COPD exacerbations and Antibiotics

In the current era of antimicrobial stewardship, select use of antibiotics is increasingly important. Physicians are aware of the numerous side effects of antimicrobial therapy, increasing resistance patterns and additional costs associated with prescribing, and hence try to target only those patients who will benefit from these medications because of an underlying infection. Infections are felt to cause up to 75% of all exacerbations, and can be due to bacteria, virus' or additional infectious agents. In 2002, a study in NEJM showed that exacerbations were not only associated with bacterial infections, but with new organisms as opposed to those previously seen in colonization.

Antibiotic therapy in COPD exacerbations has been a controversial topic. Ignoring the early, statistically flawed, small sampled trials from the mid-20th century, Anthonisen et al. performed a RCT in 1987 looking at antibiotics in COPD exacerbation. They categorized patients based on the presence of sputum purulence, increased sputum volume, and increased dyspnea. Patients with all of these characteristics had the largest benefit with antibiotics compared to placebo with an >15% reduction in deteriorations. As the number of criteria reduced, there was less of an effect between the antibiotics (doxy, septra or amox) vs placebo. This is why these three qualifiers have become engrained into our COPDE history and used in the consideration of antimicrobials. The GOLD guidelines recommend antibiotics for exacerbations with sputum purulence with increased volume or dyspnea. The severity of illness also plays a role in considering antimicrobial therapy. A Cochrane Review found that patients admitted to the ICU have a significant benefit from antibiotics therapy, but for inpatients without ICU admission the benefits was not as clear. A retrospective study published in JAMA (2010), examined over 80,000 patients who were hospitalized for COPDE. Failure to receive antibiotics in the first 48 hours was associated with increased mortality, repeated admission and mechanical ventilation.

Use of antibiotics for outpatients has less clinical evidence. There have been randomized trials showing showing decreased duration of symptoms (by days) and longer times until repeat exacerbation with the use of Amox-Clav. However, given the individual risks of harm and mild benefits with antibiotics, utility is questionable. Amox-Clav has been compared to other antibiotics (moxi), without showing any significant difference. Duration of five days may be an appropriate length of treatment in the outpatient setting, where a meta-analysis in COPD showed that five days compared to seven days showed no differences in treatment success and lower adverse events.

Overall, there is no specific antibiotic regiment that should be chosen, and patients should have antimicrobials based on their previous history, local resistance patterns and risk factors for pseudomonas. Whether or not antibiotics should be given at all should be based on an individual basis. I also consider additional clinical factors used in the diagnosis of community acquired pneumonia, such as presence of fever and focal consolidation on chest x-ray.

Anthonisen Annals