≥ 4 exacerbations/year and at least 2 of following criteria:

Ciprofloxacin has poor/no coverage of S. pneumoniae and should not be used routinely in AECB. Because it retains the best activity against Pseudomonas aeruginosa, ciprofloxacin may have a role in end stage disease with/without bronchiectasis, when there has been documentation of colonization/infection with this organism. Empiric S. pneumoniae coverage still recommended.
Levofloxacin has good coverage of the pathogens involved. However because of its broad spectrum, potential for increasing resistance, risk of Clostridioides difficile infection, and significant adverse effect profile, it should be reserved for amoxicillin and cefuroxime allergic patients or patients who have failed first line antibiotic therapy.

These agents have poor Haemophilus coverage and significant S. pneumoniae resistance. The benefit of macrolides may be due more to their anti-inflammatory activity than their antibacterial activity.
Long term macrolide therapy cannot be recommended at this time given its marginal benefit in only select groups of COPD patients, unacceptably high potential for drug interactions & adverse effects, and proven significant risk of development of antibiotic resistance.

Usual Pathogens

Haemophilus spp
S. pneumoniae
Moraxella catarrhalis
Enterobacterales
Pseudomonas spp