Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telithromycin is a new ketolide antimicrobial, specifically developed for the treatment of community-acquired respiratory tract infections. It has a wide spectrum of antibacterial activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. It also has activity against atypical pathogens, such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. Telithromycin maintains activity against beta-lactam and macrolide-resistant respiratory tract pathogens and does not appear to induce cross-resistance to other members of the macrolide-lincosamide-streptogramin (MLS) group of antimicrobials. It demonstrates bactericidal activity against S. pneumoniae and H. influenzae and has a prolonged concentration-dependent post-antibiotic effect (PAE) in vitro. The drug has favourable pharmacokinetics following oral administration. It is well absorbed, achieves good plasma levels and is highly concentrated in pulmonary tissues and white blood cells. In clinical trials, telithromycin given orally at a dose of 800 mg once daily for 5 - 10 days was as effective as comparator antimicrobials for the treatment of adults with community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis and group A-beta-haemolytic streptococcal pharyngitis or tonsillitis. The adverse events and safety profile were similar to comparator antimicrobials. The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections.
 ...
PMID:Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections. 1117 47

Telithromycin is the first member of a new family of the macrolide-lincosamide-streptogramin-B (MLS(B)) class of antimicrobials, the ketolides. It has a good spectrum of activity against respiratory pathogens, including penicillin- and erythromycin-resistant pneumococci, as well as intracellular and atypical bacteria. Furthermore, it has a low potential to select for resistance or induce cross-resistance among other MLS(B) antimicrobials. At the recommended dosage of 800 mg orally once daily, telithromycin reaches maximal plasma concentrations of about 2 mg/L. It penetrates rapidly into bronchopulmonary, tonsillar, sinus and middle ear tissues and/or fluids and achieves high concentrations at sites of infection. It also concentrates within polymorphonuclear neutrophils. In clinical trials in patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) or pharyngitis/tonsillitis caused by group A beta-haemolytic streptococci, telithromycin 800 mg once daily achieved clinical cure rates of 86 to 95%. In acute maxillary sinusitis (AMS), cure rates were 73 to 91%. A 7- to 10-day regimen of telithromycin was as effective as a 10-day course of amoxicillin 1000 mg 3 times daily, clarithromycin 500 mg twice daily or a 7- to 10-day course of trovafloxacin 200 mg once daily for treating CAP. A 5-day regimen of telithromycin was as effective as a 10-day regimen of cefuroxime axetil 500 mg twice daily or amoxicillin/clavulanic acid 500/125 mg 3 times daily in AECB. A 5-day regimen of telithromycin was as effective as a 10-day regimen of clarithromycin 250 mg twice daily or phenoxymethylpenicillin 500 mg 3 times daily in pharyngitis/tonsillitis, or a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg 3 times daily in patients with AMS. Telithromycin was well tolerated across all patient populations. Adverse events associated with telithromycin were generally mild to moderate in intensity and seldom led to treatment discontinuation. The most frequent adverse events were diarrhoea (13.3%) and nausea (8.1%). Other adverse events included dizziness and vomiting.
 ...
PMID:Telithromycin. 1139 13

Community-acquired pneumonia (CAP) is a common disorder that has been the focus of a major international research effort to define its epidemiology, etiology and management. The microbial etiology of CAP is complex and severity assessment is important in identifying at-risk populations as well as defining therapeutic strategies. Laboratory investigations rarely influence initial therapy, which remains empirical. Guidelines have been developed in many countries in response to the need to optimize management and outcomes. However, many of these guidelines have been based on expert opinion rather than robust evidence. New evidence-based guidelines have been developed that take into account disease severity, the local distribution of pathogens and their likely susceptibility to antimicrobials, and that include newer treatment options. Macrolide and fluoroquinolone antimicrobials feature heavily in these new treatment recommendations. Promising new therapies continue to emerge that may offer advantages over fluoroquinolones and macrolides, in particular with regard to the problem of resistance. Of these, the ketolides are of special interest. Telithromycin, the first ketolide antibacterial, has been evaluated in the treatment of > 700 patients with CAP. A once-daily oral dose of telithromycin 800 mg for 7-10 days produces clinical and bacteriological success rates > 90% and equivalent to standard comparator agents, whilst maintaining efficacy against resistant pathogens.
 ...
PMID:Community-acquired pneumonia: the evolving challenge. 1152 60

Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp. and Chlamydia spp. form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP). The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens. Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens. Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established. This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.
 ...
PMID:Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens. 1156 73

The ketolides represent a new subclass of antibiotics among the macrolide-lincosamide-streptogramin group. Telithromycin, the first ketolide to be awarded approvable status for clinical use, demonstrates in vitro activity against community-acquired respiratory pathogens including penicillin- and erythromycin-resistant Streptococcus pneumoniae. An extended half-life permits once-daily oral administration. Telithromycin is a substrate for cytochrome P450 (CYP) 3A4 and also inhibits drugs metabolized by CYP3A4. A relatively high frequency of mild-to-moderate gastrointestinal adverse effects has been reported. Similar clinical and microbiologic efficacy has been demonstrated with oral dosing in comparative clinical trials for community-acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, and pharyngitis. Although limited data on penicillin-resistant S. pneumoniae and erythromycin-resistant Streptococcus pyogenes are available from clinical trials, this drug appears promising for respiratory infections caused by these pathogens.
 ...
PMID:Telithromycin: an oral ketolide for respiratory infections. 1160 67

Among adults, acute sinusitis, tonsillitis/pharyngitis, community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are the most commonly encountered respiratory tract infections (RTIs) in the community. Empiric antibacterial therapy is the most widely used approach for the treatment of such infections. The appropriate antibacterial requires consideration of a number of patient-, pathogen- and drug-related factors. One additional factor is the global spread of resistance among common respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, which limits the utility of existing antibacterials. Telithromycin (HMR 3647), the first of a new family of antibacterials, the ketolides, was designed specifically to provide optimal therapy for community-acquired RTIs. This agent, which has a broad spectrum of antibacterial activity against common respiratory pathogens (including resistant strains and atypical/intracellular organisms), has been clinically and bacteriologically evaluated against gold-standard comparators in a series of phase III clinical trials. The results of these studies demonstrate that telithromycin, at a dosage of 800 mg once daily, is an effective, well-tolerated agent for the treatment of the most commonly encountered community-acquired RTIs. Moreover, telithromycin meets the challenge of increasing antibacterial resistance. High rates of clinical cure and bacteriologic eradication were achieved, even in patients infected with problematic resistant pathogens such as penicillinG- and macrolide-resistant S. pneumoniae. In summary, telithromycin represents a promising new antibacterial for the treatment of community-acquired RTIs. With high efficacy and bacterial eradication rates, good tolerability and convenient once-daily administration, telithromycin therapy should result in increased patient compliance and improved outcomes, thereby minimizing the risk of developing antibacterial resistance.
 ...
PMID:Clinical management of respiratory tract infections in the community: experience with telithromycin. 1178 52

The ketolide telithromycin (HMR-3647; Ketek), a derivative of clarithromycin, has been launched by Aventis Pharma (formerly Hoechst Marion Roussel) for the treatment of respiratory tract infections with gram-positive or gram-negative cocci, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, intracellular pathogens, atypical microorganisms, toxoplasma or anaerobic bacteria. By May 2001, filings in the US and EU had been completed and a filing in Japan was expected to take place in the fourth quarter of 2001. In July 2001, telithromycin was granted marketing authorization by the EC for the treatment of community-acquired respiratory tract infections, including those caused by bacteria resistant to commonly used antibiotics. In October 2001, the product was launched in Germany. In March 2000, telithromycin was submitted to the US FDA and the EMEA, under the EU centralized approval procedure, for approval for the treatment of community-acquired pneumonia (CAP), acute sinusitis, acute exacerbations of chronic bronchitis and tonsillitis/pharyngitis. The company had expected to launch the product in early 2001. The CPMP issued a positive opinion for all four indications on April 23 2001. In September 2001, the company indicated that it expected the product to be launched in Japan in 2002. The FDA's Anti-infectives Advisory Committee was due to review telithromycin for all the submitted indications on January 29 2001; however, this was postponed. This postponement was thought to be at Aventis' request in order to discuss the potential for a resistant pneumococcal infection labeling which would boost product sales. The revised date for the meeting was April 26 2001, at which the Anti-Infective Drugs Advisory Committee of the FDA recommended approval of telithromycin for the treatment of CAP in patients 18 years of age or older. The committee failed to recommend approval for the use of the drug for the remaining three indications for which it was filed, citing concerns over potential cardiovascular risk and liver toxicity; at this time, the company was in active discussions with the FDA regarding approval of the remaining three indications. An approvable letter for CAP, acute bacterial exacerbations of chronic bronchitis and acute bacterial sinusitis was received by the company in June 2001; Aventis also received a non-approvable letter for the treatment of tonsillitis/pharyngitis at this time. In April 1999, ABN Amro predicted annual sales of DM 50 million in 2001, rising to DM 100 million in 2002. In February 1999, Lehman Brothers estimated a 70% probability that this ketolide would come to market. The analysts also estimated a launch date of 2001, with peak sales of US $700 million in 2009. Analysts Merrill Lynch predicted in September 200, that the product would be launched by 2001, with sales of euro 50 million in that year, rising to euro 284 million in 2004. Deutsche Bank predicted in August 2001, that sales of the product would reach euro 5 million in 2001, rising to euro 300 million in 2005. Analysts at Merrill Lynch predicted in November 2001, that the product would be resubmitted in the US in mid-2002, and would make sales of US $5 million in 2001, rising to US $250 million in 2004.
 ...
PMID:Telithromycin. Aventis Pharma. 1189 30

Ketolides are a new class of macrolides designed particularly to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A, and retain the erythromycin macrolactone ring structure as well as the D-desosamine sugar attached at position 5. The defining characteristic of the ketolides is the removal of the neutral sugar, L-cladinose from the 3 position of the ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. The ketolides presently under development additionally contain an 11, 12 cyclic carbamate linkage in place of the two hydroxyl groups of erythromycin A and an arylalkyl or an arylallyl chain, imparting in vitro activity equal to or better than the newer macrolides. Telithromycin is the first member of this new class to be approved for clinical use, while ABT-773 is presently in phase III of development. Ketolides have a mechanism of action very similar to erythromycin A from which they have been derived. They potently inhibit protein synthesis by interacting close to the peptidyl transferase site of the bacterial 50S ribosomal subunit. Ketolides bind to ribosomes with higher affinity than macrolides. The ketolides exhibit good activity against Gram-positive aerobes and some Gram-negative aerobes, and have excellent activity against drug-resistant Streptococcus pneumoniae, including macrolide-resistant (mefA and ermB strains of S. pneumoniae). Ketolides such as telithromycin display excellent pharmacokinetics allowing once daily dose administration and extensive tissue distribution relative to serum. Evidence suggests the ketolides are primarily metabolised in the liver and that elimination is by a combination of biliary, hepatic and urinary excretion. Pharmacodynamically, ketolides display an element of concentration dependent killing unlike macrolides which are considered time dependent killers. Clinical trial data are only available for telithromycin and have focused on respiratory infections including community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis and streptococcal pharyngitis. Bacteriological and clinical cure rates have been similar to comparators. Limited data suggest very good eradication of macrolide-resistant and penicillin-resistant S. pneumoniae. As a class, the macrolides are well tolerated and can be used safely. Limited clinical trial data suggest that ketolides have similar safety profiles to the newer macrolides. Telithromycin interacts with the cytochrome P450 enzyme system (specifically CYP 3A4) in a reversible fashion and limited clinically significant drug interactions occur. In summary, clinical trials support the clinical efficacy of the ketolides in upper and lower respiratory tract infections caused by typical and atypical pathogens including strains resistant to penicillins and macrolides. Considerations such as local epidemiology, patterns of resistance and ketolide adverse effects, drug interactions and cost relative to existing agents will define the role of these agents. The addition of the ketolides in the era of antibacterial resistance provides clinicians with more options in the treatment of respiratory infections.
 ...
PMID:The ketolides: a critical review. 1214 46

Infections of the lower respiratory tract, such as community-acquired pneumonia (CAP) and acute bacterial exacerbations of chronic bronchitis (AECB), comprise the more serious respiratory tract infections (RTIs), and are associated with considerable morbidity and mortality, particularly in groups such as the very young, the elderly and those with co-morbid illness. Up to 80% of community-acquired RTIs are caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and are usually treated empirically. However, antibacterial resistance among common respiratory tract pathogens currently threatens the usefulness of existing therapies. The new ketolide antibacterial, telithromycin, has been developed specifically to provide optimal empirical treatment of community-acquired RTIs in the face of widespread antibacterial resistance. Telithromycin 800 mg once-daily offers efficacy equivalent to currently available antibacterials in the treatment of lower RTIs. Moreover, telithromycin demonstrates excellent activity in the treatment of CAP and AECB patients at risk for increased morbidity and mortality, including elderly patients, those with severe infections, and those with CAP complicated by pneumococcal bacteraemia. Telithromycin is also extremely effective in the treatment of patients with lower RTIs caused by atypical and intracellular pathogens (such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila [Chlamydia] pneumoniae--increasingly recognized as important aetiological agents of RTIs, particularly CAP), or by pathogens resistant to beta-lactams and macrolides. Telithromycin therefore represents a promising new agent for the empirical treatment of community-acquired RTIs.
 ...
PMID:Clinical efficacy of new antibacterial therapies in at-risk populations. 1215 Apr 92

Telithromycin, the first ketolide antibacterial, was developed for the treatment of community-acquired respiratory tract infections. This multicenter, open-label, uncontrolled study assessed the efficacy and safety of 800 mg, once-daily telithromycin in adults with community-acquired pneumonia (CAP). Based on bacteriologic eradication rates, telithromycin was shown to be effective for the treatment of CAP. Telithromycin was generally well tolerated, with gastro-intestinal adverse events observed most frequently (diarrhea 4/218 [1.8%], nausea 4/218 [1.8%], vomiting 5/218 [2.3%]). These results were consistent with those observed in randomized, active-controlled studies.
 ...
PMID:Efficacy and safety of telithromycin in community-acquired pneumonia. 1248 5


1 2 3 4 5 Next >>