Macrolides
In older
studies, prophylactic, continuous use of antibiotics had no effect on the
frequency of exacerbations in COPD (Francis et al 1960 & Francis et al.
1961). A study that examined the efficacy of chemoprophylaxis undertaken in
winter months over a 5-year-period concluded that there was no benefit
(Johnston et al. 1969).
However, more
recent studies have shown that regular use of some antibiotics may reduce
exacerbation rate. Therefore, there has been renewed interest in prophylactic
antibiotics for patients with recurrent exacerbations (two or more per year),
resulting in several placebo-controlled trials, with a macrolide being the most
commonly prescribed agent. However, the benefits of antibiotic prophylaxis must
be weighed against concerns about promoting antibiotic resistance and possible
adverse effects. For most patients with COPD, we suggest not administering
antibiotic prophylaxis.
Only
carefully selected patients, such as those who continue to have frequent
exacerbations in spite of optimal therapy for their COPD with bronchodilators
and anti-inflammatory agents, should be considered for antibiotic prophylaxis.
In such patients, we suggest prophylaxis with azithromycin. GOLD 2019 stated
that azithromycin (given at 250 mg daily or at a lower dose of 250-500 mg three
times per week) OR erythromycin (500 mg twice daily) for one year reduced the
risk of exacerbations, compared to usual care (Seemungal et al 2008; Albert et
al 2011 & Uzun et al 2014). UptoDate stated that 250 mg three times per
week was oftenly used to reduce adverse effects, although this dose is less
well studied.
When prophylactic
antibiotics are prescribed, careful attention should be paid to
contraindications, and patients should be closely monitored for adverse
effects. Suspected bacterial exacerbations in patients on antibiotic
prophylaxis should be treated with antibiotics that are from a different class
than the prophylactic agent. Even if the regimen is successful in reducing
exacerbations, interrupting treatment after 48-52 weeks should be considered.
Interventions to prevent exacerbations of COPD that are unrelated to infection
are discussed separately.
Azithromycin
use was associated with an increased incidence of bacterial resistance,
prologation of QTc intervals and impaired hearing tests (Albert et al 2011). Hearing
should be assessed periodically as macrolides were associated with hearing loss
in clinical trials. A post-hoc analysis suggests lesser benefit in active
smokers (Han et al. 2014). There are no data showing efficacy or safety of
chronic azithromycin treatment to prevent COPD exacerbations beyond one year of
treatment.
Moxifloxacin
Although
moxifloxacin has demonstrated efficacy for the prevention of COPD
exacerbations, we generally reserve it for the treatment of serious pulmonary
infections in order to reduce the risk of selecting fluoroquinolone-resistant
bacteria and causing C. difficile infection.
Pulse therapy with moxifloxacin
(400 mg/day for 5 days every 8 weeks) in patients with chronic bronchitis and
frequent exacerbations had no beneficial effect on exacerbation rate overall.
The recommendation is based on the randomised controlled trials conducted by
Sethi et al. (2010), where moxifloxacin is given at 400 mg/day for 5 days every
8 weeks, for six cycles for a total duration of 48 weeks. The study revealed
that:
- The patients who received moxifloxacin were less likely to have a COPD exacerbation in both the per-protocol analysis (OR 0.75, 95% CI 0.565-0.994) and in the intent-to-treat analysis (OR 0.81, 95% CI 0.645-1.008).
- A post-hoc analysis of per-protocol patients with purulent or mucopurulent sputum production at baseline showed a larger benefit with antibiotic prophylaxis (OR 0.55, 95% CI 0.36-0.84).
- Sustained emergence of moxifloxacin-resistant strains was not observed in sputum or in enteric flora.
- Gastrointestinal adverse effects were more frequent with moxifloxacin; however, C. difficile infections were not observed.
References:
2. UptoDate: Management of refractory chronic obstructive pulmonary disease
3. Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD), 2019. Pocket Guide to COPD Diagnosis, Management, and Prevention: A Guide for Health Care Professionals.
4. Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD), 2019. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease.
All information accessed on 19 Sept 2019