Not all flares are infectious.
Old agent for treatment and prevention of influenza A, but now precludes routine use unless circulating strains known to be sensitive.
Good activity against most S. pneumoniae, performed well in the history of AECB and cheap. Due to concern of rising resistance (5-10% of S. pneumoniae, 30-40% of H. influenzae and 90-95% of M. catarrhalis) now not frequently employed except as amoxicillin/clavulanate
It seems to work better in patients than in the test tube (susceptibility testing). Resistance rates of S. pneumoniae are high, but relevance debated.
Single-dose drug for influenza based on the half-life of up to 91 hours. It has an FDA indication for treatment of influenza in patients at high risk for complications, and also in one unpublished study works better against influenza B than oseltamivir. It also has less nausea or vomiting compared to oseltamivir. As an end-cap endonuclease inhibitor, it depresses viral shedding faster than oseltamivir. No data in hospitalized patients yet.
A bad choice, poor activity against S. pneumoniae relative to other oral cephalosporins.
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.
Risky choice due to low in vitro activities against S. pneumoniae and H. influenzae, but good historic record for AECB, well-tolerated and 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 major concern is abuse with the consequence of resistance and C. difficile infection. Tendon rupture possible even with short courses, especially if patients are frequently taking systemic corticosteroids or have ESRD.
No longer useful since most strains now resistant, so need to know current CDC recommendations.
Use for the treatment and prophylaxis of influenza virus A and B. Early treatment preferred, should be withing 48 hrs of sx onset -- if possible but use beyond this time frame is justified if severe COLD, severe infection or hospitalized patient. Expensive. Main side effect in GI intolerance and rare cases of self-injury and confusion. See the CDC website for the latest recommendations.
Limited published data but 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. Should be given within 48 hrs of the onset of sx if possible, but use later is justified if severe illness or hospitalized patient. Expensive. Main side effect is bronchospasm. The most potent of the NAIs.
(No ordered preference)
Comment: This group is supported by the NHLBI and WHO, and it’s regularly updated guidance comprises a definition of COPD and chronic bronchitis as well as a basis for recommendations in this module.
The GOLD report is revised annually since 2011. Includes definitions, comprehensive treatment recommendations. Antibiotic recommendations are what are incorporated into the ABX module. For the overall management, please launch and view the document for AECB.
Comment: Similar to bronchiectasis studies, authors look at whether certain drugs (mostly macrolides) have some effect beyond anti-infective properties. Twelve trials w/ 3784 patients reviewed. Authors thought the studies with azithromycin or erythromycin had the greatest effect with improvement on clinical bases.
Comment: Systematic review suggests that effects are small and inconsistent for both inpatients and outpatients. Effect of abx best among ICU patients. Data quality is heterogeneous and limited.
Comment: Role of azithromycin for prevention in COPD remains controversial. The authors here suggest that daily use of drugs was most helpful in older patients and with GOLD scores of 1 or 2 (milder disease). Use of the drug did seem to prevent flares that required both antibiotic and steroid therapy.
Comment: Review of trials of abx v. placebo RCTs only (2068 pts), found benefit in patients in ICU while those on non-ICU hospitalizations and outpatients were not consistent. Of note, these trials ranged in years from 1957 to 2012. There was no apparent impact on mortality or LOS in hospital for those patients.
Comment: This is a randomized controlled trial in 1,142 patients with COPD given placebo vs. azithromycin 250 mg/day. azithromycin recipients had a significant reduction in exacerbations (1.5/year vs. 1.8/year; p=< 0.001) and improved lung function.
Comment: First-line agents (ampicillin, TMP-SMX and doxycycline) vs. 2nd line (amox-CA, macrolides, quinolines and 3d gen cephalosporins). First-line agents were inferior (RR 0.5).
Comment: The authors, noted authorities on COPD, 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 that were associated with exacerbations supporting the thesis that these strains have greater pathogenic potential.
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: This systematic review examines placebo-controlled studies that are not now frequently pursued by pharma (2020) that show reduced risk of short-term mortality by 77%, treatment failure by 53% and sputum purulence by 44% if antibiotics are received. This supportive evidence applies to moderately or severely ill patients with COPD exacerbations and increased cough and sputum purulence with antibiotics.
Comment: The Buffalo group has studied this cohort of 104 pts with COPD for 10 years with monthly sputum cultures. In this study they showed M. catarrhalis was newly detected in 57 of 560 exacerbations. This was accompanied by a serologic response and clearance. They conclude M. catarrhalis causes 10% of exacerbations.
Comment: A longitudinal study of patients with COPD showing 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).
Comment: Analysis of sequential (monthly) samples of sputum 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 culture are unreliable sources 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 2 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 w/some exacerbations & there is an immune response that is strain-specific to support its potential role.
Comment: Study of 168 exacerbations - viruses found in 67 (40%) - most common were rhinovirus and RSV.
Comment: Results showed a benefit of ofloxacin with mortality decrease (4% vs 22%) & reduced duration hospitalization & mechanical ventilation. The study raised concerns about the ethics of a placebo control with such seriously ill pts, but the accompanying editorial notes that the benefit of antibiotics had never been clearly shown.
Comment: Position paper of ACP for managing exacerbations of chronic bronchitis. Indications to Rx: Increased dyspnea, increased cough AND increased sputum purulence. Agents recommended: Amoxicillin, doxycycline, TMP-SMX.
Comment: The authors show the ADVANTAGES OF MEASURING FEV-1 AND/OR PEFR for baseline evaluation and response to treatment. Both require patient effort
Comment: The authors show PHYSICIAN ESTIMATES OF THE SEVERITY OF AIRWAY OBSTRUCTION in exacerbations of COPD correlate poorly with FEV-1 measurements
Comment: 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: The data support use OF PULSE OXIMETRY to evaluate oxygenation except when O2 saturation is < 70%
Comment: There are 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.
Comment: 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 exacerbations of bronchitis 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. pneumo). S. pneumo was recovered in 37% of exacerbations & in 33% of control periods; for H. flu, it was 57% & 60%, respectively
Comment: The tracheobronchial tree below the larynx is normally sterile. This study using transtracheal aspirations 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 during exacerbations.
Comment: One of the many controlled trials of tetracycline vs. placebo in 149 patients hospitalized for AECB. There was SIGNIFICANT BENEFIT FOR TETRACYCLINE TREATMENT in terms of symptom scores and peak expiratory flow rate.
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