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. 2019 May 24;5(5):CD013024.
doi: 10.1002/14651858.CD013024.pub2.

Head-to-head oral prophylactic antibiotic therapy for chronic obstructive pulmonary disease

Christopher Jd Threapleton  1 , Sadia Janjua, Rebecca Fortescue, Emma H Baker
Affiliations

Head-to-head oral prophylactic antibiotic therapy for chronic obstructive pulmonary disease

Christopher Jd Threapleton et al. Cochrane Database Syst Rev. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD; including chronic bronchitis and emphysema) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. Long-term antibiotic use may reduce both bacterial load and inflammation in the airways. Studies have shown a reduction of exacerbations with antibiotics in comparison to placebo in people with COPD, but there are concerns about antibiotic resistance and safety.

Objectives: To compare the safety and efficacy of different classes of antibiotics (continuous, intermittent or pulsed) for prophylaxis of exacerbations in patients with COPD.

Search methods: We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was conducted on 6 February 2019.

Selection criteria: Randomised controlled trials (RCTs) were selected that compared one prophylactic antibiotic with another in patients with COPD.

Data collection and analysis: We used the standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data and assessed risk of bias. Discrepancies were resolved by involving a third review author.

Main results: We included two RCTs, both published in 2015 involving a total of 391 participants with treatment duration of 12 to 13 weeks. One RCT compared a quinolone (moxifloxacin pulsed, for 5 days every 4 weeks), with a tetracycline (doxycycline continuous) or a macrolide (azithromycin intermittent).The second RCT compared a tetracycline (doxycycline continuous) plus a macrolide (roxithromycin continuous), with roxithromycin (continuous) alone.The trials recruited participants with a mean age of 68 years, with moderate-severity COPD. Both trials included participants who had between two and five exacerbations in the previous one to two years. In one trial, 17% of patients had previously been using inhaled corticosteroids. In the other study, all patients were positive for Chlamydophila pneumoniae (C pneumoniae).Overall, we judged the evidence presented to be of very low-certainty, mainly due to imprecision, but we also had concerns about indirectness and methodological quality of the included studies. The primary outcome measures for this review included exacerbations, quality of life, drug resistance and serious adverse events.Macrolide + tetracycline versus macrolide There was no clear difference between treatments in improvement in quality of life as assessed by the Chronic Respiratory Questionnaire (CRQ). The CRQ scale ranges from 0 to 10 and higher scores on the scale indicate better quality of life. CRQ sub-scales for dyspnoea (mean difference (MD) 0.58, 95% confidence interval (CI) -0.84 to 2.00; 187 participants; very low-certainty evidence), fatigue (MD 0.02, 95% CI -1.08 to 1.12; 187 participants; very low-certainty evidence), emotional function (MD -0.37, 95% CI -1.74 to 1.00; 187 participants; very low-certainty evidence), or mastery (MD -0.79, 95% CI -1.86 to 0.28; 187 participants; very low-certainty evidence) at 12 weeks. For serious adverse events, it was uncertain if there was a difference between combined roxithromycin and doxycycline versus roxithromycin alone at 48 weeks follow-up after active treatment of 12 weeks (odds ratio (OR) 1.00, 95% CI 0.52 to 1.93; 198 participants; very low-certainty evidence). There were five deaths reported in the combined treatment arm, versus three in the single treatment arm at 48 weeks follow-up after active treatment of 12 weeks (OR 1.63, 95% CI 0.38 to 7.02; 198 participants; very low-certainty evidence).Quinolone versus tetracycline There was no clear difference between moxifloxacin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants, very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.Quinolone versus macrolide There was no clear difference between moxifloxacin and azithromycin for the number of participants experiencing one or more exacerbations (OR 1.00, 95% CI 0.32 to 3.10; 50 participants; very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.Marcolide versus tetracycline There was no clear difference between azithromycin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants; very low-certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes.We did not find head-to-head evidence for impact of antibiotics on drug resistance.

Authors' conclusions: It is not clear from the evidence included in this review whether there is a difference in efficacy or safety between different classes or regimens of prophylactic antibiotic, given for 12 to 13 weeks to people with COPD. Whilst no head-to-head comparisons of antibiotic resistance were identified, concerns about this continue. The sample size in this review is small and both included studies are of short duration. Thus, there is considerable uncertainty in effects observed and the effects of different prophylactic antibiotics requires further research.

PubMed Disclaimer

Conflict of interest statement

CT is employed part‐time by a NIHR Programme Grant to complete work on this review and is a clinical fellow in pharmacology.

SJ is employed full‐time as a systematic reviewer by a NIHR Programme Grant to complete work on this review.

RF is employed part‐time by a NIHR Programme Grant to complete work on this review and is a qualified general practitioner.

EB is a consultant clinical pharmacologist.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 1 Mean time to first exacerbation (days).
1.2
1.2. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 2 CRQ quality of life; change; endpoint 12 weeks.
1.3
1.3. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 3 CRQ quality of life; change; endpoint 60 weeks.
1.4
1.4. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 4 All‐cause serious adverse events; endpoint 60 weeks.
1.5
1.5. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 5 Treatment‐related serious adverse events; endpoint 60 weeks.
1.6
1.6. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 6 Lung function (FEV1 trough); change; endpoint 12 weeks.
1.7
1.7. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 7 Lung function (FVC); change; endpoint 12 weeks.
1.8
1.8. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 8 All‐cause mortality; endpoint 60 weeks.
1.9
1.9. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 9 All‐cause adverse events; endpoint 60 weeks.
1.10
1.10. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 10 Treatment‐related adverse events; endpoint 60 weeks.
1.11
1.11. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 11 Lung function (FEV1 % predicted); change; endpoint 60 weeks.
1.12
1.12. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 12 Lung function (FEV1 trough); change; endpoint 60 weeks.
1.13
1.13. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 13 Lung function (FEV1 % predicted); change; endpoint 12 weeks.
1.14
1.14. Analysis
Comparison 1 Macrolide+tetracycline versus macrolide, Outcome 14 Lung function (FVC); change; endpoint 60 weeks.
2.1
2.1. Analysis
Comparison 2 Quinolone versus tetracycline, Outcome 1 Number of people with one or more exacerbations.
3.1
3.1. Analysis
Comparison 3 Quinolone versus macrolide, Outcome 1 Number of people with one or more exacerbations.
4.1
4.1. Analysis
Comparison 4 Macrolide versus tetracycline, Outcome 1 Number of people with one or more exacerbations.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013024

References

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