Bacterial Exacerbations Of Chronic Bronchitis Research Articles

Activity of moxifloxacin on biofilms produced in vitro by bacterial pathogens involved in acute exacerbations of chronic bronchitis

The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45–70% in E. coli and 35–70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5 h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5–4 mg/L) resulted in a breakdown of initial biofilm of 60–80% in H. influenzae and S. pneumoniae, 48–86% in S. aureus, 37–69% in M. catarrhalis and 51–71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition.

Telithromycin: the perils of hasty adoption and persistence of off-label prescribing.

Telithromycin (Ketek) was approved in April 2004 for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), bacterial sinusitis, and community-acquired pneumonia. The approval of telithromycin was controversial due to trial irregularities, noninferiority study designs, and use of foreign safety data. Safety concerns involving hepatotoxicity, myasthenia gravis exacerbation, and visual disturbances were increasingly documented in the literature after approval. On February 12, 2007, the U.S. Food and Drug Administration (FDA) removed the bacterial sinusitis and ABECB indications and strengthened safety warnings for telithromycin. To (1) assess the prevalence and distribution of on-label telithromycin utilization before and after the revisions of the product label and (2) assess the association of pivotal events in the life cycle of telithromycin with its use as reflected in pharmacy and medical claims. Using retrospective administrative medical and pharmacy claims from a large midwestern commercial insurer with an eligible membership of 1.8 million members, individuals with a telithromycin claim during January 1, 2007, through April 13, 2007, were identified. Their medical claims within 30 days prior to or on the initial telithromycin claim were analyzed for the presence of an on-label diagnosis code. Monthly telithromycin and clarithromycin claim totals per million members from January 2004 through March 2007 were calculated. Claim totals were plotted to identify utilization trends in relation to the FDA health advisory for telithromycin on January 20, 2006, and the telithromycin label changes on February 12, 2007. The medical diagnosis analysis consisted of 507 members with 1 or more medical claims with dates of service within 30 days of at least 1 pharmacy claim for telithromycin. Using the original approved telithromycin indications, 52.3% (256 of 507) of telithromycin use was on-label. The most common on-label diagnoses were sinusitis (33.9%) and bronchitis (14.4%). A diagnosis of pneumonia was present for 3.9% of telithromycin utilizers. After the February 12, 2007, label change limiting telithromycin to community-acquired pneumonia, on-label use was 6.7% (12 of 179) of utilizers. Telithromycin claims were first detected in August 2004 and overtook the clarithromycin rate of 729 claims per million members in January 2005, reaching a peak rate of 940 claims per million members in January 2006. Telithromycin monthly claims remained higher than clarithromycin until April 2006, 3 months after the liver toxicity health advisory. In comparison with January 2006, the January 2007 telithromycin claims were 186 claims per million members, a decrease of 80%. Despite revised FDA indications and safety warnings, fewer than 1 in 15 active telithromycin users have a medical claim consistent with the only currently approved indication (pneumonia). Pharmacy claims for telithromycin dropped substantially following reports of severe hepatotoxicity and strengthened safety warnings. The high prevalence of telithromycin off-label use despite hepatotoxicity and other safety risks is cause for continued concern.

Macrolides, quinolones and amoxicillin/clavulanate for chronic bronchitis: a meta-analysis

The comparative effectiveness and safety of macrolides, quinolones and amoxicillin/clavulanate (A/C) for the treatment of patients with acute bacterial exacerbation of chronic bronchitis (ABECB) was evaluated in the present study. PubMed, Current Contents and the Cochrane Central Register of Controlled Trials were searched to identify relevant randomised controlled trials (RCTs). In total, 19 RCTs (20 comparisons) were included in the present analysis. There was no difference regarding treatment success in intention-to-treat and clinically evaluable patients between macrolides and quinolones, A/C and quinolones or A/C and macrolides. The treatment success in microbiologically evaluable patients was lower for macrolides compared with quinolones (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.31-0.69). Fewer quinolone-recipients experienced a recurrence of ABECB after resolution of the initial episode compared with macrolide-recipients during the 26-week period following therapy. Adverse effects in general were similar between macrolides and quinolones. Administration of A/C was associated with more adverse effects (mainly diarrhoea) than quinolones (OR 1.36, 95% CI 1.01-1.85). Macrolides, quinolones and amoxicillin/clavulanate may be considered equivalent for the treatment of patients with an acute bacterial exacerbation of chronic bronchitis in terms of short-term effectiveness. Quinolones are associated with better microbiological success and fewer recurrences of acute bacterial exacerbation of chronic bronchitis than macrolides, while amoxicillin/clavulanate is associated with more adverse effects than both comparators.

P842 An open-label, randomised, comparative study of the patient compliance, efficacy and safety of treatment with clarithromycin extended-release versus clarithromycin immediate-release for the treatment of acute bacterial exacerbation of chronic bronchitis

P842 An open-label, randomised, comparative study of the patient compliance, efficacy and safety of treatment with clarithromycin extended-release versus clarithromycin immediate-release for the treatment of acute bacterial exacerbation of chronic bronchitis

R2315 Comparison of macrolides, quinolones, and amoxicillin/clavulanic acid for the treatment of patients with acute bacterial exacerbations of chronic bronchitis: a meta-analysis of randomised controlled trials

R2315 Comparison of macrolides, quinolones, and amoxicillin/clavulanic acid for the treatment of patients with acute bacterial exacerbations of chronic bronchitis: a meta-analysis of randomised controlled trials

Abbott Canada has launched the fluoroquinolone gemifloxacin [Factive] for the 5-day treatment of acute bacterial exacerbations of chronic bronchitis

Abbott Canada has launched the fluoroquinolone gemifloxacin [Factive] for the 5-day treatment of acute bacterial exacerbations of chronic bronchitis

P1184 Comparison offirst with second-line antibiotics for acute bacterial exacerbations of chronic bronchitis: a meta-analysis of randomised controlled trials

P1184 Comparison offirst with second-line antibiotics for acute bacterial exacerbations of chronic bronchitis: a meta-analysis of randomised controlled trials

Comparison of patient compliance with once-daily and twice-daily antibiotic regimens in respiratory tract infections: results of a randomized trial

Patient compliance seems to be highly dependent on the number of daily doses. However, it is unclear whether this effect is still present in the case of infrequent regimens during short-term antibiotic treatment. The aim of this study was to find out whether a once-daily antibiotic regimen provides better patient compliance in the case of common respiratory tract infections than a twice-daily regimen. Outpatients with acute bacterial exacerbation of chronic bronchitis were treated with clarithromycin 250 mg twice daily or clarithromycin in modified release formulation 500 mg once daily, for 7 days in a prospective, randomized, single-centre study. Patient compliance was assessed with electronic monitoring. Of 122 patients randomized, 119 were evaluable (58 in the once-daily group and 61 in the twice-daily group). All the studied parameters indicated significantly better compliance with the once-daily versus twice-daily antibiotic formulation: overall compliance (93.7% versus 81.3%, P < 0.0001), days with correct number of doses taken (80.3% versus 68.6%, P < 0.0001), correct interdose intervals (74.4% versus 56.4%, P < 0.001), and the mean interdose intervals (95.6% versus 106.3% of the expected values, P < 0.001). The study has proved much better patient compliance with a once-daily versus a twice-daily antibiotic regimen. This effect has been marked in both dosing and timing compliance. These findings indicate the clinical usefulness of a once-daily antibiotic regimen in assuring patient compliance during the treatment of respiratory tract infections.

Cefdinir: an oral cephalosporin for the treatment of respiratory tract infections and skin and skin structure infections

Cefdinir is an oral third-generation cephalosporin (also known as an advanced-spectrum or generation cephem) with good in vitro activity against the pathogens responsible for community-acquired respiratory tract infections and uncomplicated skin and skin structure infections. The drug distributes very well in respiratory tract tissues and fluids, as well as skin blisters and ear fluids; its pharmacokinetic profile allows once- or twice-daily administration. Oral cefdinir 300 mg twice daily or 600 mg once daily in adults and adolescents, or 14 mg/kg/day in one or two daily doses in pediatric patients, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy, at least equivalent to that of other oral agents in randomized controlled trials conducted in patients with community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, sinusitis, acute otitis media, pharyngitis and uncomplicated skin and skin structure infections. Cefdinir is well tolerated and the oral suspension has shown superior taste or palatability over other comparator oral antimicrobial agents. Thus, cefdinir continues to represent an important cephalosporin option for the treatment of adult, adolescent and pediatric patients with mild or moderate respiratory tract or cutaneous infections, especially in areas with elevated rates of β-lactamase production in Haemophilus influenzae and where resistance to other commonly used agents has emerged (e.g., macrolides, penicillins, tetracyclines, fluoroquinolones and trimethoprim–sulfamethoxazole).

Role for 5‑day, once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis

ABSTRACTBackground: Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course.Patients and methods: The study population was derived from two multicenter, randomized, double-blind (North America)/single-blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000 mg once daily for 5 days or a comparator agent – clarithromycin immediate-release (IR) 500 mg twice daily for 7 days (in North America) or telithromycin 800 mg once daily for 5 days (in France).Results: A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen.Conclusion: A once daily, 5‑day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB.

Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis

Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500 mg once a day (qd) for 3 days) was compared with moxifloxacin (400 mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1 s (FEV 1) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10–12 (90% versus 90%, respectively) and Days 22–26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10–12 was 93% versus 84%, respectively, and at Days 22–26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.

Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections

ABSTRACTObjective: To compare safety data with levofloxacin 500 mg and 750 mg from clinical trials for the treatment of respiratory infections.Methods: We compared adverse event data for levofloxacin 500 mg and 750 mg from clinical trials in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and community-acquired pneumonia. Adverse events occurring after the initiation of therapy were classified as treatment-emergent adverse events (TEAE); drug-related adverse events (DRAE) were TEAE assessed by the clinical investigator as definitely/very likely or probably related to levofloxacin therapy.Results: Overall, the safety profile of the two doses was similar but not identical. TEAE occurred in 49.0% (1601/3268) of those treated with 500 mg and in 45.5% (519/1141) of those treated with 750 mg ( p = 0.042); the corresponding rates of DRAE were 7.6% (248/3268) and 8.0% (91/1141) ( p = 0.699). There was no statistically significant difference in terms of overall TEAE and DRAE rates within each of the three infectious conditions, but there were in specific events, all of which are expected with levofloxacin therapy. The limitations of this analysis include that it utilized a subset of available safety data, that it includes data only from clinical trials, and that we report primarily on events occurring in ≥ 2% of patients.Conclusions: Given similar adverse event profiles and the advantages of higher dose therapy, including shorter courses of therapy and potential impact on preventing resistance, clinicians should consider utilizing the 750 mg dose of levofloxacin when choosing between dosage strengths for treatment of indicated infections.

Chronic obstructive pulmonary disease: clinical signs and infections

Chronic obstructive pulmonary disease (COPD) is a pathological condition that involves excessive production of mucus, chronic cough and inflammatory changes leading to airway limitation. The most common cause of COPD is cigarette smoking. COPD can be categorized into either chronic bronchitis or emphysema; both conditions can be differentiated by age and the production of copious, tenacious sputum. Patients with COPD are susceptible to pulmonary infections of bacterial or viral origin. Nurses should be aware of the subtle differences in conditions and the usefulness of antibiotics in the treatment of acute bacterial exacerbations of chronic bronchitis.

Levofloxacin 750 mg QD for five days versus amoxicillin/clavulanate 875 mg/125 mg BID for ten days for treatment of acute bacterial exacerbation of chronic bronchitis: A post hoc analysis of data from severely ill patients

This post hoc analysis of data from a previous randomized, blinded, multicenter, parallel, noninferiority study assessed the bacterial etiology, symptom resolution, and tolerability of severe acute bacterial exacerbation of chronic bronchitis (ABECB) patients treated with either levofloxacin 750 mg QD for 5 days or amoxicillin/clavulanate 875 mg/125 mg BID for 10 days. Severe ABECB was defined as ABECB and forced expiratory volume in 1 second (FEV1) <50% of the predicted value, or (FEV1) of 50% to 65% of the predicted value plus comorbidities, or ≥4 exacerbations per year. A total of 369 patients were included in the intent-totreat (ITT) population (187 treated with levofloxacin and 182 treated with amoxicillin/clavulanate), and 175 patients were microbiologically assessable (MA) (86 treated with levofloxacin and 89 treated with amoxicillin/clavulanate). In the ITT population, the mean age was 58.7 years, 49.1 % were male, and 48.2% were current smokers. At the on-treatment visit, a significantly higher proportion of MA patients in the levofloxacin group resolved purulent sputum production (57.5% vs 35.6%; P < 0.006), sputum production (65.4% vs 45.3%; P < 0.013), and cough (60.0% vs 44.0%; P < 0.045), compared with the amoxicillin/clavulanate group. However, no significant between-group differences were observed at posttreatment. A total of 341 pathogens were isolated, of which 143 (41.9%) were traditional ABECB flora, 181 (53.1%) were other gram-negative organisms, and 17 (5.0%) were gram-positive organisms. Overall susceptibility of the pathogens was 97.1% for levofloxacin and 90.6% for amoxicillin/clavulanate (P < 0.001). The prevalence of treatment-emergent adverse events was 42.1 % in patients who received levofloxacin and 48.6 % in those who received amoxicillin/clavulanate (95% CI,-4.0 to 17.0).

Macrolide immunomodulatory effects and symptom resolution in acute exacerbation of chronic bronchitis and acute maxillary sinusitis: a focus on clarithromycin

Bacterial respiratory tract infections are common in the primary care setting and patients often seek the assistance of a healthcare professional in order to achieve resolution of their symptoms. Antibiotic agents that offer rapid symptom relief, in addition to excellent bacteriological and clinical cure, are highly desired. Macrolides have proven to be highly effective in treating acute bacterial exacerbations of chronic bronchitis and acute maxillary sinusitis. In addition, immunomodulatory effects that may contribute to symptom resolution have been reported. This article reviews current literature on symptom resolution in acute bacterial exacerbations of chronic bronchitis and acute maxillary sinusitis, with a focus on clarithromycin, and explores the potential mechanisms that may contribute to this action.

Clarithromycin extended-release in community-acquired respiratory tract infections

Clarithromycin extended-release (ER) is a second-generation macrolide with bactericidal activity against a broad group of pathogens. It allows for convenient once-daily dosing (2 x 500 mg/day), and has less severe adverse effects than the immediate-release (IR) formulation of the drug, which may result in improved patient compliance. Clarithromycin ER has been approved for the treatment of community-acquired pneumonia, acute maxillary sinusitis and acute bacterial exacerbation of chronic bronchitis. In comparison to the IR formulation, clarithromycin ER demonstrates prolonged absorption from the gastrointestinal tract, allowing for once-daily dosing with improved gastrointestinal tolerability. Various double-blind, randomised clinical trials and group studies have found clarithromycin ER to be an efficacious treatment option, comparable with clarithromycin IR, or its other competitors.

THE EFFECT OF DISEASE SEVERITY ON CLINICAL OUTCOME WITH ACUTE EXACERBATION OF CHRONIC BRONCHITIS PATIENTS TREATED WITH GEMIFLOXACIN

PURPOSE: Gemifloxacin is approved to treat acute bacterial exacerbations of chronic bronchitis (AECB). Patients with AECB associated with COPD and a history of recurrent acute episodes can be difficult to treat. Data from 10 AECB clinical trials were analysed for number of exacerbations in last year (NELY), disease duration, history of asthma or chronic bronchitis.

Appropriate outpatient treatment of acute bacterial exacerbations of chronic bronchitis

Acute exacerbations of chronic bronchitis (AECB), which are characteristic of chronic obstructive pulmonary disease (COPD), contribute to morbidity and decreased quality of life for patients with COPD. A significant proportion of these exacerbations are due to bacterial infections. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria provide guidance for choosing the optimal drug at its optimal dose and duration for antimicrobial treatment of AECB due to bacterial infection. Evidence-based guidelines recommend stratifying patients according to risk factors to improve selection of targeted antimicrobial therapy. With increasing rates of resistance to some antimicrobials, resistance is also an important consideration for reducing treatment failures and decreasing the need for further pharmacologic treatment. Fluoroquinolones are recommended as first-line therapy for patients with chronic bronchitis who have risk factors; gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly encountered pathogens. Safety profiles are an important consideration because adverse events and poor tolerability can reduce patient adherence rates, which in turn can lead to poorer outcomes. Safety profiles also become an important consideration as shorter-course, higher-dose therapies become more prevalent. First-line therapy with a well-tolerated antibiotic that is active against the predominant pathogens, combined with low resistance rates and a convenient once-a-day dosing regimen, may reduce overall costs. Fluoroquinolones exhibit low resistance, good activity levels, and high respiratory penetration, and they are particularly well suited for shorter-course, higher-dose regimens in selected patients. Shorter-course, higher dose regimens, in turn, may be more effective, cost-efficient, and appropriate for controlling the rise of resistance than standard regimens.

Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg

This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

Clinical Significance of the Infection-FreeInterval in the Management of Acute Bacterial Exacerbations of Chronic Bronchitis

Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.