Treatment Of Acute Exacerbations Of Chronic Bronchitis Research Articles

Characterisation of a collection of Streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: In vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups

The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n=51) or full (n=50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55–75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3–4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8–13% for amoxicillin and cefuroxime, 35–39% for macrolides, 2–8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production.

Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis and COPD: a systematic review and meta-analysis.

To evaluate the efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (AECOPD). We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was clinical success at early follow-up. Study-level data were pooled using a random-effects model when I(2) was >50% or a fixed-effects model when I(2) was <50%. Eleven randomized controlled studies were considered. There was no difference between moxifloxacin and comparator agents with regard to treatment success in intention-to-treat (ITT) [odds ratio (OR) =1.18, 95% confidence interval (CI) 0.98-1.42], clinically evaluable (CE) (OR 1.13, 95% CI, 0.93-1.37) patients, or adverse effects in general (OR 1.00, 95% CI, 0.86-1.17). Moxifloxacin was associated with better microbiological success (OR 1.45; 95% CI, 1.14-1.85). Moxifloxacin was as clinically equivalent and bacteriologically superior to the antibiotic regimens routinely used in patients with AECB and AECOPD. Moxifloxacin therapy may be a promising and safe alternative to empirical treatment for AECB and AECOPD.

Short-course fluoroquinolones in acute exacerbations of chronic bronchitis

It is estimated that 50–70% of acute exacerbations of chronic bronchitis (AECB) are caused by bacterial infections. Appropriate selection of antimicrobials may lead to better outcomes and reduced healthcare costs. Respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) have a broad spectrum of activity against most AECB-causing pathogens and are used as first-line treatment in patients with comorbidity, severe airway obstruction or recurrent exacerbations. We review studies, identified through a MEDLINE search, that compared clinical efficacy and speed of recovery for short-course (≤5 days) fluoroquinolone therapy with commonly prescribed standard therapy (≥7 days). Among 177 studies reporting the use of fluoroquinolones for AECB treatment, 23 used a short-course regimen, shown to be at least as effective as standard therapy of 7 or more days duration. Furthermore, evidence suggests that short-course therapy offers faster resolution of symptoms, faster rate of recovery, fewer relapses, fewer and shorter hospitalizations, and longer time between recurrences.

A Phase II Study of Antofloxacin Hydrochloride, a Novel Fluoroquinolone, for the Treatment of Acute Bacterial Infections

Aims: To evaluate the clinical and bacterial efficacies and the safety of antofloxacin hydrochloride tablets in the treatment of acute exacerbations of chronic bronchitis (AECB) and acute pyelonephritis (AP). Patients and Methods: A randomized, controlled, multicenter, double-blind, double-dummy clinical trial was conducted at 6 hospitals in China. The patients in the investigational group took an oral 400-mg loading dose of antofloxacin on the first day followed by 200 mg daily. Control group patients took 200 mg of levofloxacin orally twice daily for 7–14 days. Results: A total of 284 patients were enrolled into the study, including 140 cases of AECB and 144 cases of AP; 141 patients were in the antofloxacin group and 143 patients were in the levofloxacin group. Two hundred fifty-four patients completed the entire treatment and follow-up and comprised the per-protocol analysis data set; 30 patients were excluded because of informed consent withdrawal, loss to follow-up, protocol violations, or adverse drug events. Treatment was ceased in 3 patients in the antofloxacin group and in 1 patient in the levofloxacin group because of skin rashes, dizziness, or adverse gastrointestinal effects. At the end of the 2-regimen treatment, the observed effectiveness rates for AECB were 90.3 and 87.7% for the treatment and control groups, respectively, and 96.9 and 92.1% for AP. The overall bacterial eradication rates were 95.9 and 92.4%, and drug-related adverse events were observed in 13.1 and 10.1% of patients, respectively. There were no severe adverse effects. No statistical differences in drug efficacy and safety were detected between the 2 treatment groups (p > 0.05). Conclusions: Antofloxacin hydrochloride is an effective and well-tolerated new fluoroquinolone that demonstrates clinical and bacteriological efficacies similar to levofloxacin for the treatment of AECB and AP.

Clinical efficacy of farcosolvin syrup (ambroxol&amp;ndash;theophylline&amp;ndash;guaiphenesin mixture) in the treatment of acute exacerbation of chronic bronchitis

Acute exacerbations of chronic bronchitis (AECB) are defined as recurrent attacks of worsening bronchial inflammation that are marked by an increase in the volume of daily sputum produced, a change in color of the expectorated sputum, and worsening dyspnea. Farcosolvin (Pharco Pharmaceuticals, Alexandria, Egypt) is a mixture of ambroxol (15 mg); theophylline (50 mg); and guaiphenesin (30 mg), per 5 mL syrup. To test the clinical efficacy of Farcosolvin in the treatment of AECB in a randomized, single-blinded, controlled study design. One hundred patients with AECB were randomized to either Farcosolvin or guaiphenesin treatment groups, in addition to the standard medical treatment for their cases. Baseline clinical symptomatolgy of breathlessness, cough, and sputum severity scoring were compared before and after 3 and 7 days of treatment in both groups and the differences compared between groups. Changes in perceived improvement were also compared between groups using the Clinical Global Impression of Improvement or Change Scale (CGIC). There were statistically significant improvements in breathlessness and cough scores in both groups (pretreatment versus posttreatment at day 3 and at day 7; P < 0.05). There were highly statistically significant differences between groups in improvement in breathlessness and cough scores, after 3 and 7 days treatment, in favor of the Farcosolvin treatment group (P < 0.001). Out of 50 patients, 48 (96%) in the Farcosolvin-treated group rated their improvement on the CGIC scale as "much" and "very much" improved, while only 41 patients (82%) reported such a degree of improvement in the control group. The difference was statistically significant (P < 0.05). We concluded from our study that Farcosolvin syrup might be safe and effective in improving symptoms in cases of acute exacerbation of chronic bronchitis.

Characterisation of exacerbations of chronic bronchitis and COPD in Europe: the GIANT study

The GIANT study collected information on patients with acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) and the effect of treatment with moxifloxacin. AECB history, concomitant diseases, moxifloxacin treatment, concomitant medication, clinical symptoms and adverse events were recorded. A questionnaire at the end of treatment recorded the impact on patients' daily lives. Among 9225 patients from eight European countries, marked variation was seen in characteristics including age, smoking history and type of exacerbation. Spirometry use was more common among chest physicians (66.7%) than GPs (15.5%). Patients with Anthonisen type 1 and 2 exacerbations had more frequent exacerbations and these patients experienced a greater impact on daily activities compared with patients with type 3 episodes. Patient symptoms improved with moxifloxacin treatment after a mean (SD) of 3.4 (1.8) days, allowing return to normal daily activities after 5.4 (4.4) days and with full recovery taking 6.5 (3.1) days. Characteristics of patients with AECB and acute exacerbations of COPD differ among European countries. Spirometry is under-used, particularly in primary care and antibiotic treatment does not always follow current guidelines. Results confirm the efficacy of moxifloxacin in the treatment of AECB in real-life conditions.

Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections

Background: The ketolides are a subclass of macrolides, which were designed specifically to overcome macrolide-resistant respiratory pathogens. Ketolides lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind to a secondary region on domain II of the 23S rRNA subunit. Telithromycin was the first ketolide to be approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA issued a public health advisory followed by a warning. In 2007 the indications for treatment of AECB and sinusitis were removed from the labeling. Cethromycin (ABT-773) is the only other ketolide currently under clinical development. Objective: To review currently available data on cethromycin, including chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo activity and results of treatment studies in humans. Methods: A search was made in PubMed, pharmaceutical databases and meeting abstracts using the terms ketolides, ABT-773 and cethromycin. Results/conclusions: Cethromycin has comparable tissue penetration, pharmacokinetics and in vitro activity compared with telithromycin to Streptococcus pneumoniae, including multidrug-resistant isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one published CAP treatment study that compared cethromycin 150 mg q.d. with 150 mg b.i.d. One Phase II and a Phase II/III study have been presented in abstract form, both were non-comparative, dose-ranging studies, which suggested that 150 mg q.d. or 300 mg q.d. were comparable in terms of clinical response and bacterial eradication, although data on the latter are limited. Data on side effects are limited and appear to be mainly gastrointestinal. There have been no reports of serious hepatotoxicity at the time of this writing. Cethromycin may have other uses in addition to treatment of CAP respiratory infections, including treatment of infections due to Neisseria gonorrhoeae and Chlamydia trachomatis and bioterrorism agents including Bacillus anthracis, Yersinia pestis and Francisella tularensis.

Faropenem Medoxomil

Replidyne is developing faropenem medoxomil, the ester-type prodrug of faropenem, for the treatment of bacterial infections and respiratory tract infections, including acute exacerbations of chronic bronchitis (AECB), acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP). Faropenem medoxomil is also being developed for the treatment of tonsillitis, pharyngitis and otitis media in children. Faronpenem medoxomil was discovered by scientists at Suntory Institute for Biomedical Research (now Asubio Pharma). The compound has significantly improved oral bioavailability and is dehydropeptidase-I stable. Following absorption, faropenem medoxomil is rapidly hydrolysed to the active drug faropenem. An NDA was filed in the US but was deemed not approvable by the US authorities. Following the termination of the license agreement between Replidyne and Forest Laboratories, Replidyne is now exploring other partnering opportunities for faropenem medoxomil. Daiichi Suntory Pharma (now Asubio Pharma) has granted Replidyne the exclusive rights to faropenem medoxomil for the US and Canada and an exclusive option to develop and commercialize the compound in the rest of the world, excluding Japan. Replidyne has rights to the preclinical and clinical data generated up to the time of the agreement (August 2004) and will complete clinical development of the drug. Replidyne is also developing a paediatric formulation for the treatment of common bacterial infections. In February 2006, Replidyne sublicensed development, commercialization and distribution rights of faropenem medoxomil in the US to Forest Laboratories Holdings (Forest Laboratories). However, the agreement was terminated in February 2007, following the US FDA's non-approvable letter for the product. Replidyne re-acquired all US adult and paediatric rights previously granted to Forest. Bayer AG previously licensed exclusive worldwide rights to develop faropenem medoxomil from Suntory (now Asubio Pharma) and conducted a number of phase III clinical trials. This agreement appears to have been superseded by the agreement with Replidyne in 2004. In April 2007, Daiichi Asubio Pharma was renamed as Asubio Pharma Co., Ltd. Daiichi Asubio Pharma was the name used by Daiichi Suntory Pharma after it became a wholly owned subsidiary of Daiichi Pharmaceutical in September 2005. Daiichi Suntory Pharma was the joint venture company owned by Daiichi Pharmaceutical and Suntory. In April 2006, Daiichi Pharmaceutical merged with Sankyo to form Daiichi Sankyo Inc. The FDA issued a non-approvable letter in October 2006 for faropenem medoxomil in the treatment of ABS, CAP, AECB and uncomplicated skin and skin structure infections. Consequently, drug development has reverted back to phase III in the US. The agency has indicated that four phase III trials in three adult respiratory indications, ABS, CAP and AECB, will be required for a US marketing application. According to this advice, Replidyne may be required to conduct one superiority study (versus placebo) each for the ABS and AECB indications and two non-inferiority, active-controlled studies for the treatment of CAP. The required dose of faropenem medoxomil in future trials will be 600 mg, administered twice daily, and trials will involve approximately 1500 patients to ensure an acceptable database of safety information for review. Replidyne is continuing to work with the FDA on further trial details. Replidyne first filed the NDA seeking approval for faropenem medoxomil in December 2005. This submission marked the first marketing approval application for faropenem medoxomil worldwide. The NDA, which was accepted in February 2006, was primarily based on data from 11 phase III trials in patients with respiratory tract and skin infections; the safety data included information from more than 5000 patients treated with the drug. The proposed commercial name for faropenem medoxomil, Orapemtrade mark, was not approved by the FDA due to its similarity to another commercially approved drug. Replidyne and the FDA are working together to identify a suitable alternative. Two phase III trials have been conducted that demonstrated faropenem medoxomil was non-inferio o azithromycin and clarithromycin in the treatment of AECB. Replidyne's phase II trial evaluating an oral liquid formulation of faropenem medoxomil (7.5-40 mg/kg) in paediatric patients with acute otitis media (AOM), met its primary endpoint. The trial was completed in March 2007 and enrolled approximately 310 patients in Costa Rica and Israel. Replidyne intends to meet with the US authorities to discuss the design of the planned phase III trial in paediatric AOM. In addition to 5 years of Hatch-Waxman exclusivity granted upon approval, faropenem medoxomil is protected by an issued US composition of matter patent, which expires in 2015. Extension of exclusivity under Hatch-Waxman legislation is expected.

EFFICACY OF ANTIMICROBIALS FOR ACUTE EXACERBATION OF CHRONIC BRONCHITIS EPISODES

PURPOSE: Efficacy of antimicrobials for acute exacerbations of chronic bronchitis (AECB) episodes to prevent hospitalization and slow decline in pulmonary function in patients with chronic obstructive pulmonary disease (COPD) is controversial. Previously, a study performed at our medical center identified risk factors for antimicrobial failure and further hospitalization for AECB treatment. A similar study in COPD patients to better understand antimicrobial utilization in AECB and its impact on outcome is being described here.

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.

Pharmacokinetic and Pharmacodynamic Aspects of Oral Moxifloxacin 400 mg/day in Elderly Patients with Acute Exacerbation of Chronic Bronchitis

To assess the pharmacokinetic and pharmacodynamic behaviour of moxifloxacin in 15 consecutive elderly patients with acute exacerbation of chronic bronchitis (AECB) treated with the fixed oral moxifloxacin 400 mg/day regimen with the intent of verifying which degree of exposure may be ensured by this standard regimen against AECB pathogens. This was an open-label, observational, pharmacokinetic-pharmacodynamic study. Blood samples were collected at steady state at appropriate intervals. Moxifloxacin plasma concentrations were analysed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters and pharmacodynamic determinants (peak concentration [C(max)]/minimum inhibitory concentration [MIC], area under the plasma concentration-time curve during the 24-hour observational period [AUC(24)]/MIC, pharmacodynamic breakpoints [PDBPs]) were assessed. The mean estimated pharmacokinetic parameters (C(max) 4.40 mg/L at 1.4 hours, AUC(24) 42.67 mg . h/L, elimination half-life 12.55 hours, total body clearance 0.16 L/h/kg) were generally similar to those observed in both young and elderly historic controls (except for higher-dose normalised C(max) and lower volume of distribution of the central compartment). Median C(max)/MIC and AUC(24)/MIC ratios for moxifloxacin in the fully assessable cases were, respectively, 67.5 and 823.9 against Streptococcus pneumoniae, 25 and 310.2 against Moraxella catharralis and 416.5 and 3647.5 against Haemophilus influenzae. Mean estimates of PDBP for achieving C(max)/MIC values of 12.2 and AUC(24)/MIC values of 125 were 0.36 and 0.35 mg/L, respectively. In patients with AECB the pharmacokinetic behaviour of moxifloxacin is not significantly altered by aging processes. This is consistent with moxifloxacin being metabolised mainly by means of phase II hepatic reactions, the activity of which was shown not to decline with age. Both the pharmacokinetic and pharmacodynamic analyses suggest that moxifloxacin 400 mg/day may be a valid therapeutic approach in the treatment of AECB in the elderly. Of note, the unmodified pharmacokinetic behaviour with no need for age-related dosage adjustments combined with the once-daily administration favouring compliance and the low potential for drug-drug pharmacokinetic interactions in case of polytherapy, make moxifloxacin particularly attractive in the treatment of elderly subpopulations at a very high risk of AECB.

A review of guidelines for antibacterial use in acute exacerbations of chronic bronchitis

Acute exacerbations of chronic bronchitis (AECB) affect a significant proportion of the adult population worldwide and are associated with a substantial socioeconomic burden. The majority of episodes of AECB are bacterial in aetiology and patients are generally treated empirically with orally administered antibacterial agents. Guidelines for the management of AECB have been developed by a number of national health authorities and international organisations, with the aim of promoting rational selection of antibacterial therapy to minimise the risk of treatment failure and subsequent hospitalisation while containing the development and spread of antibacterial resistance. This paper reviews a number of recently published or updated AECB treatment guidelines, focusing on patient stratification strategies, antibacterial treatment recommendations, and newer antibacterial treatment options, including respiratory fluoroquinolones and the ketolide telithromycin, which have recently been added to a number of national treatment guidelines.

Five-Day Telithromycin Once Daily Is as Effective as 10-Day Clarithromycin Twice Daily for the Treatment of Acute Exacerbations of Chronic Bronchitis and Is Associated With Reduced Health-Care Resource Utilization

To demonstrate equivalence in the clinical efficacy of telithromycin vs clarithromycin treatment of outpatients with acute exacerbations of chronic bronchitis (AECB), and to compare the tolerability and respiratory-related health-care resource utilization associated with these treatment regimens. A randomized, double-blind, multicenter, clinical study was conducted at 105 centers in 14 countries. Adult outpatients (age > or = 30 years) received oral telithromycin, 800 mg qd for 5 days (n = 270), or oral clarithromycin, 500 mg bid for 10 days (n = 282), for the treatment of AECB. Clinical and bacteriologic outcomes were assessed at the posttherapy/test-of-cure (TOC) visit (days 17 to 24; per-protocol population). Health-care resource utilization data were collected for each patient by investigators blinded to study medication up to the late posttherapy visit (days 31 to 36). Clinical cure rates at the posttherapy/TOC visit were comparable between the groups (telithromycin, 193 of 225 patients [85.8%]; clarithromycin, 206 of 231 patients [89.2%]); bacteriologic outcome was satisfactory for 59 of 72 telithromycin-treated patients (81.9%) vs 63 of 76 clarithromycin-treated patients (82.9%). Health-care resource utilization assessed up to the late posttherapy visit was lower in the telithromycin treatment group than the clarithromycin treatment group, with significantly fewer hospitalizations for respiratory-related causes (one hospitalization vs eight hospitalizations for a total of 4 inpatient days vs 39 inpatient days, respectively), significantly fewer AECB-related emergency department visits (0 vs 8), and fewer unscheduled outpatient visits (11 vs 18). Fewer telithromycin-treated patients reported days lost from work (21 of 91 patients [23.1%]; 133 days) compared with those receiving clarithromycin (30 of 98 patients [30.6%]; 141 days). Telithromycin was well tolerated; adverse events considered possibly related to study medication were reported by 61 of 269 patients (22.7%) and 100 of 280 patients (35.7%) receiving telithromycin and clarithromycin, respectively. In this study, 5-day telithromycin treatment was as effective and well tolerated as 10-day clarithromycin treatment for patients with AECB, and was associated with a reduced utilization of health-care resources.

Antibiotic activity of telithromycin and comparators against bacterial pathogens isolated from 3,043 patients with acute exacerbation of chronic bronchitis

BackgroundAntimicrobial therapy is considered an important component in the medical management of most patients with acute exacerbation of chronic bronchitis (AECB). The three predominant bacterial species isolated are nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Staphylococcus aureus is also frequently isolated while atypical bacteria are thought to cause up to 10% of exacerbations. Antibacterial resistance is increasing worldwide and little surveillance data exist concerning pathogens isolated from patients with AECB.MethodsThis study examines the prevalence of antibacterial resistance in isolates obtained from patients with clinically diagnosed AECB. A total of 3043 isolates were obtained from 85 centres in 29 countries, between 1999–2003, and were tested against the new ketolide telithromycin and a panel of commonly used antibiotics.Results and DiscussionOf the S. pneumoniae isolates, 99.9% were susceptible to telithromycin, but only 71% were susceptible to erythromycin and 75.3% to penicillin. Of the H. influenzae isolates, 99.6% were susceptible to telithromycin. 11.7% of these isolates produced β-lactamase. Almost 10% of S. pneumoniae were multidrug-resistant; 99.0% of these isolates were susceptible to telithromycin. Telithromycin also demonstrated good in vitro activity against M. catarrhalis (MIC90 = 0.12 mg/L) and was the most active compound against methicillin-susceptible S. aureus (98.9% susceptible).ConclusionTelithromycin demonstrated similar or better activity against the bacterial species investigated than the other agents, with the most complete coverage overall. These species are the predominant causative bacterial pathogens in AECB and thus the spectrum of activity of telithromycin makes it a potential alternative for the empirical treatment of AECB.

Acute exacerbation of chronic bronchitis: expanding short-course therapy

Recent management guidelines for acute exacerbation of chronic bronchitis (AECB) have provided antimicrobial options for different classes of patients according to varying disease severity or risk of treatment failure. In a pivotal, double-blind, double-dummy study comparing azithromycin microspheres (2 g single dose) with the respiratory quinolone levofloxacin (500 mg once daily × 7 days) for the treatment of AECB, the two regimens were equally effective and well tolerated in patients with mild-to-moderate disease (clinical cure rate 93.6% vs. 92.7%, respectively [95% confidence interval (CI) for difference, −3.4,5.5] and overall bacteriological eradication rate 91.9% vs. 94.4%, respectively (95% CI for difference, −8.8, 3.8). Interestingly, additional post hoc analyses suggest that a single dose of azithromycin also provides comparable clinical efficacy to levofloxacin in patients with a forced expiratory volume in 1 s (FEV 1) of less than 70% of the predicted value, a risk factor that would place them in a more severe stratum. These data support azithromycin microspheres as an appropriate option in patients with mild-to-moderate AECB. The potential role of this preparation and other macrolides in patients at higher risk of therapeutic failure requires additional prospective data.

Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8 h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28–35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis

This randomized, double-blind study evaluated the efficacy and safety of a short, 5-day course of telithromycin, a new ketolide antibacterial, compared with a standard 10-day course of amoxicillin/clavulanate, in the treatment of acute exacerbations of chronic bronchitis (AECB). The study enrolled 325 adult patients with AECB and a history of chronic obstructive pulmonary disease (COPD). Patients received either telithromycin 800mg once daily (qd) for 5 days (followed by placebo for 5 days) or amoxicillin/clavulanate 500/125mg three times daily (tid) for 10 days. Clinical cure rates for telithromycin post-therapy (Days 17–21, test-of-cure) and late post-therapy (Days 31–36) were 86.1 and 78.1%, respectively; 82.1 and 75.0% for amoxicillin/clavulanate. Excellent clinical cure rates were also observed for high-risk patients. Bacteriologic outcome was satisfactory for 69.2% of telithromycin recipients vs 70.0% for amoxicillin/clavulanate recipients. Both treatments were generally well tolerated, although the frequency of drug-related adverse events was almost two-fold higher for amoxicillin/clavulanate (25.0 vs. 13.1%). Thus, a 5-day course of telithromycin 800mgqd is an effective and well-tolerated alternative to a standard 10-day course of amoxicillin/clavulanate 500/125mg tid for first-line empiric treatment of AECB in adults with COPD.

Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis

Background: Recognizing acute exacerbations of chronic bronchitis (AECB) and selecting appropriate antibiotic treatment for patients who would benefit most is a challenge for community-based physicians.Objective: The Tequin Clinical Experience Study, an open-label, noncomparative, post-marketing trial, assessed the efficacy and tolerability of gatifloxacin, an 8-methoxy fluoroquinolone, in the treatment of AECB in the community-practice setting.Methods: Consecutive patients with respiratory tract infections in community-based settings were eligible for participation. Treated patients (N = 2512) included 1107 men (44.1%) and 1405 women (55.9%) aged ≥18 years with a clinical diagnosis of chronic bronchitis. All participants received oral gatifloxacin 400 mg once daily for 7 to 10 days. Clinical response was determined via telephone contact conducted by the investigator or study coordinator using case-report forms or during an office visit after the last dose. The investigator or coordinator collected expectorated or induced sputum specimens that were then smeared on a microscope slide, stored in a tube, and transported to a central reference laboratory for Gram-staining and culture. Of 1388 pretreatment sputum specimens submitted, pathogens were isolated from 424.Results: The most frequently detected pathogens were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. All H influenzae and 99% of S pneumoniae isolates tested were susceptible to gatifloxacin. Of the 2267 patients with a determinable clinical response, 2084 (91.9% [95% CI, 90.8%–93.0%]) were cured (all acute symptoms improved or returned to baseline level, no new symptoms present, no additional antibiotic required). The 95.8% cure rate in 166 patients with H influenzae included 100% of those with beta-lactamase-positive strains. Overall, 89.2% of 111 patients with M catarrhalis were cured; rates were similar regardless of beta-lactamase production. The clinical cure rate in 74 patients with S pneumoniae was 98.6% and was independent of the degree of penicillin resistance (minimum inhibitory concentration ≥2.0 μg/mL). All 6 patients infected with S pneumoniae fully resistant to penicillin were cured. Gatifloxacin was generally well tolerated, and the majority of adverse events were mild to moderate; only 11 drug-related adverse events in 10 patients (0.4%) were serious. Drug-related nausea (3.0%), dizziness (1.5%), diarrhea (1.2%), and vomiting (0.9%) were the most common adverse events.Conclusions: The high clinical cure rate and favorable tolerability support gatifloxacin as a rational choice for the treatment of AECB in patients such as those in this community-based study.

Efficacy and Safety of Short Course (5-day) Moxifloxacin vs 7-day Ceftriaxone in the Treatment of Acute Exacerbations of Chronic Bronchitis (AECB)

The aim of this multicenter, open, randomized study was to compare the efficacy and tolerability of a 5-day treatment course with oral moxifloxacin (MXF) vs a 7-day course with i.m. ceftriaxone (CRO) in 476 patients with acute exacerbations of chronic bronchitis (AECB), and to conduct a cost minimization analysis of the two treatments from the perspectives of both the Italian National Health Service (INHS) and society. The study was conducted in Italy. Clinical success rates at test-of-cure in the 423 patients of the PP (Per Protocol) population (primary efficacy parameter) were 90.6% and 89.0% for MXF and CRO, respectively. Statistical non-inferiority of MXF vs CRO was confirmed. Similar results were found between study drugs on the secondary efficacy parameters, including success at end-of-treatment (95.3% for MXF vs 92.9% for CRO), success at test-of-cure in bacteriologically-positive patients (94.1% vs 90.7%) and eradication/presumed eradication rates (91.7% vs 93.3%). ITT (Intention-to-Treat) analysis confirmed these data. There was a low incidence of adverse events (10.8% vs 9.1%). During a 6-month follow-up period, relapse rates were lower for MXF vs CRO (23.3% vs 28.3%; p>.05). Compared with CRO, MXF was associated with cost savings per patient ranging from €226.57 (INHS perspective) to €448.23 (societal perspective), with lower hospitalization rate the major variable contributing to reduced costs. MXF appears to be an ideal candidate for AECB treatment.

Antibacterials and Acute Exacerbation of Chronic Bronchitis

The utility of antibacterials in the management of acute exacerbations of chronic bronchitis (AECB) and the related lung pathology, chronic obstructive pulmonary disease (COPD), has been debated for decades. Data presented in this article document that more expensive antimicrobials may be favored in AECB treatment to prevent adverse outcomes to patients, namely antimicrobial failure and hospitalization. Identified patient-specific variables that may lead to treatment failure include right- or left-sided heart failure and ≥4 exacerbations/year. Risk factors for hospitalization include age ≥65 years and severe pulmonary and nonpulmonary dysfunction. However, these risk factors have never been formally validated in a prospective, randomized trial. Drug-resistant organisms have not been documented to cause antimicrobial failure or hospitalization, however, more data are needed in this growing area.