Now, in preparing this talk, I went back and looked at some of the guidelines published over the past 20 years or so, many of them are well known, and I’ll point out that GOLD initiative has a 2022 publication, the European Respiratory Society, the American Thoracic Society have something that’s a little older from 2017. But they’ve changed somewhat from their original approach 20 years ago and in their latest guidelines, they take an approach to using antibiotics and then deciding which ones based on local susceptibility. So, GOLD points out that if the patient has non-purulent sputum, a low C-reactive protein, no antibiotic is indicated; if you have the three cardinal symptoms, or especially if you have two of them including purulent sputum – you should use antibiotics based on the local susceptibilities. According to the European Respiratory Society, you probably should use antibiotics in ambulatory patients with an exacerbation based on local susceptibility. So, what I found was one of the newer online publications, which is high quality, it’s called ‘Up to Date’ – it’s by subscription, the information is frequently available through medical libraries, or hospitals. And this is written by experts, peer-reviewed and updated every three or four months, and they suggest that for a moderate AECOPD exacerbation without likelihood of penicillin-resistant pneumonia or pseudomonas – a macrolide or a second-generation cephalosporin should be considered; trimethyl sulfa as a second choice, and they feel doxycycline has lost enough coverage that it should not be used. For moderately severe cases, again without resistant organisms – the recommendations are amoxicillin clavulanate, or respiratory fluoroquinolones with moxifloxacin not recommended because of its diminished gram-negative coverage compared to levofloxacin and ciprofloxacin. For moderate to severe cases with significant penicillin-resistant pneumococcal or Pseudomonas – respiratory fluoroquinolones is the choice. The British actually put in combination with an amoxicillin agent for some of the respiratory pathogens. Again, this is reflected somewhat in the Spanish guidelines for 2021 – they recommend respiratory fluoroquinolones or if Pseudomonas is present in anti-Pseudomonas or beta lactam, which generally means an intravenous agent or a respiratory fluoroquinolones. The National Institute for Health and Care Excellence (NICE) in the UK starts with amoxicillin or doxycycline or clarithromycin, but again reaches the same place with respiratory fluoroquinolones.
Now when you compare non-fluoroquinolone antibiotics with fluoroquinolones for AECOPD, there’s some important differences to keep in mind. Non-fluoroquinolones may be narrower in spectrum. This can be helpful in preventing overgrowth of yeast, or C.difficile. The cost of some of the non-specific agents like amoxicillin is less than fluoroquinolones. On the other hand, significant numbers of patients will complain of penicillin, amoxicillin, or sulfa allergies. Specific toxicities for example, the risk of renal failure with agents such as sulfa drugs in the elderly patient may be a contraindication to its use. And finally, most non-fluoroquinolone antibiotics, particularly oral ones do not cover Mycobacterium tuberculosis (TB). This is in fact an advantage because in areas with a high endemic TB rate, if TB is the differential diagnosis, non-fluoroquinolones are unlikely to mask a TB infection, whereas fluoroquinolones might delay the presentation of TB. The fluoroquinolones, however, are very convenient. Levofloxacin for example, is once a day and a variety of doses. They’re generally well tolerated, though there are specific toxicities to keep in mind. For example, tendinitis with fluoroquinolones, they cover many antibiotic resistant AECOPD pathogens as we’ve discussed; and the pharmacokinetics i.e., the ability to achieve a very high tissue and lung level with a single dose is very helpful in being effective and decreasing the number of organisms present in the lungs, and this may translate to a longer period before relapse of infection. Recommendations for fluoroquinolones – avoid any antimicrobial agent in mild AECOPD unless you suspect infection, for example, fever, no local antibiotic susceptibility patterns, both for your area, your institution and your patient. Consider the fluoroquinolones in an at-risk patient – these are the ones who are becoming severely ill, and also considered their risk factors who are resistant to organisms, such as prior antibiotics, hospitalization, or known colonization. Educate the patient and family about the use of COPD drugs including antibiotics. And if tuberculosis is in the differential diagnosis, either send cultures for MTB or watch the patient more carefully for evaluation for TB if they’re worsening.
And this just shows some older data, which indicates that when penicillin, macrolides or cephalosporins are used to treat AECOPD, the average days to relapse is about 2-2.5 weeks; fluoroquinolones are somewhat longer, 26 days. Again, the important thing is to get the patient better and get them to follow a good maintenance regimen of broncho dilators, and so forth.