Not all flares are infectious.
Drug | Recommendation |
An old agent for treating and preventing influenza A, it now precludes routine use unless circulating strains are known to be sensitive. | |
Good activity against most S. pneumoniae performed well in the history of AECB and cheap. Due to concern about rising resistance (5-10% of S. pneumoniae, 30-40% of H. influenzae and 90-95% of M. catarrhalis), it is now not frequently employed except as amoxicillin/clavulanate. | |
Expands amoxicillin activity to cover all H. influenzae and M. catarrhalis, usually highly active vs. S. pneumoniae. | |
It works better in patients than in the test tube (susceptibility testing). S. pneumoniae resistance rates are high, but their relevance is debated. AECB exacerbations can be treated with azithromycin, not only preferentially in smokers. However, there is an increased incidence of bacterial resistance emergence and hearing test impairments. There is also solid evidence that long-term azithromycin reduces exacerbations over one year. | |
Single-dose drug for influenza based on the half-life of up to 91 hours. It has an FDA indication for the treatment of influenza in patients at high risk for complications and also appears to work better against influenza B than oseltamivir. It also causes less nausea or vomiting than oseltamivir. As an end-cap endonuclease inhibitor, it depresses viral shedding faster than oseltamivir. | |
A bad choice, poor activity against S. pneumoniae relative to other oral cephalosporins. | |
Active against most strains of S. pneumoniae and all strains of H. influenzae and M. catarrhalis. About as active as amoxicillin vs. S. pneumoniae. Relatively expensive, well-tolerated. | |
Active against most strains of S. pneumoniae and all strains of H. influenzae and M. catarrhalis. Somewhat less active than amoxicillin vs. S. pneumoniae. Relatively expensive, well-tolerated. | |
Active against most strains of S. pneumoniae and all strains of H. influenzae and M. catarrhalis. Somewhat less active than amoxicillin vs. S. pneumoniae. Relatively expensive; well-tolerated. | |
Active against most strains of S. pneumoniae and all strains of H. influenzae and M. catarrhalis. Somewhat less active than amoxicillin vs. S. pneumoniae. Relatively expensive; well-tolerated. | |
As active as azithromycin and erythromycin vs. S. pneumoniae; activity vs. H. influenzae is debated due to activity ascribed to a metabolic product, which is greater than that of the parent compound. FDA has approved for H. influenzae pneumonia but would not rely on it for severe infection. | |
The drug has lower in vitro activities against S. pneumoniae and H. influenzae, but it has a good historical record for AECB, is well-tolerated and is cheap. This is usually a good choice for patients who aren’t very sick. | |
Active against nearly all treatable pathogens except influenza virus, including S. pneumoniae, H. influenzae, M. catarrhalis, most S. aureus (MSSA), most GNB, Chlamydophila pneumoniae and Mycoplasma pneumoniae. The drug is easy to take (once daily) and well-tolerated. The primary concern is abuse with the consequence of resistance and C. difficile infection. Tendon rupture is possible even with short courses, especially if patients are frequently taking systemic corticosteroids or have ESRD. | |
It is no longer helpful since most strains are now resistant, so need to know current CDC recommendations. | |
Use for the treatment and prophylaxis of influenza viruses A and B. Early treatment is preferred, and it should be within 48 hours of sx onset if possible. However, use beyond this time frame is justified if the patient has a severe COLD or severe infection or is hospitalized. It is expensive. The main side effects are GI intolerance and rare cases of self-injury and confusion. See the CDC website for the latest recommendations. | |
Limited published data, reasonable activity vs. the major pathogen, and generally well tolerated except for hypersensitivity reactions to a sulfa moiety. | |
Neuraminidase inhibitor (NAI) for the treatment of influenza A or B. Given by inhalation, the aerosolized form is contraindicated for persons with reactive airways and, therefore, not used in patients with COPD. |
Comment: The GOLD report has been revised annually since 2011. You may go to https://goldcopd.org/ for updates to this report. Includes definitions and comprehensive treatment recommendations. Antibiotic recommendations are incorporated into the ABX module. For the overall management beyond abx, please launch and view the document for AECB.
Comment: Procalcitonin appears to have the best performance (compared to CRP and others) in finding bacterial pathogens present in sputum. However, this analysis did not explore the outcomes further.
Comment: Since GOLD emphasizes sputum purulence for consideration of antibiotics, this group looked at six studies, all observational. Hence, the data quality is not high, and ID clinicians have long known that viral infections can cause purulence. Based on these data, it seems that there is moderate evidence to suggest that in those with AECB/COPD exacerbations, yellow or green sputum has a higher probability of likely pathogenic bacteria.
Comment: Like bronchiectasis studies, authors examine whether certain drugs (primarily macrolides) have some effect beyond anti-infective properties. Twelve trials w/ 3784 patients reviewed. The authors thought the studies with azithromycin or erythromycin had the most significant impact with improvement on clinical bases.
Comment: A systematic review suggests that effects are small and inconsistent for both inpatients and outpatients. The effect of abx is best among ICU patients. Data quality is heterogeneous and limited.
Comment: The role of azithromycin in the prevention of COPD remains controversial. The authors suggest that daily drug use was helpful in older patients with GOLD scores of 1 or 2 (milder disease). The drug did seem to prevent flares that required both antibiotic and steroid therapy.
Comment: This randomized controlled trial in 1,142 patients with COPD given a placebo vs. azithromycin 250 mg/day. azithromycin recipients significantly reduced exacerbations (1.5/year vs. 1.8/year; p=< 0.001) and improved lung function.
Comment: The authors noted authorities on COPD and examined genetic differences between 59 H. influenza strains implicated in exacerbations of COPD and 73 that merely colonized the lower airway in these patients. They noted gene patterns associated with exacerbations, supporting the thesis that these strains have greater pathogenic potential.
Rating: Important
Comment: This systematic review examines placebo-controlled studies not now frequently pursued by pharma (2020). These studies show that antibiotics reduce the risk of short-term mortality by 77%, treatment failure by 53% and sputum purulence by 44% if received. This supportive evidence applies to moderately or severely ill patients with COPD exacerbations and increased cough and sputum purulence with antibiotics.
Comment: Patients with AECB were randomized to treatment with moxifloxacin or placebo. Clinical cure was significantly associated with antibiotic treatment (OR 1.5) and negatively associated with age >65 and bronchodilator use. The conclusion was that the benefit of moxifloxacin was seen primarily in those >65 yrs.
Comment: The Buffalo group has studied this cohort of 104 patients with COPD for 10 years with monthly sputum cultures. In this study, they showed that M. catarrhalis was newly detected in 57 of 560 exacerbations. This was accompanied by a serologic response and clearance. They conclude that M. catarrhalis causes 10% of exacerbations.
Comment: A longitudinal study of patients with COPD shows some exacerbations are associated with an immune response to a newly acquired strain of H. influenzae. (This supports the role of H. flu as a pathogen in exacerbations). It appears that acquiring a new strain plays a role even if it is colonized.
Comment: Analysis of sequential (monthly) sputum samples from patients with COPD defined a group with a less than six-month lapse with negative cultures for H flu. The subsequently recovered strain was identical to the initial isolate, suggesting it was always there and that sputa cultures were an unreliable source of this agent.
Comment: Viruses implicated in 168 cases in 83 patients are: All viruses - 66 (40%), Rhinovirus - 59% (of the 66), RSV - 29%, Coronavirus -11%, influenza - 16%.
Comment: The author reviews methods and conclusions of studies to determine exacerbations of COPD with two categories: 1) Conventional: sputum culture, serology & placebo-controlled trial; 2) New: Bronchoscopic sampling, molecular epi of sputum isolates, immune response & markers of airway inflammation. Most exciting are the new methods, which include studies showing a new strain of H. influenzae is associated with w/some exacerbations & there is an immune response that is strain-specific to support its potential role.
Comment: Results showed a benefit of ofloxacin, with a mortality decrease (4% vs 22%), reduced duration of hospitalization, and mechanical ventilation. The study raised concerns about the ethics of a placebo control with such seriously ill patients, but the accompanying editorial notes that the benefit of antibiotics had never been clearly shown.
Rating: Important
Comment: The authors show PHYSICIAN ESTIMATES OF THE SEVERITY OF AIRWAY OBSTRUCTION in exacerbations of COPD correlate poorly with FEV-1 measurements.
Comment: This was one of many controlled trials of amoxicillin vs. placebo, this one with 262 outpatients with AECB. Analysis by symptom score and peak expiratory flow rate showed NO ADVANTAGE FOR ANTIBIOTICS.
Comment: There have been many trials of antibiotics, but this is the BEST AND MOST QUOTED TRIAL. Anthonisen et al. studied 362 exacerbations and showed that antibiotics have a significant benefit, but only when the exacerbation is relatively severe with at least 2 of the major 3 symptoms--increased cough, sputum, and sputum purulence. Clinical success was noted in this group for 75% of antibiotic recipients vs. 63% of placebo recipients. This is close, but the number of patients was sufficiently high to push it over the p=0.05 threshold for statistical significance.
Rating: Important
Comment: It is one of the MOST COMPREHENSIVE STUDIES EVER DONE by culture techniques. The authors followed a group of pts with chronic bronchitis & obtained quantitative bacterial cultures of sputum & viral cx at 2-week intervals. They showed that bronchitis exacerbations were often due to viral infection (positive cultures in 32% of exacerbations vs. < 1% in periods of stability), sputum bacterial culture showed no significant changes in either frequency of recovery or counts of the big 2--H. flu & S. pneumoniae). S. pneumoniae was recovered in 37% of exacerbations & 33% of control periods; for H. flu, it was 57% & 60%, respectively. The study was done when a more significant portion of the population were smokers.
Comment: The tracheobronchial tree below the larynx is usually sterile. This transtracheal aspirations study shows that about one-third of patients with chronic bronchitis have COLONIZATION OF THE LOWER AIRWAYS by the same bacteria implicated as the major causes of AECB--H influenzae and S. pneumoniae. This presumably accounts for the common observation that sputum cultures show the same bacteria during stability and exacerbations.
Comment: One of the many controlled trials of tetracycline vs. placebo in 149 patients hospitalized for AECB. There was a SIGNIFICANT BENEFIT FOR TETRACYCLINE TREATMENT regarding symptom scores and peak expiratory flow rate.