Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0348321 (Haemophilus)
15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro activity of telithromycin, a new ketolide, was compared with beta-lactam antimicrobials against pathogens commonly associated with community-acquired respiratory tract infections. These pathogens were collected during 1999-2000 as part of the ongoing PROTEKT surveillance study. Globally, penicillin nonsusceptibility among Streptococcus pneumoniae (n = 3362) was 36.3%, ranging from 21.5% (Australasia) to 68.0% (Far East). Telithromycin showed higher potency (MIC90 0.12 mg/L) than beta-lactams against S. pneumoniae; 99.9% of all and 99.6% of multi-resistant isolates were susceptible to telithromycin. Among Streptococcus pyogenes isolates (n = 1485), 100% were susceptible to beta-lactams, and the telithromycin MIC50 and MIC90 were both 0.015 mg/L. Among Haemophilus influenzae (n = 2948), 16.6% produced beta-lactamase, which reduced the activity of ampicillin, cefaclor and cefprozil. 99.9% of H. influenzae were susceptible to telithromycin and the MIC range for M. catarrhalis was 0.004-0.5 mg/L. The first year results of PROTEKT confirmed high potency for telithromycin against common respiratory tract pathogens, including beta-lactam-resistant strains.
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PMID:Comparative in vitro activity of telithromycin and beta-lactam antimicrobials against bacterial pathogens from community-acquired respiratory tract infections: data from the first year of PROTEKT (1999-2000). 1296 61

The in vitro activity of telithromycin was compared with erythromycin A, azithromycin, clarithromycin, moxifloxacin, gemifloxacin, levofloxacin, ciprofloxacin, penicillin G, ampicillin, cefuroxime and ceftriaxone against 336 consecutive strains (83 Streptococcus pneumoniae, 168 Haemophilus influenzae and 85 Moraxella catarrhalis) isolated from patients with community-acquired respiratory tract infections. Telithromycin (MIC(90), 0.008 mg/l) was the most active drug against S. pneumoniae. Telithromycin was also highly active against M. catarrhalis (MIC(90), 0.06 mg/l), but less active against H. influenzae (MIC(90), 4 mg/l).
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PMID:In vitro activity of telithromycin compared with macrolides and fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. 1460 68

The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with GW 773546, 1.5 x 10(-9) to 6.0 x 10(-4) with GW 708408, and 7.1 x 10(-9) to 3.8 x 10(-4) with telithromycin, whereas the frequencies were 1.3 x 10(-9) to 6.0 x 10(-4) with erythromycin and azithromycin and 2.0 x 10(-9) to 2.0 x 10(-3) with clarithromycin. Alterations in the L22 protein (which were predominant) and the L4 protein were present in mutants selected by the single-step selection process. The postantibiotic effects of GW 773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides.
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PMID:Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae. 1550 29

Increasing resistance among the key pathogens responsible for community-acquired respiratory tract infections, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, has the potential to limit the effectiveness of the antibacterial agents available to treat these infections. Moreover, there are regional differences in the susceptibility patterns observed and, as treatment is usually empirical, choosing an effective treatment can be challenging. Telithromycin, the first ketolide to be approved for clinical use, offers an activity profile that covers the key respiratory pathogens including penicillin- and macrolide-resistant S. pneumoniae as well as beta-lactamase-producing H. influenzae and M. catarrhalis. In a pooled analysis of three large controlled clinical trials involving patients with acute maxillary sinusitis, the bacteriological efficacy of 5- or 10-day treatment with telithromycin and 10-day treatment with comparators was evaluated. Telithromycin administered as a once-daily 800 mg dose for 5 days achieved eradication rates of 91.8, 87.5 and 92.9% for S. pneumoniae, H. influenzae and M. catarrhalis, respectively. Bacteriological eradication of 8/10 and 12/14 isolates of S. pneumoniae resistant to penicillin and erythromycin, respectively, was also reported following 5-day treatment with telithromycin. The clinical efficacy of this regimen was equivalent to that of a 10-day regimen of telithromycin or standard 10-day courses of amoxicillin-clavulanic acid or cefuroxime axetil. Telithromycin 800mg given for 5 days was well tolerated, with the majority of adverse events being of mild or moderate intensity. These data suggest that telithromycin provides effective first-line therapy for use in patients with acute maxillary sinusitis in a short and convenient once-daily dosage regimen.
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PMID:Bacteriological efficacy of 5-day therapy with telithromycin in acute maxillary sinusitis. 1573 19

The pharmacodynamics of telithromycin, a new ketolide antibacterial, was examined in 115 patients with community-acquired pneumonia (CAP). Patients received telithromycin 800 mg qd for 7-10 days. Pharmacokinetic parameters were determined, and exposure was linked to microbiological outcome using logistic regression analysis. A breakpoint for increased probability of microbiological eradication was developed and was found to be the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) of 3.375. The final logistic regression model of microbiological outcome included body weight and AUC/MIC ratio breakpoint. This model was found in analyses of the entire population and when Streptococcus pneumoniae and Haemophilus influenzae were examined separately. The AUC/MIC ratio target attainment rate is expected to be >99.9% for S. pneumoniae and Moraxella catarrhalis and 93.1% for H. influenzae. This study demonstrated a relationship between telithromycin drug exposure and microbiological outcome. Telithromycin is expected to achieve the drug exposure breakpoint for the majority of isolates causing CAP.
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PMID:Pharmacodynamics of an 800-mg dose of telithromycin in patients with community-acquired pneumonia caused by extracellular pathogens. 1587 42

Telithromycin, a recently approved ketolide antibiotic derived from 14-membered macrolides, is active against erythromycin-resistant pneumococci. Telithromycin has enhanced activity in vitro because it binds not only to domain V of ribosomal RNA (like macrolides do) but also to domain II. However, it is not active against streptococci and staphylococci with constitutive macrolide, lincosamide, and streptogramin B resistance. Telithromycin, available in an oral formulation, is approved by the US Food and Drug Administration for use in adults for treatment of (1) community-acquired pneumonia due to Streptococcus pneumoniae (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, or Mycoplasma pneumoniae; (2) acute exacerbation of chronic bronchitis due to S. pneumoniae, H. influenzae, or M. catarrhalis; or (3) acute bacterial sinusitis due to S. pneumoniae, H. influenzae, M. catarrhalis, or methicillin- and erythromycin-susceptible Streptococcus aureus. It is not approved for treatment of tonsillitis, pharyngitis, or severe pneumococcal pneumonia. Unique visual adverse effects occurred in 0.27%-2.1% of patients receiving telithromycin therapy. Its enhanced activity against some common respiratory pathogens makes it a valuable addition to the available macrolides.
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PMID:Telithromycin: a ketolide antibiotic for treatment of respiratory tract infections. 1588 65

This study was done to evaluate the in vitro activity of a new ketolide telithromycin in comparison with clarithromycin, erythromycin, moxifloxacin and levofloxacin against Streptococcus pneumoniae (n = 67), Haemophilus influenzae (n = 139), and Moraxella catarrhalis (n = 46)collected between January and June 2003 in Hong Kong. Among the H. influenzae isolates, 25.2% produced beta-lactamase, while 97.8% of M. catarrhalis isolates produced beta-lactamase. Half of the S. pneumoniae isolates were nonsusceptible to penicillin, and 90.9% of these strains were resistant to clarithromycin and erythromycin. One (1.5%) S. pneumoniae strain was resistant to levofloxacin (MIC = 8 mg/l) and all isolates were sensitive to moxifloxacin and telithromycin with MIC <1 mg/l. H. influenzae isolates were sensitive to all fluoroquinolones tested and 2.2% of H. influenzae were resistant to clarithromycin. M. catarrhalis isolates were sensitive except 1 strain which was resistant to levofloxacin (MIC = 4 mg/l) and moxifloxacin (8 mg/l). All M. catarrhalis strains were sensitive to telithromycin with MIC90 = 0.5 mg/l. Telithromycin demonstrated high activity and no resistance was found in all these major respiratory tract pathogens.
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PMID:In vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents. 1598 Jun 28

Telithromycin is the first ketolide, which is a new class of antibacterial agents related to the macrolides that have structural modifications permitting dual binding to bacterial ribosomal RNA so that activity is retained against Streptococcus pneumoniae with macrolide-lincosamide-streptogramin(B) resistance. Clinical experience in infectious patients has shown that oral telithromycin 800mg once daily for 5-10 days is effective for the treatment of community-acquired upper and lower respiratory tract infections. Absorption of telithromycin in humans is estimated to be > or = 90%. Prior to entering the systemic circulation, telithromycin undergoes first-pass metabolism (mainly by the liver). Its absolute bioavailability is 57% and is unaffected by food. The volume of distribution of telithromycin after intravenous infusion is 2.9 L/kg. Telithromycin is 60-70% bound to serum proteins and has extensive diffusion into a range of target biological tissues, achieving concentrations above its minimum inhibitory concentration (MIC) against key respiratory pathogens throughout the dosing interval. After entering the systemic circulation, telithromycin is eliminated by multiple pathways (7% by biliary and/or intestinal excretion, 13% by renal excretion and 37% by hepatic metabolism). Telithromycin is metabolised via cytochrome P450 (CYP) 3A4 and non-CYP pathways. The identified metabolites show minimal antibacterial activity compared with the parent drug. In healthy subjects receiving telithromycin 800 mg once daily, the peak plasma concentration achieved is 2.27 microg/mL. Plasma concentrations of telithromycin show a biphasic decrease over time, with an initial disposition half-life of 2.9 hours and a terminal elimination half-life of approximately 10 hours after multiple dose administration. Steady-state plasma concentrations are achieved within 2-3 days of once-daily administration. Owing to elimination by multiple pathways there is a small increase in exposure when one of these elimination pathways is impaired, as indicated by the results of studies in special patient populations (e.g. those with hepatic or renal impairment). Dosage reductions may be recommended in patients with severe renal impairment. Inhibition of CYP3A4 by potent inhibitors such as itraconazole and ketoconazole results in a 54% and 95% increase in telithromycin area under the plasma concentration-time curve, respectively. The potential for telithromycin to inhibit the CYP3A4 pathway is similar to that of clarithromycin. The once-daily administration of telithromycin is likely to limit the potential for drug interactions and clinically significant increases in exposure. In phase III clinical trials, the telithromycin 800 mg once-daily dose has been shown to provide close to the maximum antimicrobial activity against S. pneumoniae, Haemophilus influenzae and Staphylococcus aureus in patients with community-acquired pneumonia. In conclusion, telithromycin has a well characterised and reproducible pharmacokinetic profile, with pharmacokinetic/pharmacodynamic relationships supporting an oral dosage regimen of 800 mg once daily.
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PMID:Clinical pharmacokinetics of telithromycin, the first ketolide antibacterial. 1612 80

The present study assessed the comparative in vitro killing kinetics of telithromycin, azithromycin and clarithromycin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined against Streptococcus pneumoniae, beta-haemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis strains characterized by different susceptibilities to beta-lactams and macrolides. For each bacterial species, representative strains were chosen for time-kill studies. Telithromycin showed high activity against all the tested strains with MIC ranging from < or = 0.004 to 0.5 mg/L for streptococci, from 0.008 to 8 mg/L for H. influenzae, and from 0.008 to 0.5 mg/L for M. catarrhalis. In time-kill studies, telithromycin showed an overall superior bactericidal activity in respect to macrolides, particularly against resistant strains. In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides.
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PMID:Kinetic bactericidal activity of telithromycin, azithromycin and clarithromycin against respiratory pathogens. 1630 23

Data are presented on antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptoco-ccus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis collected in Japan during years 1-3 (1999-2002) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) surveillance study. In addition to the standard panel of PROTEKT antimicrobial agents, eight other agents often used in Japan also were tested against these isolates. The majority (30%-55%) of S. pneumoniae and H. influenzae isolates were collected from patients with community-acquired pneumonia, whereas most (>70%) S. pyogenes isolates came from patients with tonsillitis/pharyngitis. Penicillin and macrolide resistance were high among isolates of S. pneumoniae, averaging 30.9%-44.5% and 77.2%-79.9%, respectively, across all centers over the 3 study years; the highest occurrences were reported among pediatric patients aged 0-2 years. The erm(B) genotype accounted for >50% of all erythromycin-resistant isolates each study year. S. pyogenes isolates were highly susceptible to most antimicrobial agents except the macrolides and tetracycline. beta-Lactamase production among H. influenzae isolates range was 8.5%-9.7% per annum. A total of 9 beta-lactamase-negative, ampicillin-resistant isolates were collected during the study. Almost all (>95%) M. catarrhalis isolates were beta-lactamase positive each year. Telithromycin was highly active against all pathogens examined in this study during all 3 years.
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PMID:Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1-3 (1999-2002). 1650 84


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