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Long Term Antibiotic Treatment For Copd

Effects On Cytokines And Inflammatory Mediators

Long-term impact of COPD acute exacerbations

shows the macrolide class of antibiotics to be the most effective at inhibiting pro-inflammatory interleukins , chemokines , and other inflammatory cytokines . Azithromycin shows the most convincing evidence in support of anti-inflammatory properties: it was found to reduce levels of every inflammatory molecule it was tested on, across a range of study types. This included inhibiting IL-10 and IL-12, which none of the other antibiotics were shown to reduce. Clarithromycin and roxithromycin were both shown to have very similar immunomodulatory properties, so they may also be effective anti-inflammatory agents. In contrast, erythromycin did not affect cytokine or chemokine release.

Summary of Modulatory Effects of Antibiotics in COPD

Data Extraction And Outcomes Of Interest

Data from the included studies were extracted independently by two of the authors . Any disagreement was resolved by the adjudicating senior author , and a final consensus was reached among all the authors. We extracted the first author, year of publication, country, study design, sample size, population characteristics, antimicrobial agent, dose administered, duration of the treatment, and information on outcome measures. The primary outcomes were the total number of patients with one or more exacerbations and the rate of exacerbations per patient per year. The secondary outcomes were the number of patients requiring hospitalization, health-related quality of life based on the St George Respiratory Questionnaire score, and the total number of patients who experienced adverse events.

Conflict Of Interest Statement

  • Roede BM, Bindels PJ, Brouwer HJ, Bresser P, de Borgie CA, Prins JM. Antibiotics and steroids for exacerbations of COPD in primary care: compliance with Dutch guidelines. Br J Gen Pract . 2006 Sep 56:6625.
  • Bathoorn E, Groenhof F, Hendrix R, van der Molen T, Sinha B, Kerstjens HA, et al. Real-life data on antibiotic prescription and sputum culture diagnostics in acute exacerbations of COPD in primary care. Int J Chron Obstruct Pulmon Dis . 2017 12:28590.
  • Roede BM, Bresser P, Bindels PJE, Kok A, Prins M, ter Riet G, et al. Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study. Thorax . 2008 Nov 63:96873.
  • Roede BM, Bresser P, Prins JM, Schellevis F, Verheij TJ, Bindels PJ. Reduced risk of next exacerbation and mortality associated with antibiotic use in COPD. Eur Respir J
  • Sachs APE, Koeter GH, Groenier KH, Vanderwaaij D, Schiphuis J, Meyboomdejong B. Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary-disease in general-practice. Thorax . 1995 Jul 50:75863.
  • Jorgensen AF, Coolidge J, Pedersen PA, Petersen KP, Waldorff S, Widding E. Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis. A double-blind, placebo-controlled multicentre study in general practice. Scand J Prim Health Care . 1992 Mar 10:711.
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    Characteristics Of Eligible Studies

    The characteristics of included studies are shown in Table 1. These studies, published between 2001 and 2018, were mostly conducted in UK. The study population, with ages generally ranging from 65 to 73 years, included more men than women. Most of the patients had moderate-to-severe COPD diagnosed by current spirometric criteria, with mean FEV1 of 33.9%56.5% of the predicted value. A total of 1,078 patients were allocated to the macrolide treatment group , and 1,023 were allocated to the control group. The duration of macrolide therapy was more than 3 months but less than 1 year. Evaluation suggested that the quality of the enrolled RCTs was ideal , and the retrospective study also received seven stars .

    Graph of the bias risk of the enrolled RCTs.

    Note: The other bias refers to intention-to-treat analysis.

    Abbreviation: RCT, randomized controlled trail.

    Study Outcomes And Definitions

    Areas of controversy about long

    The primary outcome was to compare 30-day all-cause hospital readmissions between patients who received 24 hours of antibiotics and those who received > 24 hours of antibiotics for their AECOPD.

    Secondary outcomes included the duration of antibiotic treatment, corticosteroid use, duration of inpatient LOS, COPD-related readmission within 30 days of discharge, and 30-day mortality. In addition to comparing all patients who received 24 hours of antibiotics to those who received > 24 hours of antibiotics, we compared all outcomes among patients who received 24 hours of azithromycin to those who received > 24 hours of azithromycin.

    To identify risk factors for hospital readmissions, we performed univariate analysis and planned to perform multivariate analysis. Variables with a P value < .20 on univariate analysis would be included in the multivariate analysis.

    Antibiotic treatment duration included both inpatient antibiotics administered and outpatient antibiotics prescribed. Corticosteroid use was standardized to prednisone equivalents. For purposes of this study, corticosteroid prescribing beyond 30 days of discharge was not collected.

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    Why It Is Important To Do This Review

    This review incorporates and builds upon earlier Cochrane reviews.The most recent review concluded that the “use of continuous prophylactic macrolide antibiotics for a period of up to 12 months is likely to reduce the number of patients with exacerbations and exacerbation frequency, increase the median time to first exacerbation and possibly healthrelated quality of life” . However, adverse effects and the potential for the development of antibiotic resistance remain a concern. Since the 2013 review, a number of new studies into prophylactic antibiotic use in COPD have been published. Given the fine balance between the need to reduce exacerbation frequency in COPD, with the threat of widespread antibiotic resistance, it is important that the most uptodate research is incorporated into this review, so that physicians and patients can make well informed decisions before embarking on longterm treatment. This updated review also expands on the analysis of specific prophylactic antibiotic regimens including continuous, intermittent, and pulsed regimens to determine their relative efficacy and safety. Furthermore, many of the new studies have included more comprehensive assessments of quality of life indicators, which were not previously explored in great detail.

    Data Collection And Covariates

    Age was calculated based on the date of birth and the index date. On the enrollment date, the following information was extracted as covariates from the Lifelines cohort Biobank to describe the characteristics of cohort members with AECOPD: smoking history, GOLD stages of COPD, lung function parameters, and related comorbidities including cardiovascular diseases, diabetes, depression, and other disorders. If information concerning the chronic risk status of AECOPD was not documented on the enrollment date, we used information from the closest follow-up assessment in the Lifelines, if available. Additionally, information on gender, the frequency of AECOPD, and maintenance drugs for COPD in the previous year before the index date was retrieved from the database.

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    Review Of The Guideline

    This guideline topic was chosen to inform practice in a growing clinical area, but also to act as a pilot for the use of GRADE methodology for all future BTS guidelines. The GDG recognise that the topic area would include a range of diseases with differing levels of evidence and thus act as a useful learning exercise for the introduction of GRADE methodology. It is not proposed to update this guideline as a distinct entitythe intention is for macrolide use to be encompassed in future disease-specific guideline updates.

    Results Of Network Meta

    Consequences to Long-Term Antibiotic Therapy

    In the network meta-analysis, the eligible comparisons of clinical cure rates are presented in Fig. , which are predominantly pairwise comparisons of different drug treatments for AECOPD. The figure weighs the nodes according to the number of studies that evaluated each treatment the edges are weighed according to the precision of the direct estimate, and the edges are coloured based on the average bias level for each pairwise comparison with respect to double-blinding. Of all the comparisons, only azithromycin was directly compared with 5 other active drugs. Amoxicillin-clavulanic acid and ciprofloxacin were directly compared with 4 other drugs including a placebo. For tolerability, the eligible comparisons of adverse effects are presented in Fig. . Only placebo was directly compared with 5 other active drugs, and amoxicillin-clavulanic acid was directly compared with 4 other drugs including placebo.

    Fig. 3

    The league table of the network for clinical cure rate assesses the treatments according to their relative effects and is shown in Additional file : Table S1. In terms of efficacy, ofloxacin was significantly better than both doxycycline and placebo . Results for the adverse effects are shown in Additional file : Table S2. Dirithromycin was significantly better than moxifloxacin , prulifloxacin , sparfloxacin , and zabofloxacin . Placebo was significantly better than moxifloxacin .

    Fig. 5

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    Copd: Management Of Acute Exacerbations And Chronic Stable Disease

    MELISSA H. HUNTER, M.D., and DANA E. KING, M.D., Medical University of South Carolina College of Medicine, Charleston, South Carolina

    Am Fam Physician. 2001 Aug 15 64:603-613.

    See patient information handout on chronic obstructive pulmonary disease, written by the authors of this article.

    Despite public education about the dangers of smoking, chronic obstructive pulmonary disease continues to be a major medical problem and is now the fourth leading cause of death in the United States.1 Approximately 20 percent of adult Americans have COPD.2 Acute bronchitis and acute exacerbations of COPD are among the most common illnesses encountered by family physicians and account for more than 14 million physician visits annually.3,4

    To date, widespread agreement on the precise definition of COPD is lacking. The American Thoracic Society defines COPD as a disease process involving progressive chronic airflow obstruction because of chronic bronchitis, emphysema, or both.5 Chronic bronchitis is defined clinically as excessive cough and sputum production on most days for at least three months during at least two consecutive years.6 Emphysema is characterized by chronic dyspnea resulting from the destruction of lung tissue and the enlargement of air spaces. Asthma, which also features airflow obstruction, airway inflammation and increased airway responsiveness to various stimuli, may be distinguished from COPD by reversibility of pulmonary function deficits.5

    Mayo Clinic Q And A: Long

    DEAR MAYO CLINIC: I have chronic obstructive pulmonary disease , and my doctor is recommending an antibiotic drug long term. Why is this needed?

    ANSWER: For certain people with COPD, long-term use of an antibiotic drug specifically azithromycin is a fairly new option to reduce exacerbations. Exacerbations are episodes when symptoms of COPD become worse than their usual day-to-day variation. Some exacerbations may be caused by a viral or bacterial infection. An exacerbation, if severe, can lead to hospitalization and even respiratory failure and death.

    For people with COPD, short-term use of antimicrobials antibiotics and antiviral agents can help fight respiratory infections, such as acute bronchitis, pneumonia and influenza, and be used as part of the treatment of an exacerbation. A 2011 study indicated that long-term, continued use of azithromycin helps prevent COPD exacerbations even for those who dont have an active respiratory infection. In addition to its antibacterial effects, azithromycin has anti-inflammatory and immune-modulating effects that likely contribute to its ability to improve COPD management.

    The study included people who had COPD with an increased risk of exacerbations, most of whom already were taking other medications to prevent exacerbations. Among those who took azithromycin daily for a year, the risk of having an exacerbation declined by about 27 percent, compared to those who took an inactive substance .

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    Prevention Is Better Than Cure

    Its very important for people with long-term lung problems to have the influenza and pneumococcal vaccinations. If you have COPD or another chronic lung disease you may be eligible to receive these vaccinations for free .

    Flu vaccines are given annually. Check with your doctor about whether you need the pneumococcal vaccine.

    Pulmonary Rehabilitation After An Acute Exacerbation

    (a) Cycles of infection in COPD. The arrow depicts current ...

    Quality statement


    Quality measures


    Data source:


    Data source:

    What the quality statement means for different audiences

    Service providers Healthcare professionals Commissioners People with COPD who have had a hospital stay because of a sudden flare up of their symptoms

    Definitions of terms used in this quality statement

    Acute exacerbation
    Pulmonary rehabilitation programme
    • are at least 6 weeks in duration and include a minimum of twice-weekly supervised sessions
    • include supervised, individually tailored and prescribed, progressive exercise training including both aerobic and resistance training
    • include a defined, structured education programme.

    Equality and diversity considerations

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    Scope Of The Guideline

    The Guideline Development Group has examined the use of macrolides in adults where the duration of treatment exceeds that usually employed to treat an acute infection and the dosage is less than that usually employed to treat an acute infection. Such usage is considered to be exerting an effect through mechanisms other than a direct antibacterial one, commonly described as immunomodulatory mechanisms. We have characterised this as long-term, low-dose usage and have examined such usage in the following conditions:

    • Asthma.

    Oxygen Supplementation In Acute Copd Exacerbation

    Many patients require oxygen supplementation during a COPD exacerbation, even those who do not need it chronically. Hypercapnia may worsen in patients given oxygen. This worsening has traditionally been thought to result from an attenuation of hypoxic respiratory drive. However, increased ventilation/perfusion mismatch probably is a more important factor.

    Before oxygen administration, pulmonary vasoconstriction minimizes V/Q mismatch by decreasing perfusion of the most poorly ventilated areas of the lungs. Increased V/Q mismatch occurs because oxygen administration attenuates this hypoxic pulmonary vasoconstriction.

    The Haldane effect may also contribute to worsening hypercapnia, although this theory is controversial. The Haldane effect is a decrease in hemoglobin’s affinity for carbon dioxide, which results in increased amounts of carbon dioxide dissolved in plasma. Oxygen administration, even though it may worsen hypercapnia, is recommended many patients with COPD have chronic as well as acute hypercapnia and thus severe central nervous system depression is unlikely unless PaCO2 is > 85 mm Hg. The target level for PaO2 is about 60 mm Hg higher levels offer little advantage and increase the risk of hypercapnia.

    In patients who are prone to hypercarbia , oxygen is given via nasal prongs or Venturi mask so it can be closely regulated, and the patient is closely monitored. Patients whose condition deteriorates with oxygen therapy require ventilatory assistance.

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    Healthcare Professionals Should Consider The Risk Of Antimicrobial Resistance When Deciding Whether Antibiotics Are Needed For Treating Or Preventing A Flare Up Of Symptoms Of Chronic Obstructive Pulmonary Disease

    05 December 2018

    These new recommendations come as NICE publishes antimicrobial prescribing guidance and a separate update to its 2010 clinical guideline on diagnosing and managing COPD in over 16s.

    The antimicrobial guidance recommends that antibiotics should be offered to people who have a severe flare up of symptoms, also known as a severe acute exacerbation.

    However other factors should be taken into account when considering the use of antibiotics for treating an acute exacerbation that is not severe, such as the number and severity of symptoms.

    The guidance notes that acute exacerbations of COPD can be caused by a range of factors including viral infections and smoking. Only around half are caused by bacterial infections, so many exacerbations will not respond to antibiotics.

    Paul Chrisp, director of the centre for guidelines at NICE, said: Evidence shows that there are limited benefits of using antibiotics for managing acute exacerbations of COPD and that it is important to take other options into account before antibiotics are prescribed.

    “These recommendations will help healthcare professionals to make responsible prescribing decisions, which will not only help people manage their condition but also reduce the risk of antimicrobial resistance.

    COPD is a broad term that covers several lung conditions that make breathing difficult. Some people experience flare-ups where their symptoms are particularly severe, these are called exacerbations.

    Do Antibiotics Have A Positive Therapeutic Effect In Patients With Stable Copd

    Antibiotics in âdifficult to treatâ? asthma or the overlap syndrome – Video abstract [ID 313480]

    A total of 12 randomized control trials, involving 3,692 subjects with COPD, have been included . The results are discussed according to antibiotic. Of the 6 different antibiotics studied, 4 were macrolides: azithromycin, clarithromycin, erythromycin, and roxithromycin. One tetracycline, doxycycline, was used. One fluoroquinolone, moxifloxacin,, was used. Only 1 study looked at a combination treatment . Three of the 12 studies used pulsed antibiotic therapy.,, Sethi et al and Brill et al used pulsed moxifloxacin, whereas Mygind et al used pulsed azithromycin. The remaining 9 studies used continuous therapy. A brief description of the studies used can be found in Supplementary Table 1.

    Summary of Exacerbation-Related Outcomes Antibiotics Trials in COPD

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    Study Setting And Population

    Allegheny General Hospital is a 631-bed quaternary care teaching facility with approximately 22000 inpatient admissions yearly. The Western Pennsylvania Hospital is a 317-bed community-based teaching hospital with nearly 6800 inpatient admissions annually. Both facilities are located in Pittsburgh, Pennsylvania, and are members of the Allegheny Health Network . The evaluation was approved and granted exempt status from the AHN Institutional Review Board as it was deemed quality assessment/quality improvement.

    Antibiotics Are Medications Used For The Treatment Of Bacterial Infections But Long

    Antibiotics are medications commonly prescribed by doctors for the treatment of various illnesses. These medications can be either synthesized in the laboratory or produced naturally by other microorganisms. Antibiotics work by inhibiting the growth of bacteria. They are usually prescribed for 7 to 14 days. However, in certain cases, especially in long-term illnesses a prolonged use of antibiotics is recommended, which is normally associated with various side effects. For this reason, it is very important for your healthcare provider to weigh the cons when it comes to side effects of long-term use, as well as the pros.

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