Purulent Exacerbations Of Chronic Bronchitis Research Articles

Guideline for the management of chronic obstructive pulmonary disease – 2011 update

To revise the South African Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD) based on emerging research that has informed updated recommendations. (1) Smoking is the major cause of COPD, but exposure to biomass fuels and tuberculosis are important additional factors. (2) Spirometry is essential for the diagnosis and staging of COPD. (3) COPD is either undiagnosed or diagnosed too late, so limiting the benefit of therapeutic interventions; performing spirometry in at-risk individuals will help to establish an early diagnosis. (4) Oral corticosteroids are no longer recommended for maintenance treatment of COPD. (5) A therapeutic trial of oral corticosteroids to distinguish corticosteroid responders from non-responders is no longer recommended. (6) Primary and secondary prevention are the most cost-effective strategies in COPD. Smoking cessation as well as avoidance of other forms of pollution can prevent disease in susceptible individuals and ameliorate progression. Bronchodilators are the mainstay of pharmacotherapy, relieving dyspnoea and improving quality of life. (7) Inhaled corticosteroids are recommended in patients with frequent exacerbations and have a synergistic effect with bronchodilators in improving lung function, quality of life and exacerbation frequency. (8) Acute exacerbations of COPD significantly affect morbidity, health care units and mortality. (9) Antibiotics are only indicated for purulent exacerbations of chronic bronchitis. (10) COPD patients should be encouraged to engage in an active lifestyle and participate in rehabilitation programmes. Treatment recommendations are based on the following: annual updates of the Global Obstructive Lung Disease (GOLD), initiative, that provide an evidence-based comprehensive review of management; independent evaluation of the level of evidence in support of some of the new treatment trends; and consideration of factors that influence COPD management in South Africa, including lung co-morbidity and drug availability and cost. Holistic management utilising pharmacological and nonpharmacological options are put in perspective. Working groups of clinicians and clinical researchers following detailed literature review, particularly of studies performed in South Africa, and the GOLD guidelines. BENEFITS, HARMS AND COSTS. The guideline pays particular attention to cost-effectiveness in South Africa, and promotes the initial use of less costly options. It promotes smoking cessation and selection of treatment based on objective evidence of benefit. It also rejects a nihilistic or punitive approach, even in those who are unable to break the smoking addiction. These include primary and secondary prevention; early diagnosis, staging of severity, use of bronchodilators and other forms of treatment, rehabilitation, and treatment of complications. Advice is provided on the management of acute exacerbations and the approach to air travel, prescribing long-term oxygen and lung surgery including lung volume reduction surgery. The COPD Working Group comprised experienced pulmonologists representing all university departments in South Africa and some from private practice, and general practitioners. Most contributed to the development of the previous version of the South African guideline. GUIDELINE SPONSOR: The meeting of the Working Group of the South African Thoracic Society was sponsored by an unrestricted educational grant from Boehringer Ingelheim and Glaxo-Smith-Kline.

Epidemiology and Treatment of Chronic Bronchitis and Its Exacerbations

Epidemiology and Treatment of Chronic Bronchitis and Its Exacerbations

Comparative clinical and microbiological study of amoxycillin-clavulanic acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis

In a retrospective study, the clinical and microbiological efficacy of amoxycillin-clavulanic acid and ciprofloxacin were evaluated in outpatients observed within the previous year who were affected by acute purulent exacerbations of chronic bronchitis. Of the 95 patients included in the trial, 50 received amoxycillin 875 mg-clavulanic acid 125 mg 8-hourly for 10 days and 45 received ciprofloxacin 500 mg 12-hourly before meals for 10 days. Of the amoxycillin-clavulanic acid-treated patients, 90% showed clear clinical improvement and in 10% treatment failed. In the ciprofloxacin group, 75.5% of patients showed improvement and in 24.5% treatment failed. All pathogens isolated prior to therapy were susceptible to the antibiotic used for therapy. At the end of treatment, in the amoxycillin-clavulanic acid-treated group, 84% of strains were eradicated and 8% persisted; others were superinfections. In the ciprofloxacin group, 57.7% of strains were eradicated, 26.6% persisted and 15.5% were superinfections. No clinically significant side effects were observed in either group. Overall, amoxycillin-clavulanic acid demonstrated superior clinical and microbiological efficacy to ciprofloxacin, although this might be attributable to the higher proportion of aerobic Gram-negative pathogens in the ciprofloxacin group.

Clinical and bacteriological experience with cefodizime in acute purulent exacerbations of chronic bronchitis.

1 or 2 g doses of cefodizime i.m. were studied in 287 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis, mostly associated with Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis. Pharmacokinetic studies in serum and sputum on the first treatment day yielded mean peak serum concentrations of 50 to 100 mg/l, with corresponding sputum concentrations of 1.4 and 2.7 mg/l, after the two respective doses. No great differences were found between the clinical and microbiological results in the various dosage groups, and no corresponding improvement was noted with the highest dosages studied. In general, infection was eliminated in 90 to 95% of patients at the end of treatment, and in approximately 70 to 80% after a follow-up week. Some infections associated with beta-lactamase producing M. catarrhalis persisted or relapsed after treatment. Unwanted drug effects were recorded in five patients, leading to discontinuation in two. It is concluded that a single daily intramuscular dose of 1 g cefodizime for seven days produces satisfactory results in most patients.

Meningococcal chest infections in a general hospital

In the course of one calendar year (1989-1990), 46 specimens of respiratory secretions (from 44 patients) cultured in the microbiology department of a large district general hospital in The Netherlands were found to yield Neisseria meningitidis. Twenty-eight of the 46 samples yielded pure cultures of meningococci and 18 yielded other recognised respiratory pathogens as well. Only one patient had pneumonia, whereas 19 had acute respiratory infections and 18 acute purulent exacerbations of chronic bronchitis. The remaining patients, who had a variety of symptoms, all had purulent sputum. Only 8 of the 44 patients were under 40 years of age; 21 were aged more than 60 years. Serological grouping and subtyping showed a predominance of group B strains (in 24 of 44 patients) and 13 strains were non-groupable. The importance of recognising or overlooking meningococci in cultures of respiratory secretions is discussed.

Temafloxacin: is effective in acute purulent exacerbations of chronic bronchitis

Temafloxacin: is effective in acute purulent exacerbations of chronic bronchitis

Temafloxacin in acute purulent exacerbations of chronic bronchitis

Temafloxacin hydrochloride, a new fluoroquinolone, was given orally in doses of 300 or 600 mg twice daily for ten days to 36 patients, all hospitalized because of severe acute purulent exacerbations of chronic bronchitis. Sputum cultures before, during and after treatment showed that the infection was eliminated in 12/18 evaluable patients given 300 mg and in 13/16 receiving the 600 mg doses. Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae were effectively eliminated, but only half the Pseudomonas aeruginosa infections were eradicated. MICs for most pathogens were 1 mg/l or less (including the majority of the pneumococci) but the MICs for Ps. aeruginosa ranged from 0.5 to greater than 16 mg/l, those for 10 of the 22 strains being greater than 2 mg/l. Pharmacokinetic studies on serum and sputum specimens showed serum Cmax values of 3.5 and 6.0 mg/l, the sputum Cmax being 2.35 and 4.17 mg/l after the different doses. No interaction with concomitant theophylline could be found. Two patients complained of moderate nausea or water-brash. Temafloxacin can be considered safe and effective at these dosages, but for Ps. aeruginosa infections higher dosages need to be investigated.

Cefodizime and cefotaxime in acute exacerbations of chronic bronchitis: a randomized double-blind prospective study in 180 patients

In a double-blind prospective study, 180 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis were treated for seven days with twice daily 1 g intramuscular injections of either cefodizime or cefotaxime. Sputum cultures performed before, during and immediately after treatment showed complete eradication of the infection in 89/90 given cefodizime and 86/90 receiving cefotaxime. Some symptomatic Pseudomonas aeruginosa superinfections occurred with each agent. During the follow-up week, recurrences or reinfections after apparent clearance occurred in 15 patients given cefodizime and in 21 receiving cefotaxime. Pharmacokinetic studies in blood showed mean Cmax values of 50.8 mg/l for cefodizime and 36.5 mg/l for cefotaxime, corresponding values in the sputum being 1.61 and 0.62 mg/l. Mean AUC values in both blood and sputum were 2 1/2- to 3-fold higher for cefodizime. Some features suggested better performance by cefodizime than by cefotaxime, but the clinical results were not statistically significantly different.

Azithromyrin (CP-62,993) in acute exacerbations of chronic bronchitis: an open clinical, microbiological and pharmacokinetic study

A group of 21 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis was treated for five days with a new oral macrolide azithromycin. They received one dose of 500 mg on the first day, followed by 250 mg once daily thereafter. Pre-treatment sputum cultures were typical for this district, but the cultures during and after treatment showed many Haemophilus influenzae infections persisting. Geometric mean MICs of azithromycin for these organisms rose from 1.23 mg/l (pre-treatment) to 4.87 mg/l, a week after the end of treatment. The mean MICs for erythromycin also rose four-fold. Streptococcus pneumoniae and Branhamella catarrhalis strains were effectively eradicated. Pharmacokinetic studies on serum and sputum from the first treatment day showed relatively low serum Cmax values, averaging 0.63 mg/l, but with considerable individual variation. However, peak sputum concentrations averaged 3.7 mg/l. Nevertheless, the clinical and microbiological results were not encouraging because of the failure to eradicate H. influenzae with the drug dosage used in this study.

Treatment of acute exacerbations of chronic bronchitis with ciprofloxacin.

Thirty four patients with acute purulent exacerbations of chronic bronchitis were treated with 500 mg ciprofloxacin twice daily, orally, for ten days. Short time cure rate was 97% (cure 71%, improvement 26%) and failure 3%, long time cure rate (six months follow-up) was 74%. Predominant initial pathogens were Haemophilus influenzae and Streptococcus pneumoniae, mostly in pure cultures. All sputum cultures except those with Streptococcus pneumoniae became negative on the third day of treatment. Apart from a slower clearance of pneumococci from sputum there were no significant differences in responses between pneumococcal and Haemophilus infections during and after therapy. Mild adverse gastrointestinal effects were noticed in five patients.

Amoxycillin/clavulanate in acute purulent exacerbations of chronic bronchitis.

Twenty patients, all admitted to hospital with acute purulent exacerbations of chronic bronchitis associated with Haemophilus influenzae, Streptococcus pneumoniae or beta-lactamase producing Branhamella catarrhalis were treated twice daily for ten days with amoxycillin/clavulanate. Ten patients were first given 1000 mg amoxycillin with 200 mg potassium clavulanate intravenously bd for three days, before crossing to the standard oral regimen of 1000 mg amoxycillin + 250 mg potassium clavulanate bd. Clinical results on day 10 were excellent in 16/20 patients, but 14 patients developed recurrences or reinfections within a week of the end-of-treatment, five of them with beta-lactamase producing B. catarrhalis. Bacteriological and kinetic studies showed that the branhamella beta-lactamases were inhibited by 0.25 mg/l clavulanic acid and that the mean sputum concentration of clavulanic acid was 0.16 mg/l, that of amoxycillin being 0.92 mg/l. The importance of the follow-up of such infections is stressed.

Ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis.

Eighty hospital patients with acute purulent exacerbations of chronic bronchitis associated with Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis or Pseudomonas aeruginosa were treated with ciprofloxacin. The patients were divided into four groups of 20 patients each and administered either 500 mg, 750 mg (two different batches of tablets) or 1000 mg twice daily for ten days. Most of the patients with Haemophilus influenzae and Branhamella catarrhalis infections were treated successfully but the results in patients with Streptococcus pneumoniae and Pseudomonas aeruginosa infections were less satisfactory. Although the ciprofloxacin MICs for the latter organisms were relatively low, mean serum and sputum concentrations measured on the first day of treatment did not exceed 2-3 mg/l and 1-2.3 mg/l respectively. The overall clinical results for all dosage regimes were only fair, mainly due to failure to eradicate Streptococcus pneumoniae and Pseudomonas aeruginosa. Adverse effects (nausea, stomach pain or hallucinations) were seen in eight patients, causing treatment to be discontinued in five. It is concluded that ciprofloxacin is only of limited use in the treatment of respiratory tract infections unless Streptococcus pneumoniae is absent.

The quinolones in chronic bronchitis.

Results are presented from 186 hospitalized patients treated for acute purulent exacerbations of chronic bronchitis with orally administered ciprofloxacin (80 patients), enoxacin (26 patients), ofloxacin (30 patients) or pefloxacin (50 patients). In general, good clinical results were observed in 50-70% of the patients treated, most failures being due to relapses or reinfections with Streptococcus pneumoniae or Pseudomonas aeruginosa. Studies on blood and sputum concentration suggested that gastro-intestinal absorption was not always satisfactory. Unwanted drug effects were noted with all agents studied, generally presenting as stomach pain, nausea, hallucinations, or dizziness. Most adverse drug reactions were seen with enoxacin, often but not always during concomitant treatment with theophylline.

Ciprofloxacin in acute exacerbations of chronic bronchitis.

Thirty four patients with acute purulent exacerbations of chronic bronchitis were treated with 500 mg ciprofloxacin twice daily, orally, for ten days. The short-term response rate was 97% (cure 70.6%, improvement 26.4%) and failure 3%; the long-term response rate (six months follow-up) was 73.5%. Predominant initial pathogens were Haemophilus influenzae and Streptococcus pneumoniae, mostly in pure cultures. All sputum cultures except those with Str. pneumoniae became negative on the third day of treatment. Apart from a slower clearance of pneumococci from the sputum there were no significant differences in responses between pneumococcal and Haemophilus infections during and after therapy. Peak serum levels at 2 h after administration were 3.8 +/- 1.7 mg/l, half life was 3 h; peak sputum levels at 4 h were 1.3 +/- 0.95 mg/l. The serum-sputum penetration was 49.7% measured by AUC values. Mild adverse gastrointestinal effects were noticed in five patients.

Doxycycline in respiratory infections: a re-assessment after 17 years.

Seventeen years after a previous study of doxycycline in acute purulent exacerbations of chronic bronchitis, a similar investigation was repeated. Forty patients with bacteriologically proven infections were given 100 mg doxycycline twice daily (by mouth) for ten days. The clinical results in Branhamella catarrhalis infections were excellent as were those with Streptococcus pneumoniae, but one patient developed septicaemia with a resistant pneumococcus while under therapy. Treatment was unsuccessful in a third of the patients with Haemophilus influenzae infections. Overall, excellent or good results were recorded in 74% of patients at the end of treatment, and in 64% a week later. Doxycycline is still a useful oral antibiotic in this condition and possibly the best for B. catarrhalis infections, especially with beta-lactamase producing strains.

Pefloxacin in acute exacerbations of chronic bronchitis.

Forty-three patients admitted to hospital with acute purulent exacerbations of chronic bronchitis were treated with 400 mg pefloxacin twice daily for ten days. The first 20 patients were given the first dose of the drug as a 60 min intravenous infusion. Serum and sputum concentrations of pefloxacin were measured microbiologically at intervals on the first treatment day and the sputum was cultured before, during, and after the course of pefloxacin. Two patients died from unrelated causes during the follow-up and one refused to continue treatment. All strains of Haemophilus influenzae and Branhamella catarrhalis were eradicated at end-of-treatment but eight strains of Streptococcus pneumoniae and three of Pseudomonas aeruginosa were cultured and the sputum remained purulent despite the pefloxacin. Peak serum concentrations averaged approximately 4.5 mg/l after the infusion and 5 mg/l on oral administration, the corresponding sputum concentrations being 3.8 and 4.6 mg/l, respectively. MICs for H. influenzae were 0.06 mg/l, or less. Mode MICs for the pre- and post-treatment strains of Str. pneumoniae were 4 and 16 mg/l, and the corresponding values for Ps. aeruginosa were 2 and 16 mg/l. The poor results in pseudomonas and pneumococcal infections could largely be explained by the degree of resistance among these organisms.

Serum and sputum concentrations of enoxacin after single oral dosing in a clinical and bacteriological study.

Fifteen patients admitted to hospital with acute purulent exacerbations of chronic bronchitis were treated with enoxacin by mouth (three 200 mg capsules twice daily) for ten days. Sputum was cultured before, during and after the treatment course. Serum and sputum concentrations were measured microbiologically at intervals on the first treatment day. Blood was assayed before, and 1, 1 1/2, 2, 2 1/2, 3, 5 and 7 h after the first dose and purulent unhomogenized sputum was tested in samples collected 0-2, 2-4, 4-6 and 6-8 h after this dose. The highest concentrations in serum were usually noted 2 or 2 1/2 h after the medication and ranged from approximately 3 to 6 mg/l (average 4.08 mg/l). The highest sputum concentrations were generally found in the 2-4 or 4-6 h portions, and ranged from 2.2 to 6 mg/l (average 3.68 mg/l). The areas under the serum and sputum concentration-time curves were both calculated to be 17.03 mg/l.h (0-7 h values) whereas the projected 0-12 h values were 25.2 and 26.9 mg/l.h, respectively. The drug concentrations declined slowly in serum and sputum with half-lives of approximately 5 and 4 h. Penetration from blood to sputum as judged on peak to peak ratios was approximately 90%, whereas the AUC value ratios showed penetration ranging from 100 to 107.5%. Unfortunately, 9 of the 15 patients had to abandon the treatment (mostly on the third day) due to unwanted drug effects (principally nausea, but some patients had hallucinations, dizziness or epileptiform attacks) possibly related to interference with theophylline metabolism.

Ceftriaxone in acute purulent exacerbations of chronic bronchitis.

A group of 36 patients, admitted to hospital because of acute purulent exacerbations of chronic bronchitis, were treated with once daily injections of ceftriaxone for 10 days, 17 receiving 1 g injections and 19 patients 2 g doses. At the end of treatment (day 11) six patients remained infected (three with Branhamella catarrhalis and three with Pseudomonas aeruginosa) but during the 7 follow-up days 12 patients developed infections with beta-lactamase producing strains of Bran. catarrhalis, Ps. aeruginosa was cultured from 2 patients and Streptococcus pneumoniae from 3 more. Kinetic studies confirmed the long half-life of ceftriaxone (13 to 14 h in this patient group) and showed average peak serum concentrations of 31 mg/l after 1 g and 43 mg/l after the 2 g dose. The comparable sputum concentrations were 3.5 and 4.8 mg/l, respectively. However, four patients failed to show any ceftriaxone in the sputum despite simultaneous blood concentrations of between 32 and 50 mg/l and in two patients ceftriaxone only appeared in the sputum 12 h after the injection. All except one harboured beta-lactamase-producing Bran. catarrhalis in the sputum, and the possibility of breakdown of ceftriaxone by branhamella beta-lactamases is suggested.

A simple oral antimicrobial regimen effective in severe chronic bronchial suppuration associated with culturable Haemophilus influenzae.

Three grams of amoxycillin administered twice daily for seven days, as an oral powder (Amoxil 3G sachets, Bencard) dispersed in water, to 17 patients with bronchiectasis resulted in striking clinical, spirometric and bacteriological improvement in 11 of 12 patients who were producing purulent sputum from which Haemophilus influenzae was cultured by a selective bacteriological technique (Roberts & Cole, 1980). In the five patients from whose sputum this organism could not be cultured, and in one from whom it could, there was no improvement. Untoward effects were limited to nausea in one patient and acceptability of the regimen by the remaining patients was unanimous. There was no evidence of accumulation of the drug in serum or sputum. The rapidity of effect and oral form of the treatment suggest that it may provide a simple out-patient regimen for chronic bronchial sepsis and severe purulent exacerbations of chronic bronchitis from which H. influenzae can be cultured.

The tetracyclines in purulent exacerbations of chronic bronchitis.

The tetracyclines in purulent exacerbations of chronic bronchitis.