A Cochrane review included 7 studies with a total of 3 170 subjects. The study duration varied from 3 months to 36 months. Five studies were of continuous antibiotics and 2 studies were of intermittent antibiotic prophylaxis. The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. The five studies of continuous prophylactic antibiotics used macrolides, whereas of the 2 pulsed antibiotic studies one used a quinolone (moxifloxacin) for 5 days every 8 weeks, for a total of 6 courses, and the other used azithromycin 500 mg daily for 3 days every month for 3 years. On average, the people involved in the trials were 66 years old and had either moderate or severe COPD.
With the continuous use of a prophylactic macrolide antibiotic, there was a significant reduction in the number of patients with exacerbations (table ), the rate of exacerbations per patient per year (rate ratio 0.73, 95% CI 0.58 to 0.91), and the median time to the first exacerbation compared to placebo treatment. The NNT to prevent one patient from exacerbating was 8 (95% CI 5 to 18). Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (table ), and the test for interaction showed that this result was significantly different from the effect on exacerbations with continuous antibiotics. There was a statistically significant improvement in quality of life with both continuous and pulsed antibiotic treatment but this was smaller than the four unit improvement that is regarded as being clinically significant (table ). Neither pulsed nor continuous antibiotics showed a significant effect on the secondary outcomes of frequency of hospital admissions, change in lung function, serious adverse events or all-cause mortality.
| Outcome | Relative effect (95% CI) | Control | Antibiotic | Participants (studies) |
|---|---|---|---|---|
| * St George's Respiratory Questionnaire (SGRQ): scale from 0 to 100. SGRQ comprises of responses to 50 items, 0 being the best possible score and 100 the worst. | ||||
| Number of people with one or more exacerbations -continuous or pulsed antibiotics | OR 0.64 (0.45 to 0.9) | 60 per 100 | 49 per 100 (41 to 58) | 2 411 (4) |
| Number of people with one or more exacerbations -continuous antibiotics | OR 0.55 (0.39 to 0.77) | 69 per 100 | 55 per 100 (46 to 63) | 1 262 (3) |
| Number of people with one or more exacerbations -pulsed antibiotics | OR 0.87 (0.69 to 1.09) | 51 per 100 | 47 per 100 (42 to 53) | 1 149 (1) |
| Health-related quality of life, change in SGRQ total score* -continuos or pulsed antibiotics | The mean change in SGRQ ranged across control groups from -0.6 to -2.8 units | The mean SGRQ (total score) in the intervention groups was 1.78 better (2.95 to 0.61 better) | 1 962 (3) | |
| All cause mortality -continuous or pulsed antibiotics | OR 0.89 (0.67 to 1.19) | 83 per 1000 | 74 per 1000 (57 to 97) | 2 841 (3) |
| Serious adverse events -continuous or pulsed antibiotics | OR 0.88 (0.73 to 1.07) | 267 per 1000 | 243 per 1000 (210 to 281) | 2 411 (4) |
The adverse events that were recorded varied among the trials depending on the different antibiotics used. Azithromycin was associated with a significant hearing loss in the treatment group. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.
The development of antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment.
Consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse. If an informed decision is made to start prophylactic antibiotics in a particular patient, there needs to be baseline checks to confirm the identity of the infection (for example sputum cultures) and ECG or audiometry, depending on the planned antibiotic, as well as ongoing monitoring of the same.
The benefit in prevention of exacerbations was seen in patients which had at least moderately severe COPD and were already frequent exacerbators needing treatment with antibiotics or systemic steroids or who were on supplemental oxygen.
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