Time to Reconsider Macrolide Monotherapy

Author: Charles B. Hartley II, MD

In the past, advanced macrolide monotherapy (azithromycin and clarithromycin) was recommended for outpatient treatment of CAP and COPD AE with acute bronchitis. I'm starting to question if this is consistent with best practice.


Macrolide Resistance in the Southeast

Macrolide resistance rates in the SE us exceed 50%; we should avoid macrolides when local resistance is >25%.

The US has one of the highest rates of S. pneumoniae macrolide resistance in the developed world - approximating 40% nationwide. The southeast region of the US has the highest national resistance rate - exceeding 50%! Currently, best practice recommendations advise against advanced macrolide monotherapy for treatment of CAP, acute bacterial bronchitis and infectious COPD exacerbations when local macrolide resistance is greater than just 25%.


So what can we use?


S. pneumoniae remains the most common etiologic source of bacterial CAP in the US. Doxycycline is the preferred agent for patients with CAP who: do not have medical comorbidities, are to be treated as outpatients, are not pregnant and are not known to be doxycycline intolerant. Doxycycline has been demonstrated to be clinically effective against S. pneumoniae, H. influenzae, Moraxella, Legionella, Mycoplasma, and Chlamydia strains. In the US, more than 80% of clinically relevant S. pneumoniae strains are doxycycline sensitive with comparable demonstrated clinical efficacy.


What about patients with CAP who are to be treated as an outpatient who ARE Doxycycline intolerant, pregnant or with major medical comorbidities (COPD, chronic liver or renal disease, cancer, diabetes, alcoholism ,CHF, and primary or secondary immunosuppression, etc)?  Current recommendations for treatment include either a beta lactam/macrolide combination or respiratory quinolone monotherapy (usually levofloxacin or moxifloxacin).


The convenience of monotherapy with a quinolone must be balanced against the increased risk of selecting drug resistant organisms and development of C. difficile (much higher risk when using quinolones). If patient is intolerant or with some other contraindication to macrolides, a beta lactam (acceptable choices include augmentin, cefuroxime, and cefdinir) + doxycycline combination is recommended.


What About Our Patients Hospitalized for COPD + Bronchitis?

For patients with severe COPD AE and bronchitis (and by definition patients with disease significant enough to warrant hospitalization), antibiotic choice recommendations are often stratified based on the presence of risk factors for Pseudomonas. In patients without risk factors for Pseudomonas, UpToDate recommends levofloxacin, ceftriaxone, or cefotaxime monotherapy. GOLD 2017 recommendations are less specific. For those with risk factors for Pseudomonas (previous sputum isolation of Pseudomonas, concomitant bronchiectasis, frequent systemic steroid administration, frequent usage of antibiotics, frequent/recent hospitalizations and advanced COPD) recommended choices include levofloxacin, cefepime, piperacillin-tazobactam, or ceftazidime.  

Outpatient Rx

Non pregnant

No comorbidities

Doxy tolerant

Outpatient Rx


+ comorbidities

Doxy intolerant

COPD AE + Bronchitis, no pseudomonal risk factors

COPD AE + Bronchitis WITH pseudomonal risk factors


Beta Lactam


Macrolide OR Doxycycline




Respiratory quinolone monotherapy


























What now?

There are many antibiotics to choose from for the outpatient treatment of CAP, acute bacterial bronchitis and COPD AE + bronchitis. Macrolide monotherapy simply isn't one of them - at least not for the bugs in our local antibiogram.