Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD)
ABSTRACT 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.
Full-textDOI: · Available from: Samantha Chandani Herath, Aug 13, 2015
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ABSTRACT: PurposeWe aimed to determine the incidence and the prognostic impact (mortality and length of ICU stay (LOS)) of pulmonary embolism (PE) in critically-ill patients with severe acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods This is a retrospective study performed during a 5-year period in the intensive care unit of the Habib Bourguiba university hospital (Sfax-Tunisia). All patients with severe acute exacerbation of COPD were included. The diagnosis of PE is confirmed by spiral computed tomography (CT) scan showing one or more filling defects or obstruction in the pulmonary artery or its branches. ResultsDuring the study's period, 131 patients with acute exacerbation of COPD were admitted in our ICU. The mean age (± SD) was 68.6 ± 9.2 years ranging from 39 to 99 years (median: 70 years). During their ICU stay, 23 patients (17.5%) developed PE. The diagnosis was confirmed within 48 hours from ICU admission in all cases but one. The comparison between the two groups (with and without PE) showed that they had the same base line characteristics. However, all PE group developed shock on ICU admission or during ICU stay. Signs of right heart failure were more observed in the PE group. ICU mortality was significantly higher in the PE group (69.5 % Vs 44 %; p= 0.029). In addition the ICU LOS was significantly higher in the PE group than the PE free group (p= 0.007). Finally PE was identified as an independent factor predicting poor outcome (OR= 3.49, CI95% [1.01-11.1; p = 0,035). Conclusion Our study showed that PE is common in patients with severe COPD exacerbation requiring ICU admission. Moreover, PE was significantly associated with higher mortality and ICU LOS in critically-ill patients with severe COPD exacerbation.The Clinical Respiratory Journal 03/2014; 9(3). DOI:10.1111/crj.12131 · 2.20 Impact Factor
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ABSTRACT: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Disease severity evaluation was based on airflow limitation for many years. However, it is now obvious that no single parameter can describe the complexity of COPD and a more holistic approach should be utilized. For this reason, newer classifications of the disease are based on multiple clinical characteristics or biomarkers that can predict different clinically meaningful outcomes, such as symptoms, frequency of exacerbations, progression of disease, response to different medications and mortality. Ongoing research highlights such biomarkers, while guidelines have already incorporated them, as the basis of clinical phenotypes. GOLD highlights the need for more intensive treatment of frequent exacerbators and COPD patients whose disease significantly burdens their quality of life. Moreover, a COPD-asthma overlap syndrome with a different prognosis and potentially different therapeutic approach is also recognized. Spanish guidelines also group frequent exacerbators to predominantly emphysematic versus predominantly bronchitic. Another approach aims to create scoring systems, or multidimensional indices, based on multiple biomarkers which evaluate different aspects of the disease. The recognition of all these prognostic and therapeutic patient subgroups lead to a more personalized approach to each patient and also provides data to the –omics to uncover the pathogenetic background of this diversity and develop new targeted treatments.Current Respiratory Medicine Reviews 07/2014; 9(6):372-378. DOI:10.2174/1573398X10666140527000115
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