment response (either cure or improvement in symptoms) at day 30.  Secondary measures were treatment response at days 10 and cure rates on days 10 and 30.  Other measures tracked were FEV1, CRP, and microbiological response.  Analysis was by intention-to-treat.

Results: At day 30, treatment response was observed in 61% in doxycycline group and 53% in the placebo group, which was not a significant difference (p = 0.32).  The group tracked many secondary outcomes.  At day 10, treatment response was significantly better for the doxycycline group (80%) compared to the placebo group (69%) with p = 0.03.  Regarding clinical cures, there was no difference between the groups at day 30 (51% in doxy group vs. 41% in placebo) while at day 10, more patients in the doxycycline group were cured.   On lung function tests, there was no difference  in FEV1 increases between the two groups in the short term (day 10) or long term (day 30).  Symptomatically, patients with cough or sputum purulence benefited with doxycycline compared to placebo at day 10 but not at day 30.  Microbiologically, the most commonly isolated bacteria were H. influenza (41%), S. pneumoniae (24%), and M. catarrhalis (22%).  In the intervention group, bacterial persistence rates were 31% for H. influenza, 17% for S. pneumoniae, and 9% for M. catarrhalis after completion of doxycycline course.

In subgroup analysis, those patients who did not have all three symptoms of dyspnea, increased sputum, and sputum purulence did not benefit from doxycycline treatment at day 10 or at day 30.

Conclusion: During an acute exacerbation of COPD, treatment with course of antibiotics probably does not make a whole lot of difference in the long term but results in better response rates short term.  At day 10, even with steroids alone, there was an impressive response rate of about 69% compared to 80% response rate with steroids plus doxycycline.  So, the benefit of adding antibiotics is mainly incremental, symptomatic, and experienced mostly by patients with cough and sputum purulence.  In the study, despite doxycycline treatment, there was considerable persistent bacterial colonization not wholly explained by antibiotic resistance (in vitro resistance rate for H. influenza was only 1%).  

So, in our patient presenting with COPD flare with cough and dyspnea without increased sputum or sputum purulence, there is little added benefit in prescribing antibiotics with corticosteroids.  If her cough is particularly bad, she may benefit from the addition of antibiotics.