A Cochrane review [Abstract] 1 included 14 studies with a total of 3 932 subjects. The study duration varied from 3 months to 36 months. Nine studies were of continuous macrolide antibiotics, 2 studies were of intermittent antibiotic prophylaxis (three times per week) and two were of pulsed antibiotic regimens (e.g. five days every eight weeks). The antibiotics investigated were azithromycin, erythromycin, clarithromycin, doxycyline, roxithromycin and moxifloxacin. The mean age of people involved in the trials between 65 and 72 years, and theyd had at least moderate-severity COPD.
With the use of a prophylactic antibiotic, the number of participants experiencing one or more exacerbations was reduced (OR 0.57, 95% CI 0.42 to 0.78; n = 2716; 8 studies) (table T1). This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The frequency of exacerbations per patient per year was also reduced with prophylactic antibiotic treatment (rate ratio 0.67; 95% CI 0.54 to 0.83; n = 1384; 5 studies). The NNT to prevent one patient from exacerbating was 8 (95% CI 5 to 17). There was a statistically significant improvement in quality of life with prophylactic antibiotic treatment as measured by the St George's Respiratory Questionnaire (SGRQ) but this was smaller than the four unit improvement that is regarded as being clinically significant (table T1). Prophylactic antibiotics showed no 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) |
|---|---|---|---|---|
| * Subgroup analysis of continuous versus intermittent versus pulsed antibiotics suggested that pulsed antibiotics were less effective at reducing exacerbations (P = 0.01 for subgroup difference; I2 = 77.3%) **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* | OR 0.57 (0.42 to 0.78) | 606 per 1000 | 468 per 1000(393 to 546) | 2 716(8) |
| Rate of exacerbation per patient/year | Rate ratio 0.67(0.54 to 0.83) | 1 384(5) | ||
| Health-related quality of life, change in SGRQ total score** | The mean change in SGRQ ranged across control groups from0.9 to 5.7 unit decrease | The mean SGRQ (total score) in the intervention groups was1.94 lower (3.13 lower to 0.75 lower) | 2 237(7) | |
| All cause mortality | OR 0.87 (0.66 to 1.15) | 78 per 1000 | 68 per 1000(53 to 88) | 3 309(6) |
| Serious adverse events-continuous or pulsed antibiotics | OR 0.88 (0.74 to 1.05) | 253 per 1000 | 229 per 1000(200 to 262) | 2 978(9) |
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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