Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD)

Article (PDF Available)inCochrane database of systematic reviews (Online) 11(11):CD009764 · November 2013with275 Reads
DOI: 10.1002/14651858.CD009764.pub2 · Source: PubMed
There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). To determine whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality). This represented a reduction from 69% of participants in the control group compared to 54% in the treatment group (95% CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb) was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58 to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study, 1149 participants, moderate quality) 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 (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants, moderate quality).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 (moderate quality evidence).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. Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All trials of continuous antibiotics used macrolides hence the noted benefit applies only to the use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains uncertain and requires further research.The trials in this review included patients who were frequent exacerbators and needed treatment with antibiotics or systemic steroids, or who were on supplemental oxygen. There were also older individuals with a mean age of 66 years. The results of these trials apply only to the group of patients who were studied in these trials and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, 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.

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Available from: Samantha Chandani Herath
    • "The continuous use of antibiotics may raise a concern about bacterial resistance, and an increase in respiratory pathogens resistant to macrolides has been identified with this approach in patients with COPD [108]. Long-term use of macrolides has also been linked to hearing loss and gastrointestinal events [106]. Thus, this approach may be best for patients who experience frequent bacterial exacerbations despite optimal treatment with bronchodilators and anti-inflammatory agents [109] and it may be prudent to limit their use to reference centers with adequate follow- up [59] . "
    [Show abstract] [Hide abstract] ABSTRACT: Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan. Electronic supplementary material The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users.
    Full-text · Article · Sep 2016
    • "This is a clinically useful measure of the effect of treatment as described by Cook et al. [18]. For comparison, as demonstrated by Herath et al., the NNT with use of continuous prophylactic antibiotics to avoid an exacerbation of chronic obstructive pulmonary disease is 8 [19]. As shown in the data presented by Rimouche et al., morbidity can also be reduced by implementing surgical techniques such as transverse incision, preservation of the long saphenous vein and Sartorius switch. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Inguinal lymph node dissection (ILND) is associated with a high rate of morbidity. To evaluate the clinical benefit of surgical adhesives to reduce complications in patients undergoing ILND, we compared the use of TissuGlu(®) Surgical Adhesive and ARTISS(®) fibrin sealant with a control population. Material and methods: We conducted a retrospective analysis of patients undergoing ILND for metastatic malignant skin tumors at one hospital, Fachklinik Hornheide (Münster, Germany), from January 2011 through September 2013, assessing 137 patients with a total of 142 procedures. Results: Complications occurred in 22/60 procedures in the TissuGlu group (TG), in 8/17 in the ARTISS group (AG), and in 29/65 in the control group (CG). Prolonged drainage and seroma were recorded in 16 (26.7%), four (23.5%), and 26 (40%) respectively (non-significant). TG showed less extended drainage vs. CG (p=0.082). Mean daily drain volumes were significantly lower in AG vs. CG (p=0.000). With regard to wound infection, there was a 15% reduction in TG and 74% increase in AG group. Revision surgery was reduced by 36% in TG and increased by 54% in AG. Mean daily drain volumes were significantly lower in AG vs. CG (p=0.000). Mean total post-operative drain volume was lower in TG and AG vs. CG (p<0.001 among groups, CG vs. TG p<0.001, CG vs. AG p<0.001). The mean body mass index (BMI) was significantly higher in patients with complications, 29.4±5.8 vs. 25.3±4.1 (p=0.000). Conclusion: The use of TissuGlu in our ILND patients was associated with a reduction in post-operative wound related complications and the need for revision surgeries compared to the control group. Daily drainage was significantly lower within the first 7 post-operative days with the use of ARTISS, but the benefit was lost due to the higher occurrence of wound infection and revision surgery. BMI above 29 is a risk factor for complications following ILND. (Level of evidence: level IV, retrospective case study).
    Full-text · Article · Jan 2016
    • "Only macrolides were used in the continuous regimens-namely azithromycin, erythromycin and clarithromycin. The authors found statistically significant reduction in the number of exacerbations, odds ratio 0.55, number needed to treat avoid one exacerbation was 8 [33] 3. "
    Article · Jan 2016 · Respiratory research
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