Treatment Of Acute Bacterial Exacerbations Research Articles

Electrochemical Study of the Interaction Between the Antibacterial Drug Gemifloxacin and dsDNA Using Pencil Graphite Electrode

Gemifloxacin (GMF) is a broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. The investigation of the GMF - double-stranded DNA (dsDNA) interaction using an electrochemical DNA-biosensor, showed for the first time clear evidence of interaction with dsDNA. The interaction between GMF and dsDNA onto pencil graphite electrode (PGE) was assessed at pH 4.80 acetate buffer using differential pulse voltammetry (DPV). The interaction mechanism was disclosed with the decrease of the guanine oxidation peak current. The changes in the experimental parameters such as the accumulation time and the concentration of GMF were studied. Linearity of the guanine oxidation signals was obtained in response to the range of 0.5 – 8.0 μg/mL GMF. Detection and quantification limits in the range of μg/mL were determined. Keywords: Biosensor, dsDNA, Voltammetry, Guanine, Gemifloxacin.

Prophylactic antibiotic therapy in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) represents a huge epidemiological burden and is associated with a high incidence of morbidity and mortality. The disease is characterized by chronic inflammation and bacterial colonization. Chronic bacterial colonization leads to chronic inflammation and epithelial damage that in turn may increase bacterial colonization and predispose to acute bacterial infection. Acute exacerbations are a major cause of hospitalization and lead to a deterioration in pulmonary function. Antibiotic treatment of acute bacterial exacerbations is a cornerstone of medical treatment. Conversely, the role of antibiotic prophylaxis in COPD in the stable state is controversial. From a theoretical point of view, antibiotic prophylaxis is intriguing as it could break the vicious circle between chronic bacterial colonization, inflammation and epithelial damage; however, evidence is scarce. This paper reviews the literature and focuses on the most recent data shedding light on this fascinating dilemma.

Gemifloxacin use in the treatment of acute bacterial exacerbation of chronic bronchitis.

The newest generation of fluoroquinolones have proven efficacy against bacterial organisms associated with acute exacerbation of chronic bronchitis (AECB). Gemifloxacin, as one of the quinolones in this class, exhibits many of the pharmacokinetic and pharmacodynamic characteristics of the class with a few notable differences. Against Streptococccus pneumoniae it has a lower minimal inhibitory concentration (MIC) than the other respiratory fluoroquinolones and it has activity against both bacterial DNA gyrase and topoisomerase IV. The increased activity of gemifloxacin against both enzymes may be associated with decreased rates of resistance. Clinically, gemifloxacin has been shown to have positive effects on length of hospitalization and increased success at long-term follow-up in AECB patients. These associations were observed in noninferiority comparison studies. Although an advantage with the use of gemifloxacin in AECB is suggested, there are no comparison data is available to conclude that gemifloxacin is superior to the other respiratory fluoroquinolones. Gemifloxacin is generally well tolerated, but is associated with a characteristic rash and gastrointestinal upset as its most common observed side effects.

Treatment of acute bacterial exacerbations of chronic bronchitis

Background: Controversies persist regarding the optimal management of patients with acute exacerbations of chronic bronchitis (AECB). Objective: To evaluate the available evidence on relevant issues, namely the need for administering antimicrobials in patients with AECB, the identification of the subgroup of patients with AECB needing antibiotics, the antimicrobial regimen of choice and its optimal duration, the existence of new agents, and the value of non-antimicrobial regimens for AECB. Methods: Data from various sources of evidence, including recent relevant meta-analyses, were appraised. Conclusion: Administration of antimicrobial agents, combined with bronchodilators and systemic corticosteroids, is warranted in approximately half of AECBs (i.e., in bacterial exacerbations) to achieve a survival benefit. Simple clinical parameters, mainly sputum purulence, and biomarkers, such as procalcitonin, are useful in identifying patients requiring antibiotics. Advanced antibiotics (quinolones, macrolides, or amoxicillin/clavulanic acid) are more effective than ‘old’ antibiotics in AECB; regimens of short duration (for 5 days) are preferred. There is no difference between several classes of advanced antibiotics regarding their short-term effectiveness; however, quinolones are associated with better long-term outcomes than macrolides. Newer quinolones and new formulations of macrolides enrich clinicians' armamentarium against AECB.

Moxifloxacin: update and perspectives after 8 years of usage

Moxifloxacin has a broad spectrum of activity, including Gram-positive and Gram-negative organisms, atypical respiratory pathogens, anaerobes and penicillin- and macrolide-resistant Streptococcus pneumoniae. It achieves good tissue penetration and high concentrations in clinically relevant tissues and fluids. It is available in both an oral and intravenous formulation, has a once-daily administration and a good tolerance and safety profile. Moxifloxacin is used mainly for the treatment of acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, acute bacterial sinusitis, complicated skin and skin-structure infections and complicated intra-abdominal infections, as well as pulmonary TB, although it is not approved in this indication. The most recent studies covering these clinical indications are discussed.

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.

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

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

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.

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).

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.

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.

Comparative efficacy of once daily, 5-day short-course therapy with clarithromycin extended-release versus twice daily, 7-day therapy with clarithromycin immediate-release in acute bacterial exacerbation of chronic bronchitis

ABSTRACTObjective: The objective of this study was to compare the efficacy, tolerability, and safety of two clarithromycin regimens, extended-release (ER) 1000 mg once daily for 5 days and immediate-release (IR) 500 mg twice daily for 7 days, in the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB).Patients and methods: This was a double-blind, randomized, parallel-group, multicenter study of ambulatory patients at least 40 years old with a presumptive diagnosis of ABECB, purulent sputum, and documented evidence of chronic obstructive pulmonary disease (COPD), including forced expiratory volume in one second (FEV1) < 70% of predicted value. Clinical cure, bacteriological cure, and target pathogen eradication rates were determined at a test-of-cure visit (study days 14–40). Safety was assessed based on the incidence of study drug-related adverse events.Results: A total of 485 patients were randomized (240 to ER and 245 to IR). Clinical cure rates were similar for evaluable patients treated with ER (84%, 157/187) and those treated with IR (84%, 172/204) (95% CI –7.9, 7.2). The bacteriological cure rates were 87% (82/94) and 89% (91/102), and the overall target pathogen eradication rates were 88% (107/122) and 89% (117/131) for the respective treatment groups. The incidence of adverse events was 13% (31/240) in the ER group and 18% (45/245) in the IR group. The rate of gastrointestinal adverse events was lower with ER (8%, 19/240) compared to IR (11%, 26/245). Clarithromycin ER-treated patients reported statistically significantly fewer adverse events due to abnormal taste than did clarithromycin IR-treated patients (3% and 8%, respectively, p = 0.012).Conclusion: Both once-daily, 5-day, short-course therapy with clarithromycin ER and 7-day, twice-daily therapy with clarithromycin IR were effective in resolving clinical signs/symptoms of ABECB and eradicating the causative pathogens, with no statistically significant difference in clinical cure rate between the treatment groups. Clarithromycin ER was better tolerated, causing fewer gastrointestinal adverse events and statistically significantly fewer reports of abnormal taste as compared with clarithromycin IR.

Gemifloxacin: a new, potent fluoroquinolone for the therapy of lower respiratory tract infections

The fluoroquinolone gemifloxacin has recently been approved for the treatment of acute bacterial exacerbations of chronic bronchitis and mild community acquired pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae. Owing to the increasing prevalence of multidrug-resistant S. pneumoniae, as well as resistance to other common pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, it is important to have new, potent antimicrobial agents for the treatment of these infections. Gemifloxacin is the most potent antimicrobial agent in vitro for S. pneumoniae, and has excellent activity against the other key pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, including the atypical microorganisms. The clinical trial outcomes of several studies that have evaluated gemifloxacin show a range of superior clinical or bacteriologic outcomes against several current antimicrobials, including levofloxacin, clarithromycin, trovafloxacin and ceftriaxone. The safety profile of gemifloxacin is similar to that of approved agents to treat acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, with a low discontinuation rate of 2.2%. A nonphototoxic rash (usually a mild, maculopapular rash) was observed in 2.8% of patients in clinical studies.

Efficacy and Safety of Azithromycin vs Levofloxacin in the Outpatient Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis

To compare the safety and efficacy of oral azithromycin and levofloxacin in the treatment of outpatients with acute bacterial exacerbations of chronic bronchitis (ABECB). Randomized, double-blinded, double-dummy, multicenter trial with 1:1 treatment allocation. Outpatient treatment setting. Two hundred thirty-five male or female outpatients between the ages of 35 and 75 years who had received a clinical diagnosis of ABECB. Blinded treatment with either oral azithromycin, 500 mg on day 1 and 250 mg per day for days 2 to 5, or, oral levofloxacin, 500 mg q24h for 7 days. Both treatments were well-tolerated, with the majority of adverse events being GI in nature. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24, the posttherapy visit, favorable responses were approximately 82% and 86%, respectively, for patients in the two treatment groups. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin. Despite increasing concerns over macrolide resistance and a higher incidence of Gram-negative pathogens, a standard 5-day course of oral azithromycin was clinically and bacteriologically equivalent to a 7-day course of oral levofloxacin in the treatment of patients with ABECB.

Les nouvelles fluoroquinolones dans les exacerbations aiguës de bronchite chronique

The role of the new class of fluoroquinolones in the treatment of acute bacterial exacerbations of chronic bronchitis involves the complex context of drug prescription in such situations. This is based on the probability of an infectious bacterial etiology, whether concerning a bronchial infection or pneumonia; and on the severity of the underlying respiratory disease and associated functional impairment. The most frequently encountered pathogenic agents infecting the respiratory tract are Streptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis, which have a common characteristic: a growing resistance to the usual antibiotics, in particular the aminopenicillins. The investigation carried out on anti-pneumococcal third-generation fluoroquinolones and their use in the treatment of bacterial exacerbations of chronic bronchitis has consisted of equivalence studies, aimed at demonstrating the superiority of one antibiotic compared to another. These investigations are characterized by a wide heterogeneity in populations, associated treatment and follow-up, and by a widespread uncertainty regarding the infectious nature of the exacerbation. The therapeutic success rate varies between 70 and 90%, with a frequently favorable tendency in terms of clinical and bacteriological efficacy recorded for the new fluoroquinolones. Chronic bronchitis is one of the most frequently encountered respiratory disorders. Its increasing prevalence renders it a major public health problem. The excessive prescription of antibiotics in cases of chronic bronchitis can have serious economic and environmental consequences. However, insufficient treatment of an acute bacterial exacerbation only aggravates the deterioration of respiratory function and negatively affects patient prognosis. In this pathological context, the possible role of fluoroquinolones that are active against pneumococci has been discussed in the light of recent clinical findings reported in the literature.

Review of cefditoren, an advanced-generation, broad-spectrum oral cephalosporin

Background: Cefditoren is an advanced-generation, broad-spectrum cephalosporin antibiotic approved for the treatment of acute bacterial exacerbation of chronic bronchitis (AECB), group A beta-hemolytic streptococcal pharyngotonsillitis, and uncomplicated skin/skin structure infections in adult and adolescent patients. Objective: This article briefly reviews the chemistry, antimicrobial activity, pharmacokinetics, efficacy, and safety of cefditoren. Methods: Literature was identified by a MEDLINE search (January 1985 to October 2001) of the medical literature, review of the English-language literature, reference lists within these articles, as well as data presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Results: Cefditoren has a broad spectrum of activity against many gram-negative and gram-positive aerobes, including Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefditoren is stable to hydrolysis by many common beta-lactamases. Cefditoren is rapidly absorbed (time to peak plasma concentration, ∼2–3 hours) from the gastrointestinal tract and is almost completely eliminated via renal clearance of unchanged drug. The terminal disposition half-life of the compound is ∼0.8 to 1.3 hours. Conclusions: Cefditoren is effective in the management of AECB (in regimens of 400 mg twice daily for 10 days) and acute maxillary sinusitis, pharyngotonsillitis due to S pyogenes, and uncomplicated skin/skin structure infections (in regimens of 200 mg twice daily for 10 days). Cefditoren possesses broad activity against common pathogens of the respiratory tract and skin and is stable in the presence of numerous beta-lactamases. Its pharmacokinetic properties, in conjunction with in vitro susceptibility data, document the feasibility of twice-daily dosing.

Traitement des exacerbations aiguës de bronchite chronique : efficacité et tolérance du céfuroxime axetil comparées à celles du cefpodoxime proxétil

A multicentre, randomised, open-label study was performed in 50 centres to demonstrate that the clinical efficacy of oral cefuroxime axetil 250 mg twice daily is equivalent to that of oral cefpodoxime proxetil 200 mg twice daily in a 10-day treatment of acute bacterial exacerbations of chronic bronchitis. Exacerbations were defined as sputum purulence and an increase in severity of at least two of the following symptoms: sputum volume, cough or dyspnea. Clinical efficacy, classified as success (cure or improvement) or failure, was assessed at the end of treatment (days 10–12) and at follow-up (days 30–40). A total of 268 patients (130 cefuroxime axetil, 138 cefpodoxime proxetil) were randomised between March and May 1999. All patients were assessed for safety analysis, Intent-To-Treat and Per-Protocol analysis. At the end of treatment, clinical success rates were equivalent with 95% (124/130) success in the cefuroxime axetil group and 92% (127/138) in the cefpodoxime proxetil group. At follow-up, equivalence was also demonstrated in the Intent-To-Treat analysis with clinical success rates of 94% and 91% for patients receiving cefuroxime axetil and cefpodoxime proxetil respectively. A secondary efficacy end point based on resolution of sputum purulence also provided equivalent success rates in both treatment groups (97% of patients treated with cefuroxime axetil and 96% of patients treated with cefpodoxime proxetil). A recurrence was observed for 2% of the cefuroxime axetil patients (2/130) and for 1% of cefpodoxime proxetil patients (1/138). Drug-related adverse events were reported in 2% of patients of cefuroxime axetil group (2/130) and 7% of patients of cefpodoxime proxetil (9/138). No unexpected side effect were observed. This study demonstrates that cefuroxime axetil 250 mg twice daily has an efficacy equivalent to cefpodoxime proxetil 200 mg twice daily in treatment of acute bacterial exacerbations of chronic bronchitis in adults. Both regimens were well tolerated.

Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis (ABECB) using a prospective, randomized, double-blind, parallel group trial.Between November 21, 1996 and April 7, 1998, 936 patients with acute exacerbations of chronic bronchitis (AECB) were enrolled at 56 centers across the United States of which 491 (52%) had ABECB (i.e. pretherapy pathogen).Patients were randomized to either oral moxifloxacin 400 mg administer once daily, for either 5 or 10 days, or clarithromycin 500 mg bid for 10 days. For the purpose of study blinding, the patients taking moxifloxacin received placebo to maintain uniform dosing.The main outcome measures were bacteriological response at the end of therapy (post-therapy days 0–6) and follow-up (7–17 days post-therapy) visits, as well as overall clinical response, clinical response at the end of therapy and clinical response at follow-up. Two patient populations were analyzed: efficacy-valid (i.e., those with a pretherapy pathogen) and intent-to-treat (i.e., all subjects that took drug).In 420 efficacy valid patients with a pretherapy organism, overall clinical resolution was 89% for 5 days moxifloxacin vs. 91% for 10 day moxifloxacin vs. 91% for 10 day clarithromycin. Bacteriological eradication rates at the end of therapy were 94% and 95% for 5-day moxifloxacin and 10-day moxifloxacin, respectively, and 91% for the clarithromycin group. Eradication rates at follow-up were 89% and 91% for 5-day moxifloxacin and 10-day moxifloxacin respectively, and 85% for the clarithromycin group. Among 926 intent-to-treat patients (312 5-day moxifloxacin, 302 10-day moxifloxacin and 312 clarithromycin), drug-related events were reported for 26%, 30% and 35%, respectively.Moxifloxacin 400 mg once daily, as a 5 or 10 day regimen, was found to be clinically and bacteriologically equivalent to 10 day clarithromycin for the treatment of ABECB. Given its favorable safety and tolerability profile, moxifloxacin administered once daily for 5 days may be as effective and a more convenient treatment than a standard course of clarithromycin for patients with ABECB.