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

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.
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PMID:Telithromycin. Aventis Pharma. 1189 30

Several new fluoroquinolones have been marketed since the late 1990s. Fluoroquinolones are an effective treatment for most community-acquired respiratory tract infections, including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. However, other antibiotics, including beta-lactams, macrolides, tetracyclines and trimethoprim-sulfamethoxazole, are also effective against these respiratory infections. From a managed care perspective, it is the subtle differences between the drugs in the eradication of bacterial pathogens, adverse effects, dose regimens, compliance issues, bacterial resistance and cost that determine the best choice for the management of pneumonia, sinusitis or exacerbations of chronic bronchitis. The potential for bacterial resistance is perhaps the only significant barrier to extensive fluoroquinolone use in community-acquired respiratory tract infections. Cost-effectiveness must be balanced with quality care, both from an individual perspective and that of the greater society.
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PMID:Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections. 1218 18

Respiratory tract infections have an important clinical and economic impact and they are the most common indication for antibiotic use in outpatient practice. This prospective, multicenter non-controlled trial assessed the efficacy and safety of gatifloxacin in the treatment of community-acquired respiratory tract infections. Patients were treated with a daily oral dose of gatifloxacin 400 mg for 7-14 days. The diagnosis of respiratory infection was made based on the clinical condition and/or radiologic findings. A total of 5,044 adult patients with community-acquired respiratory infections was treated with gatifloxacin in different centers in Brazil between March 1, 2001, and October 31, 2001. Among the 5,044 patients treated, 1,501 patients (29.76%) had community-acquired pneumonia, 756 (14.99%) had acute exacerbation of chronic bronchitis and 2,787 (55.25%) had acute sinusitis. Of the total of patients treated, 3,607 (71.51%) were considered cured, 1,261 (25%) progressed with some clinical improvement, 28 (0.56%) presented a relapse, 56 (1.11%) failed to treatment and 92 (1.82%) were unable to be evaluated. Adverse events were described in 634 (12.57%) patients. The most common adverse events were: nausea (2.24%); dyspepsia (1.86%); diarrhea (0.79%); change in taste (0.46%); insomnia and irritability (0.22%); dizziness (0.77%); headache (0.42%); allergic reaction (0.18%); Central Nervous System alterations insomnia, agitation, anxiety (0.46%). This study showed that the treatment of respiratory tract infections with gatifloxacin was safe and efficient and had a low incidence of adverse events.
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PMID:Treatment of adults with community-acquired respiratory tract infections: results of a multicentric clinical trial with gatifloxacin. 1220 81

Recently FDA-approved fluoroquinolones like gatifloxacin possess enhanced activity against Gram-positive pathogens such as Streptococcus pneumoniae. However, experience with adverse events among previously used fluoroquinolones has led to expanded post-marketing investigations of clinical efficacy and safety. An open-label gatifloxacin trial was initiated in early 2000, using 2795 (>15000 enrolled cases) primary care providers for treatment of community-acquired respiratory tract infections (CARTI) such as community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (ABECB), acute sinusitis. Microbiology specimens and sputum slides were referred to a reference laboratory, pathogens identified and reference antimicrobial susceptibility tests performed. Results were classified by infection site, geographic census region and patient profile/demographics. The most frequent pathogens were: for CAP (n = 384)-S. pneumoniae (37%) > Hemophilus influenzae (31%) > Moraxella catarrhalis (13%); for ABECB (528)-H. influenzae (37%) > M. catarrhalis (26%) > S. pneumoniae (17%); and for sinusitis (2691)-M. catarrhalis (29%) > H. influenzae (24%) > S. pneumoniae (17%). H. parainfluenzae (ABECB) and S. aureus (sinusitis) were also commonly isolated. CAP S. pneumoniae isolates had significantly less high-level resistance (5% at > or =2 micro g/ml) than those isolates from ABECB or sinusitis (13-15%). United States census zone differences in S. pneumoniae resistance were identified (greatest in West or East South Central, South Atlantic). S. pneumoniae macrolide resistance was high (23-33%) and H. influenzae clarithromycin susceptibility was only 56-62%. beta-lactamase rates in H. influenzae and M. catarrhalis were 21-29% and 88-92%, respectively. Only one S. pneumoniae was not susceptible to gatifloxacin, and this new fluoroquinolone was fourfold more potent than levofloxacin (MIC(50,) 0.25 vs. 1 micro g/ml). This Phase IV surveillance trial (TeqCES) confirmed the clinical importance of S. pneumoniae, H. influenzae and M. catarrhalis in CARTI, and high fluoroquinolone potency/spectrum (>97% susceptible). beta-lactams and macrolides continue to be compromised by increasing resistances in pathogens isolated in these monitored primary care settings.
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PMID:Gatifloxacin phase IV surveillance trial (TeqCES study) utilizing 5000 primary care physician practices: report of pathogens isolated and susceptibility patterns in community-acquired respiratory tract infections. 1237 36

Community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute sinusitis are among the most common bacterial infections encountered in clinical practice. Pathogens frequently associated with these infections include Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Unfortunately, resistance to antimicrobials commonly used for the treatment of these infections is increasing, limiting the clinical efficacy of these agents. Fluoroquinolones offer several advantages over other classes of antimicrobials used for the treatment of community-acquired respiratory tract infections. In general, fluoroquinolones have excellent in vitro activity against common respiratory pathogens, including some drug-resistant strains of S. pneumoniae. Microbial resistance to the newer fluoroquinolones is relatively uncommon, currently occurring in approximately 1% of clinical isolates in North America. Fluoroquinolones currently in clinical development may offer additional benefits over the marketed agents because they maintain good potency against isolates of S. pneumoniae displaying resistance to older quinolones (i.e., ofloxacin or ciprofloxacin) and may have a lower potential to engender resistance. This article reviews the in vitro activity of several newer fluoroquinolones, including agents currently in clinical development, against common respiratory pathogens, including antimicrobial-resistant strains. The mechanisms and prevalence of resistance of beta-lactam antimicrobials, macrolides, and fluoroquinolones also are reviewed.
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PMID:Microbiology of newer fluoroquinolones: focus on respiratory pathogens. 1249 66

(1) Macrolides are an alternative to beta-lactam agents for treating uncomplicated community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis and throat infections. The choice of macrolides is based mainly on the risk of interactions, which is lowest with spiramycin. (2) Telithromycin is a macrolide antibiotic derived from erythromycin. It was first marketed in France in 2002, for the above indications. (3) Telithromycin is no more effective than the antibiotics with which it has been compared, namely amoxicillin and clarithromycin in non life-threatening pneumonia; amoxicillin-clavulanate and cefuroxime axetil in acute exacerbations of chronic bronchitis and acute sinusitis; and clarithromycin and phenoxymethylpenicillin (penicillin V) in pharyngotonsillitis. (4) In clinical trials, telithromycin was not more effective than comparator antibiotics on infections thought to be due to pneumococcal strains resistant to penicillin and/or erythromycin. Cases of erythromycin cross-resistance have been observed. (5) The adverse effects of telithromycin are the same as those of other macrolides, mainly gastrointestinal disturbances, headache, dizziness, and hepatotoxicity. Telithromycin also carries a risk of torsades de pointes, and seems to cause more visual problems than other macrolides. (6) Telithromycin inhibits cytochrome P450 isoenzymes, so there is a high risk of drug interactions. (7) In practice, spiramycin remains the standard option when a macrolide is indicated for the treatment of common ENT and pulmonary infections.
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PMID:Telithromycin: new preparation. A needless addition to the other macrolides. 1260 73

(1) The risk-benefit ratio of antibiotic therapy in exacerbations of chronic bronchitis is uncertain. If an antibiotic is considered, fluoroquinolones are at best second-line options, after betalactam agents such as amoxicillin, and macrolides. (2) For community-acquired pneumonia the first-line antibiotics are betalactam agents such as amoxicillin, and macrolides. Patients with severe disease should receive combination therapy with a betalactam and a macrolide or a fluoroquinolone. (3) Acute sinusitis generally resolves spontaneously. If an antibiotic is prescribed, fluoroquinolones are at best second-line options, after betalactam agents such as amoxicillin, and macrolides. The value of systemic antibiotic therapy is also controversial in chronic sinusitis and chronic otitis media; once again, fluoroquinolones are not agents of first choice. (4) Fluoroquinolones share many adverse effects, especially neuropsychiatric, cutaneous, tendon, and cardiac involvement. They can also damage cartilage in children. They are contraindicated in pregnant women. They potentiate oral anticoagulants.
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PMID:Fluoroquinolones in ambulatory ENT and respiratory tract infections: rarely appropriate. 1260 5

The incidence of community-acquired respiratory tract infections caused by Streptococcus pneumoniae exhibiting antibacterial resistance has increased dramatically in recent years. Telithromycin is the first of a new class of antibacterials, the ketolides, which have been developed specifically to provide effective treatment for these infections. Data were analysed from 3935 patients who had participated in one Japanese Phase II study and 11 US/global Phase III studies in three indications: community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Patients received either telithromycin 800 mg once daily or a comparator antibacterial. S. pneumoniae isolates considered to be causative for infection were tested for susceptibility to penicillin G and erythromycin A. In per-protocol analyses, telithromycin showed a high level of clinical efficacy against S. pneumoniae, with clinical cure rates of 92.8% for all isolates, 91.7% for those with reduced susceptibility to penicillin G and 86.0% for those with reduced susceptibility to erythromycin A. Bacterial eradication rates were consistent with the clinical outcomes. High rates of clinical cure and bacterial eradication were also observed for infections caused by isolates demonstrating high-level resistance to erythro-mycin A [MICs >/= 512 mg/L: 100% (13/13) clinical cure, 100% (13/13) bacterial eradication]. These results support the use of telithromycin as a first-line oral therapy for the treatment of community-acquired respiratory tract infections caused by S. pneumoniae with reduced susceptibility to penicillin G and erythromycin A.
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PMID:Community-acquired respiratory tract infections caused by resistant pneumococci: clinical and bacteriological efficacy of the ketolide telithromycin. 1265 63

Telithromycin, the first ketolide antibiotic to undergo clinical development, has been specifically designed to treat community-acquired respiratory tract infections, including those caused by resistant pathogens. Like macrolides, telithromycin inhibits protein synthesis by acting mainly on the 50S ribosomal subunit. The defining structural characteristic is a keto function in place of the C3-cladinose moiety, which greatly improves acid stability and confers a lack of induction of MLSb resistance. Telithromycin provides potent activity against a wide spectrum of Gram-positive and Gram-negative organisms, including erythromycin-resistant pneumococci and atypical/intracellular organisms. Preliminary results from clinical trials have demonstrated that telithromycin may provide a convenient and effective compact treatment option for select respiratory tract infections such as community-acquired pneumonia, acute bacteria exacerbations of chronic bronchitis, acute sinusitis and tonsillitis/pharyngitis. (c) 2001 Prous Science. All rights reserved.
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PMID:Telithromycin (HMR 3647): The first ketolide antibiotic. 1274 33

Experimental acute sinusitis was induced in 21 New Zealand hybrid rabbits by occluding the ostium and inoculating them with Streptococcus pneumonia. While a group of rabbits with sinusitis was left untreated, two other groups were administered parenteral sodium nitroprussid (SNP) and oral levofloxacin for ten days. While staphylococci species, non-hemolytic streptococcus and contaminated flora were isolated from the sinuses of controls, Streptococcus pneumonia was re-isolated in two of six untreated rabbits, in one of six SNP administered rabbits and none of the levofloxacin treated rabbits. Serum and maxillary sinus mucosal nitric oxide (NO) levels were correlated. While the mean maxillary sinus NO level of controls was significantly higher than that of untreated rabbits, the mean maxillary sinus and serum NO levels were significantly higher in SNP administered rabbits than in the others. Although goblet cell hyperplasia and squamous cell metaplasia were detected in some slides, edema and neutrophil infiltration were the prominent findings. The most severe inflammatory changes were found in the untreated sinusitis group on the third and fifth days. The earliest improvement was observed in the levofloxacin treated rabbits. It was concluded that NO level is decreased during acute sinusitis and that SNP administration hastens the bacteriological and histological recovery.
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PMID:Serum and mucosal nitric oxide levels and efficacy of sodium nitroprussid in experimentally induced acute sinusitis. 1283 79


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