ru-66647 and Sinusitis

Topics: Anti-Bacterial Agents; Bronchitis; Clinical Trials as Topic; Humans; Ketolides; Macrolides; Pharyngitis; Pneumonia, Bacterial; Respiratory Tract Infections; Sinusitis; Tonsillitis

Telithromycin, the first member of the ketolide antibacterials, has good activity against community-acquired respiratory pathogens, including multiple-drug-resistant strains of Streptococcus pneumoniae. Telithromycin 800 mg once daily has been US FDA approved for the treatment of acute bacterial sinusitis (ABS; treatment duration 5 days), acute bacterial exacerbations of chronic bronchitis (AECB; 5 days) and mild-to-moderate community-acquired pneumonia (CAP; 7-10 days). In patients with CAP, telithromycin was as effective as amoxicillin 1000 mg three times daily for 10 days, clarithromycin 500 mg twice daily for 10 days or trovafloxacin 200 mg once daily for 7-10 days. In patients with AECB, telithromycin was as effective as a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg three times daily, cefuroxime axetil 500 mg twice daily or clarithromycin 500 mg twice daily. In patients with ABS, telithromycin was as effective as a 10-day course of amoxicillin/clavulanic acid 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily. Telithromycin was generally well tolerated and most adverse events were of mild-to-moderate severity and transitory. The most common adverse events with telithromycin were diarrhoea and nausea (10.8% and 7.9% of 2702 patients in clinical trials); these events occurred in 8.6% and 4.6% of 2139 comparator-treated patients.

Topics: Anti-Bacterial Agents; Biological Availability; Bronchitis, Chronic; Clinical Trials as Topic; Community-Acquired Infections; Humans; Ketolides; Macrolides; Metabolic Clearance Rate; Pneumonia; Sinusitis; Treatment Outcome

This study compared the clinical efficacy, time to symptom resolution, and tolerability of a 5-day regimen of telithromycin with a 10-day regimen of high-dose amoxicillin-clavulanate in acute bacterial sinusitis (ABS).. In this multinational (41 centers in Canada, Germany, Greece, Portugal, and Turkey), open-label, noninferiority study, patients >/=18 years old (n=298) with a clinical (>7 days' symptoms) and radiological (air/fluid level, total opacification, mucosal thickening >/=10 mm) diagnosis of ABS were randomized to receive telithromycin 800 mg once daily for 5 days or amoxicillin-clavulanate 875/125 mg twice daily for 10 days. Clinical efficacy and tolerability were assessed at the test-of-cure visit (days 17-21). Time to symptom resolution was based on patients' daily diary assessment of individual symptoms.. The per-protocol clinical success rate (primary endpoint) with telithromycin (88.6% (109/123)) was noninferior to that with amoxicillin-clavulanate (88.8% (111/125)) (95% confidence interval: -8.9 to 8.5). In the modified intention-to-treat (mITT) population, the median time for 50% reduction of total symptom scores was significantly shorter for telithromycin (4 days) vs. amoxicillin-clavulanate (5 days; p=0.044); median times for 75% reduction of total symptom scores were: telithromycin, 7 days; amoxicillin-clavulanate, 8 days (p=0.115). The median time for reduction of total symptom scores to the absent/very mild category (mITT population) was 6 days for telithromycin vs. 8 days for amoxicillin-clavulanate (p=0.04). All treatment-emergent adverse events (TEAEs) were mostly gastrointestinal and occurred in 20.7% (30/145) of telithromycin-treated patients vs. 31.8% (47/148) of amoxicillin-clavulanate-treated patients (p=0.034). One serious AE was reported in the telithromycin group, but it was considered not to be related to treatment.. This open-label, randomized study demonstrated that treatment of ABS with telithromycin resulted in comparable clinical efficacy, shorter times to symptom resolution, and fewer total TEAEs than treatment with amoxicillin-clavulanate.

Topics: Acute Disease; Adult; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactam Resistance; Drug Administration Schedule; Female; Haemophilus influenzae; Humans; Ketolides; Male; Middle Aged; Outcome Assessment, Health Care; Quality of Life; Sinusitis; Streptococcus pneumoniae; Surveys and Questionnaires

Telithromycin has a broad spectrum of activity against respiratory tract pathogens including penicillin- and macrolide-resistant streptococci. The aim of the study was to investigate the penetration of telithromycin into nasal tissue following a single oral dose of 800 mg.. A total of 29 patients undergoing rhinosurgery for chronic sinusitis were evaluated. Samples of blood, nasal mucus, nasal mucosa and ethmoid bone were collected during surgery in groups of 5-6 patients after 3, 6, 9, 15 and 24 h following a single oral dose of 800 mg telithromycin. Drug concentrations were determined by HPLC with fluorimetric detection.. The highest telithromycin concentrations were observed after 3 h in plasma as well as in all tissues sampled. The mean plasma concentrations were 0.73 mg/L in the 3 h group and 0.02 mg/L in the 24 h group. The concomitant tissue concentrations were higher. The tissue penetration, expressed by the ratio of the area under the concentration-time curve in tissue versus plasma, was 1.0 for nasal mucus, 5.9 for nasal mucosa and 1.6 for ethmoid bone.. Telithromycin achieved tissue concentrations that were generally above the MIC(90) for common pathogens in upper respiratory tract infections. These results indicate that telithromycin diffuses rapidly into the nasal tissues and achieves high and prolonged concentrations in nasal mucosa and ethmoid bone.

Topics: Adult; Aged; Anti-Bacterial Agents; Area Under Curve; Ethmoid Bone; Female; Humans; Ketolides; Male; Middle Aged; Nasal Mucosa; Sinusitis

To compare the clinical and bacteriologic efficacy and safety of short-duration treatment with telithromycin given for 5 days with moxifloxacin given for 10 days in adults with acute bacterial rhinosinusitis (ABRS).. In this prospective, double-blind, parallel-group, randomized, multicenter study, adult patients (N = 349) with ABRS were randomized to oral telithromycin (800 mg once daily for 5 days) or to oral moxifloxacin (400 mg once daily for 10 days) and followed for 31 to 36 days. Clinical outcome was determined by the investigator at the posttherapy/test of cure (TOC) visit. Bacteriologic outcome was determined by comparing cultures taken at the pretreatment visit with cultures obtained at the posttherapy/TOC visit. The primary objective was to demonstrate equivalence of clinical cure rates in the per-protocol population between treatment groups at the posttherapy/TOC visit.. Clinical success at TOC (primary endpoint) was achieved in 87.4% of patients in the telithromycin group compared with 86.9% for moxifloxacin (per-protocol patients; 0.5% difference between treatment groups; 95% confidence interval [CI], -8.1, 9.2; P = 0.8930). The bacteriologic success rates were 94.1% and 93.9%, respectively (0.2% difference between treatment groups; 95% CI, -14.2, 14.5; P = 0.9734). Overall treatment-emergent adverse events for both drugs (mostly gastrointestinal) were mild to moderate in intensity.. The clinical and bacteriologic efficacy of telithromycin 800 mg once daily for 5 days was equivalent to that of moxifloxacin 400 mg once daily for 10 days, establishing telithromycin as an important treatment option for ABRS.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Aza Compounds; Bacterial Infections; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Humans; Ketolides; Macrolides; Male; Middle Aged; Moxifloxacin; Prospective Studies; Quinolines; Rhinitis; Sinusitis; Time Factors

Quantitative methods have been proposed to assess and compare the benefit-risk balance of treatments. Among them, multicriteria decision analysis (MCDA) is a popular decision tool as it permits to summarise the benefits and the risks of a drug in a single utility score, accounting for the preferences of the decision-makers. However, the utility score is often derived using a linear model which might lead to counter-intuitive conclusions; for example, drugs with no benefit or extreme risk could be recommended. Moreover, it assumes that the relative importance of benefits against risks is constant for all levels of benefit or risk, which might not hold for all drugs. We propose Scale Loss Score (SLoS) as a new tool for the benefit-risk assessment, which offers the same advantages as the linear multicriteria decision analysis utility score but has, in addition, desirable properties permitting to avoid recommendations of non-effective or extremely unsafe treatments, and to tolerate larger increases in risk for a given increase in benefit when the amount of benefit is small than when it is high. We present an application to a real case study on telithromycin in Community Acquired Pneumonia and Acute Bacterial Sinusitis, and we investigated the patterns of behaviour of Scale Loss Score, as compared to the linear multicriteria decision analysis, in a comprehensive simulation study.

Topics: Acute Disease; Anti-Bacterial Agents; Community-Acquired Infections; Computer Simulation; Decision Support Techniques; Humans; Ketolides; Pneumonia; Risk Assessment; Sinusitis

Topics: Adverse Drug Reaction Reporting Systems; Anti-Bacterial Agents; Bronchitis, Chronic; Chemical and Drug Induced Liver Injury; Drug Approval; Humans; Ketolides; Risk Assessment; Sinusitis; United States; United States Food and Drug Administration

Topics: Acute Disease; Anti-Bacterial Agents; Bronchitis, Chronic; Community-Acquired Infections; Drug Approval; Drug Labeling; Humans; Ketolides; Patient Education as Topic; Pneumonia, Bacterial; Sinusitis; United States; United States Food and Drug Administration

Telithromycin, the first ketolide antimicrobial agent available in the United States, is related to the macrolide class of antibiotics. Reports of immediate-type hypersensitivity reactions with macrolides or ketolides are rare overall.. To describe a patient with a severe, apparent mast cell-mediated reaction to telithromycin.. A 54-year-old woman with a history of hypertension was prescribed telithromycin by her primary care physician for presumed bacterial sinusitis. Shortly after ingesting the first dose of telithromycin she developed severe shortness of breath, wheezing, and angioedema. Her allergic history was significant for the development of a maculopapular rash after taking sulfonamide antibiotics, but she had received erythromycin and azithromycin in the past with no adverse effects. She was intubated with difficulty and was treated with epinephrine, diphenhydramine, and corticosteroids. The patient made a full recovery.. Although not confirmed, the patient's severe symptoms were anaphylactoid and were ascribed to an immediate-type hypersensitivity reaction to telithromycin. No other causative agents, including other drugs, foods, and environmental exposures, were implicated in this case. Her history of tolerability to macrolide antibiotics is of interest considering the chemical similarities between these drugs and telithromycin.. To our knowledge, this is the first reported case of a severe, immediate-type hypersensitivity reaction to telithromycin. Physicians prescribing this drug should be aware of this rare but serious effect.

Topics: Adrenal Cortex Hormones; Anaphylaxis; Anti-Allergic Agents; Anti-Bacterial Agents; Azithromycin; Bronchodilator Agents; Diphenhydramine; Epinephrine; Female; Humans; Hypertension; Ketolides; Macrolides; Middle Aged; Sinusitis

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Conflict of Interest; Drug Industry; Humans; Ketolides; Periodicals as Topic; Practice Guidelines as Topic; Rhinitis; Sinusitis; United States

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.

Topics: Anti-Bacterial Agents; Bronchitis, Chronic; Community-Acquired Infections; Drug Approval; Drug Labeling; Drug Utilization Review; Humans; Insurance Claim Reporting; Ketolides; Pneumonia, Bacterial; Retrospective Studies; Risk Assessment; Sinusitis; United States; United States Food and Drug Administration

Telithromycin is the first ketolide anti bacterial approved for treating community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis in adults. The purpose of this article is to review the main pharmacokinetic properties of telithromycin and their application to the treatment of these infections.. Sources of information were identified through a Medline search (up to March 2005).. The absolute oral bioavailability of telithromycin is approximately 57%, which is unaffected by food intake. At the recommended 800 mg once-daily oral dosing regimen, telithromycin reaches a steady-state concentration of approximately 2 microg/mL in plasma and has an elimination half-life of approximately 10 hours. Telithromycin shows extensive tissue distribution and penetrates effectively into bronchopulmonary tissue and epithelial lining fluid. Since elimination of telithromycin occurs via multiple pathways--the highest proportion (70%) through metabolism--impairment of a single pathway has a limited impact on telithromycin exposure. Dose adjustments are unnecessary in elderly patients or in individuals with hepatic impairment or mild to moderate renal impairment. A reduced dose could be recommended in patients with severe renal impairment. Telithromycin is metabolized primarily in the liver, approximately half of which is via the cytochrome P450 (CYP) 3A4 system. Telithromycin AUC(0-24 h) increased by 1.5- to 2.0-fold in the presence of itraconazole and ketoconazole. Administration of telithromycin with drugs metabolized via CYP3A4 may result in increased exposure to the co-administered drug, as shown for simvastatin (5.3-fold) and midazolam (6-fold). Co-administration of telithromycin minimally increases (1.2- to 1.4-fold) exposure to theophylline, digoxin, and metoprolol. Although telithromycin does not affect the pharmacokinetics of warfarin, consideration should be given to monitoring prothrombin times/INR in patients receiving telithromycin and oral anticoagulants simultaneously.. Overall, the pharmacokinetic/pharmaco dynamic properties of telithromycin indicate that this ketolide antibacterial is a valuable and convenient treatment option for community-acquired respiratory tract infections.

Topics: Aged; Anti-Bacterial Agents; Biological Availability; Bronchitis; Community-Acquired Infections; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Ketolides; Kidney Diseases; Pneumonia; Respiratory Tract Infections; Sinusitis

To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections.. The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin.. In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively.. High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

Topics: Acute Disease; Adolescent; Adult; Bacteria; Bronchitis; Chronic Disease; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Community-Acquired Infections; Female; Humans; In Vitro Techniques; Ketolides; Macrolides; Male; Microbial Sensitivity Tests; Pneumonia; Randomized Controlled Trials as Topic; Sinusitis

Topics: Acetylation; Analgesics, Non-Narcotic; Antacids; Anti-Bacterial Agents; Clarithromycin; Cytochrome P-450 Enzyme System; Digitalis Glycosides; Digoxin; Drug Interactions; Ergotamine; Ergotism; Female; Humans; Hypolipidemic Agents; Ketolides; Macrolides; Middle Aged; Migraine Disorders; Muscular Diseases; Risk Factors; Sinusitis; Vasoconstrictor Agents

Topics: Anti-Bacterial Agents; Bronchitis; Community-Acquired Infections; Health Policy; Humans; Ketolides; Macrolides; Pneumonia; Sinusitis; United States; United States Food and Drug Administration