Data Collection And Analysis
Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients, and patients admitted to the intensive care unit separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised as a single group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation, and ICU patients to have a very severe exacerbation. When authors of primary studies did not report outcomes or study details, we contacted them to request missing data. We calculated pooled risk ratios for treatment failure, Peto odds ratios for rare events , and mean differences for continuous outcomes using randomeffects models. We used GRADE to assess the quality of the evidence. The primary outcome was treatment failure as observed between seven days and one month after treatment initiation.
Antibiotics In Acute Exacerbations Of Copd: The Good The Bad And The Ugly
You may well wonder what the connection might be between the title of this editorial and the famous Western The Good, the Bad and the Ugly. Well, we know that antibiotics are effective in treating bacterial infections , are not as harmless as both clinicians and patients may think , and may have adverse effects and do not work in viral infections . There is an increasing awareness that we have to challenge the problems caused by the overuse of antibiotics. Beliefs, expectations and incentives are the drivers of antibiotic overuse among the concerned parties: patients, physicians and society. Therefore, social norms would have to be altered, resulting in a fundamental change in patients’ expectations, marketing, indications for antibiotic use and, particularly, physicians prescription behaviour. In a recent paper by the McDonnell Norms Group , some radical solutions were suggested, ranging from changes in the way physicians are paid for prescribing antibiotics and looking at accuracy and limitation of antibiotic use to patients might be reimbursed differently for antibiotic prescriptions.
Further studies should be undertaken investigating biomarkers to guide antibiotic treatment and investigate the optimal duration of antibiotic treatment.
Do Antibiotics Have A Positive Therapeutic Effect In Patients With Stable Copd
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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New Treatments For Copd
Bronchial rheoplasty
Bronchial rheoplasty is a new bronchoscopic method for the management of chronic bronchitis. The clinician inserts a specialized camera called a bronchoscope into the lungs, then delivers short bursts of electrical energy to the inner walls of the small and larger airways called the bronchi. The electrical bursts cause the excessive mucus-producing cells to break open and die, which helps regenerate healthy cells in the lungs.
Targeted lung denervation
TLD is a bronchoscopic intervention designed to disrupt pulmonary nerve reflexes, which may have the potential to reduce COPD exacerbation . The development of interventional therapies such as TLD may stabilize COPD patients and help reduce their risk of exacerbation.
Stem cell therapy
Stem cells are undifferentiated cells with the ability to become specialized cells. Theoretically, these cells can replace diseased cells and help repair and regenerate organs. There have been promising results with the use of stem cells in animal models of lung diseases. Although the U.S. FDA has approved human clinical trials for stem cell use in COPD, there is no information yet about their long-term safety or efficacy.
Lung flute
Clinical tests have proven that the lung flute can break up mucus in the lungs, making it effective for diagnostic use and therapy.
Robotic lung volume reduction surgery
Valve surgery
Azithromycin
Interleukin 5 drugs
Guidelines Urge Choosing Antibiotics Wisely
Guidelines to be published in December by the National Institute for Health and Care Excellence in the United Kingdom urge doctors to think about the risk of antibiotic resistance when considering antibiotics to prevent or treat COPD exacerbations. The draft guidelines recommend that doctors consider these factors:
- Frequency of exacerbations
- Severity of exacerbations
- Indications of pneumonia, such as the results of a chest X-ray
The draft guidelines also recommend consulting with local experts on what bacteria are circulating to choose the most effective antibiotic.
Used appropriately, antibiotics can be a valuable tool in treating patients who have COPD exacerbations, says Hill. This is particularly true in those patients who are hospitalized or who have more severe disease. Contrarily, inappropriate use of antibiotics increases costs and risks. New diagnostic tools should soon be more widely available to help clinicians make appropriate therapeutic choices.
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Antibiotics For Copd: Study Details
Dransfield assigned 570 patients with COPD to take 250 milligrams of azithromycin daily for a year. He assigned 572 others to a placebo pill that looked the same.
About 80% of the patients were also on other medications for COPD. Both groups continued taking other medications, including inhaled steroids and bronchodilators.
COPD can include chronic bronchitis or emphysema , or both.
Typically, a patient with COPD who has a flare-up is given a course of antibiotics, but not long-term, Dransfield says.
The researchers decided to look at the long-term treatment because similar regimens have shown promise in other lung diseases, including cystic fibrosis.
Patients were on average aged 65. ”To get into the study, you had to be on oxygen or reported having one of these flare-ups in the previous year,” Dransfield says.
Compared to placebo, the antibiotic reduced flare-ups by about 20%. At the one-year mark, those in the placebo group had on average 1.83 flare-ups, but those in the antibiotic group had 1.48.
During the study, there were 156 hospitalizations for COPD for the antibiotic group and 200 for the placebo group.
The antibiotic is available generically, Dransfield says. It costs about a dollar a pill.
The medicine also increased the amount of antibiotic-resistant microbes in some patients. However, no one got an infection related to that during the study.
Dransfield reports consulting and speaking fees for GlaxoSmithKline, Boehringer Ingelheim, and Forest Pharmaceuticals.
Referral And Seeking Specialist Advice
- Refer people with an acute exacerbation of COPD to hospital if they have any symptoms or signs suggesting a more serious illness or condition and in line with the NICE guideline on COPD in over 16s
- Seek specialist advice for people with an acute exacerbation of COPD if they:
- have symptoms that are not improving with repeated courses of antibiotics or
- have bacteria that are resistant to oral antibiotics or
- cannot take oral medicines .
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Breathing Machines For Sleep
This typically means a CPAP or BiPAP machine.
CPAP stands for continuous positive airway pressure. Light air pressure from the CPAP machine helps make sure your airway doesnât close and interrupt your breathing as you sleep.
The CPAP machine has a small motor that blows air into a tube that connects to a mask that covers your nose and mouth, or in some cases just your nose.
The BiPAP machine works in a very similar way. The âBiâ in BiPAP stands for âbilevel.â It means there are two levels of pressure: A normal one as you breathe in and a lower one that makes it easier to breathe out. Many people find this more comfortable than the constant airflow from a CPAP machine.
People with moderate to severe COPD may use these machines at the hospital to help with sudden, intense symptoms or at home to help with sleep and to keep blood oxygen levels up and remove carbon dioxide.
Just remember that regular use of these machines isnât always helpful for COPD. Talk to your doctor about whether you are a good candidate for consistent machine-aided breathing for your COPD.
Azithromycin May Reduce Treatment Failure In Patients With Acute Exacerbation Of Copd
A randomized controlled trial found that patients hospitalized for an acute exacerbation of chronic obstructive poulmonary disease experienced reduced rates of treatment failure when adding azithromycin to their standard of care.
Azithromycin may offer relief for patients with chronic obstructive pulmonary disease , according to a randomized controlled trial, which found that the antibiotic can reduce treatment failure in patients hospitalized with acute exacerbation of the disease.
During the study, patients received a low dose of azithromycin in addition to their prescribed medications while in the hospital and continued taking the antibiotic for 3 months following hospitalization. The result, according to the data, was reduced treatment failure compared with standard of care alone. Rates of treatment failure were under 50% for patients taking azithromycin compared with 60% for patients receiving standard of care.
Previous studies have shown that azithromycin prevents acute COPD exacerbations, but whether that antibiotic could reduce the need to intensify care of patients hospitalized for an exacerbation or improve their chances of not having another exacerbation once they left the hospital was unclear, according to a press release.
Mortality was 2% in the azithromycin arm compared with 4% in the standard of care arm.
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Prophylactic Treatment With Antibiotics
Over the years, the practice of using prophylactic antibiotics to prevent COPD exacerbation has been a matter of controversy. Research studies using azithromycin and erythromycin show that prophylactic antibiotics can reduce exacerbations.
But research also suggests that prophylactic antibiotics are associated with negative side effects that can sometimes outweigh the benefits, such as antibiotic resistance.
To date, the European Respiratory Society/American Thoracic Society guideline does not recommend the daily use of antibiotics for the treatment of COPD, except in cases of bacterial infection associated with COPD exacerbation.
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.
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Antibiotics For Acute Exacerbations In Copd: Comparison Of Effectiveness And Tolerability
A recent meta-analysis published in BMC Pulmonary Medicine found that dirithromycin had a high clinical cure rate with a low adverse effect rate in patients with acute exacerbations from chronic obstructive pulmonary disease ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole also had high clinical cure rates, but median rates of adverse effects.
The authors searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published up to September 2016 that evaluated the use of antibiotics for the treatment of acute exacerbations of COPD.
Primary study end points were clinical cure rates and adverse effects microbiological response rate, relapse of exacerbation, and mortality were analyzed as well. The researchers used a random-effect network to assess the effectiveness and tolerability of each antibiotic used in acute exacerbations of COPD.
The authors performed traditional meta-analysis for microbiological response rate, frequency of recurrence, and mortality. Only the microbiological response rate of doxycycline was significantly better than placebo . No significant results were found for frequency of recurrence or mortality rates.
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.
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Conflict Of Interest Statement
Subgroup And Sensitivity Analyses
Given that different antibiotics may have different effects on AECOPD, we conducted a subgroup analysis to explore the effects of 4 specific antibiotic classes that are most frequently used due to the recommendation by GOLD or Dutch guidelines. We also further explored the effects of antibiotics for AECOPD therapy among patients with mild COPD and those with more severe COPD. Considering the possible influence of some factors on outcome, we conducted several sensitivity analyses by limiting patients to those with only spirometry-based COPD diagnosis, those with smoking history, those aged 40 or above, and those without asthma-COPD overlap syndrome, respectively, to verify the robust of our results.
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Subgroup And Sensitivity Results
Among all the antibiotics used for AECOPD treatments in this study for COPD outpatients , doxycycline was the most frequently used antibiotic, followed by macrolides , amoxicillin , and co-amoxiclav , and only 15 cases used other antibiotics . Subgroup analysis indicated that doxycycline significantly reduced the risk of treatment failure by 4750% compared to no antibiotic treatment . Although not statistically significant, similar beneficial effects were observed for macrolides and co-amoxiclav compared to no antibiotic treatment. No statistically significant difference was observed between the amoxicillin exposed group and the reference group . There was no difference in the observed treatment effects of overall and specific antibiotics in population with mild COPD and population with more severe COPD .
Table 4.
Sensitivity analyses: odds ratio for treatment failure of index exacerbation among COPD outpatients
Criteria For Considering Studies For This Review
Types of studies
We sought to include randomised controlled trials comparing an antibiotic in the treatment group versus placebo in the control group. We included studies reported as full text, those published as abstract only, and unpublished data.
Types of participants
We planned to include patients with acute exacerbations of COPD .
We considered studies eligible if more than 90% of participants had received a clinical diagnosis of COPD or, ideally, spirometrically confirmed COPD, and if participants were over 40 years of age. For trials with physicianbased diagnosis of COPD , we considered for inclusion only those in which more than 90% of participants had a smoking history. We accepted physicianbased diagnosis of COPD because spirometry has limited value during an acute exacerbation of COPD, and because restricting the systematic review to patients with spirometrically confirmed COPD would limit inclusion to trials in which detailed medical records, including previous spirometry, were available at the time of enrolment, or in which patients at risk for exacerbation were enrolled in a stable state and were randomised when they developed an exacerbation. We excluded studies of patients with acute bronchitis, pneumonia, asthma, or bronchiectasis.
Types of interventions
Types of outcome measures
Primary outcomes
- Treatment failure as observed between seven days and one month after treatment initiation
Secondary outcomes
Assessment of heterogeneity
Data synthesis
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Other Factors Influencing Treatment Choice
- Inpatient vs. outpatient. Whether you are being prescribed the drug as an outpatient or inpatient influences treatment choice. This is because some antibiotics can only be administered in hospital settings.
- Current medical conditions and allergies. These also affect the choice of an antibiotic. Antibiotics are the most common culprit for drug-related allergies. Many of these antibiotics also have the potential for drug-drug interactions with current medications, so your doctor will attempt to select the safest agent for you.
- Local resistance patterns. Some drugs are more likely to be resistant to certain pathogens. Because of this, some drugs used in North America, for example, are not used in other countries. For example, amoxicillin is not usually used for COPD exacerbations because it does not work well against the culprit pathogens.2
- Recent use of the same antibiotic. Some doctors are hesitant to prescribe an antibiotic that you have already used within the last 3 months. This is because this practice can increase the risk of resistance to the drug class, meaning the antibiotic will not work well.3 Having said that, I have seen the same antibiotic given to the same patient within a three-month period with success. Therefore, this is not a strict rule.
