Again, going back about 20 years where some of this Foundation was established – the European Respiratory Society and the American Thoracic Society published a suggested approach to treating the COPD patient. It includes patient and family education, about use of inhalers. There’s been a lot of interest and publications about bhronco dilators, the best ones to use and the sequence as well as corticosteroids. What are the indications for corticosteroids to control inflammation and COPD. And finally, as far back as 20 years ago, antibiotics were recognised and sputum characteristics are one of the things that were used to determine when antibiotics were needed. It was always stated that the choice of antibiotics depended on local susceptibility patterns and the patient’s individual cultures. But the choices in simpler times were Amoxicillin, Ampicillin or Cephalosporins, Doxycycline and Tetracycline derivative, macrolides such as Azithromycin were used. And then for patients who had prior antibiotic therapy, Amoxicillin clavulanate, and respiratory Fluoroquinolones, which have broader activity were suggested.

Now this is actually from a generation ago, Anthonissen was well known for studying exacerbations of COPD – he defined an exacerbation with three different parameters shortness of breath, sputum volume, and sputum purulence. And in his study he found that when only one of these parameters was present, it didn’t matter whether you gave a patient an antibiotic or placebo; their recovery over time was about the same. When they had two out of three parameters suggesting exacerbation, there was a difference with somewhat more patients improving on antibiotic but not a statistically significant difference. And finally, in the patients with all three, and some people, particularly in the protocols have suggested that sputum purulence may be the key factor. When all three of these parameters for an exacerbation were present; there was a statistically significant rate of improvement with antibiotics compared to placebo, though it was relatively small. So, studies have been ongoing trying to define which antibiotics are the most helpful.

Now again, turning to pathogens many of these pathogens have developed increasing resistance which we’ll use to examine which antibiotics should be chosen. Streptococcus pneumonia, the Pneumococcus over the past generation or two really since the 1960s, has developed considerable resistance to penicillin, including amoxicillin and even the Macrolides. There’s been increasing resistant to Cephalosporins and amoxicillin clavulanate which is not beta-lactamase mediated, but rather due to changes in penicillin binding proteins and selection for higher MICs. Haemophilus influenza many times is significantly resistant to amoxicillin. This depends on location and I think our British Colleagues are still fans of ampicillin, amoxicillin, IV ampicillin, and it may also be susceptible to trimethoprim-sulfa though less so than in the past. Enteric gram-negatives and using Klebsiella as example, have become potentially multi-drug resistant. This is especially true in nosocomial infections and in all sites, catheter-related bloodstream intra-abdominal and respiratory; and many Klebsiella produce extended spectrum beta-lactamase, some produce carbapenemnases which are very destructive to beta-lactam antibiotics and make them more difficult to treat. Pseudomonas aeruginosa has also been involved in increasing resistance, and now be maybe fluoroquinolone resistant or multi drug resistant – this is why it’s important to know your local susceptibility patterns and obtain patterns on patients that you’ve decided to treat and have the potential for developing severe respiratory failure.

Now, again, going back to which antibiotics to treat for an exacerbation of COPD, the local susceptibility patterns are important, these change over time. So, it’s probably important to know national guidelines for COPD with local guidelines for antibiotic resistance. When you treat empirically, you like activity against a broad range of pathogens so that you’re likely to treat the ones that are causing the patient’s exacerbation. It’s also important to stratify the therapy according to the patient. If the patient is severely ill, they require hospitalization, they may require intubation. These are patients in whom you will consider broader spectrum antibiotics, even multiple antibiotic therapy. And remember, we’re not only trying to improve the outcome of that single exacerbation, but also increase the disease-free interval so patients are not always coming back into the clinic or being readmitted to the hospital and have a better quality of life.