Telithromycin

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D Felmingham - One of the best experts on this subject based on the ideXlab platform.

  • activity of Telithromycin and comparators against bacterial pathogens isolated from 1 336 patients with clinically diagnosed acute sinusitis
    Annals of Clinical Microbiology and Antimicrobials, 2004
    Co-Authors: Joseph E Dohar, Rafael Canton, David J Farrell, Robert Cohen, D Felmingham
    Abstract:

    Increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections has the potential to limit the effectiveness of antibiotics available to treat these infections. Since there are regional differences in the susceptibility patterns observed and treatment is frequently empirical, the selection of antibiotic therapy may be challenging. PROTEKT, a global, longitudinal multicentre surveillance study, tracks the activity of Telithromycin and comparator antibacterial agents against key respiratory tract pathogens. In this analysis, we examine the prevalence of antibacterial resistance in 1,336 bacterial pathogens, isolated from adult and paediatric patients clinically diagnosed with acute bacterial sinusitis (ABS). In total, 58.0%, 66.1%, and 55.8% of S. pneumoniae isolates were susceptible to penicillin, cefuroxime, and clarithromycin respectively. Combined macrolide resistance and reduced susceptibility to penicillin was present in 200/640 (31.3 %) of S. pneumoniae isolates (128 isolates were resistant to penicillin [MIC >= 2 mg/L], 72 intermediate [MIC 0.12–1 mg/L]) while 99.5% and 95.5% of isolates were susceptible to Telithromycin and amoxicillin-clavulanate, respectively. In total, 88.2%, 87.5%, 99.4%, 100%, and 100% of H. influenzae isolates were susceptible to ampicillin, clarithromycin, cefuroxime, Telithromycin, and amoxicillin-clavulanate, respectively. In vitro, Telithromycin demonstrated the highest activity against M. catarrhalis (MIC50 = 0.06 mg/L, MIC90 = 0.12 mg/L). The high in vitro activity of against pathogens commonly isolated in ABS, together with a once daily dosing regimen and clinical efficacy with 5-day course of therapy, suggest that Telithromycin may play a role in the empiric treatment of ABS.

  • activity of Telithromycin against key pathogens associated with community acquired respiratory tract infections
    Journal of Infection, 2004
    Co-Authors: Donald E. Low, D Felmingham, Manickam Rangaraju, Steve D Brown, Roomi Nusrat
    Abstract:

    Abstract Objectives . To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with Telithromycin in respiratory tract infections. Methods . 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. Results . In this pooled analysis, Telithromycin mode minimum inhibitory concentration (MIC) and MIC 90 , 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 β-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. Conclusions . High levels of in vitro susceptibility to Telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

  • activities of Telithromycin against 13 874 streptococcus pneumoniae isolates collected between 1999 and 2003
    Antimicrobial Agents and Chemotherapy, 2004
    Co-Authors: David J Farrell, D Felmingham
    Abstract:

    Telithromycin MICs for 13,874 Streptococcus pneumoniae isolates collected in the first 3 years of the global PROTEKT study (1999 to 2003) were studied. There was no change in the distribution of Telithromycin MICs over this period, even in countries where Telithromycin is in use. The Telithromycin MICs for 10 isolates (0.07%) were ≥4 μg/ml, and these 10 isolates contained erm(B); there was no evidence of reproducible clonal spread between centers.

  • clinical and bacteriological efficacy of the ketolide Telithromycin against isolates of key respiratory pathogens a pooled analysis of phase iii studies
    Clinical Microbiology and Infection, 2004
    Co-Authors: Donald E. Low, S Brown, D Felmingham
    Abstract:

    ABSTRACT A pooled analysis of data from 13 phase III studies of Telithromycin in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis or group A β-haemolytic streptococcal pharyngitis and tonsillitis was undertaken. Causative key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the studies from cultures of relevant respiratory samples and tested for their susceptibility to Telithromycin, penicillin and macrolides (erythromycin A). The combined clinical and bacteriological efficacy of Telithromycin at the post-therapy, test-of-cure visit (days 17–24) was assessed in patients from whom a microbiologically evaluable pathogen was isolated at entry. More than 98% of key respiratory pathogens isolated, including penicillin G- and macrolide (erythromycin A)-resistant strains of S. pneumoniae , demonstrated full or intermediate susceptibility to Telithromycin in vitro at the breakpoints of ≤ 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of evaluating the susceptibility of isolates recovered during the clinical trials. Treatment with Telithromycin 800 mg once-daily for 5, 7 or 7–10 days resulted in high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome (88.9%), similar to the figures seen with comparator antibacterial agents. Clinical cure and eradication rates were good for all key respiratory pathogens, including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae. The results suggest that Telithromycin will provide effective empirical therapy for community-acquired upper and lower respiratory tract infections.

  • evolving resistance patterns in community acquired respiratory tract pathogens first results from the protekt global surveillance study prospective resistant organism tracking and epidemiology for the ketolide Telithromycin
    Journal of Infection, 2002
    Co-Authors: D Felmingham
    Abstract:

    In recent years, antibacterial resistance among respiratory pathogens implicated in community-acquired respiratory tract infections (RTIs) has spread worldwide at an alarming rate. Thus, there is a pressing need for new antibacterials that retain activity against resistant organisms, have a low potential to select for resistance and do not induce cross-resistance. Telithromycin is the first of a new class of antibacterials - the ketolides - that have been designed specifically to overcome resistance among respiratory tract pathogens. This paper presents the first results of the PROTEKT study (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin), a worldwide surveillance study initiated to chart the prevalence of important resistance phenotypes and genotypes and the comparative activity of Telithromycin against such strains. Analysis of over 7,000 bacterial isolates by April 2001 has confirmed the notable prevalence of strains resistant to commonly prescribed RTI antibacterials for all the pathogens studied. Telithromycin demonstrates high activity against isolates of Streptococcus pneumoniae, irrespective of penicillin G, macrolide or fluoroquinolone resistance. Telithromycin is also highly active against other respiratory tract pathogens, including Streptococcus pyogenes and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. These data justify the assertion that Telithromycin is a promising new candidate for the empirical treatment of community-acquired RTIs, particularly in the face of increasing antibacterial resistance.

David J Farrell - One of the best experts on this subject based on the ideXlab platform.

  • antibacterial activity of Telithromycin and comparators against pathogens isolated from patients with community acquired respiratory tract infections the prospective resistant organism tracking and epidemiology for the ketolide Telithromycin study year 5 2003 2004
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Francesco Blasi, David J Farrell, L Dubreuil
    Abstract:

    Abstract The activity of Telithromycin and comparator antibacterials was examined in isolates of Streptococcus pneumoniae and Haemophilus influenzae isolated from patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or sinusitis during year 5 (2003–2004) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin global resistance surveillance study. Among S. pneumoniae , penicillin nonsusceptibility and erythromycin resistance were 35.7% and 36.0%, respectively. β-Lactamase was produced by 12.3% of H. influenzae isolates. β-Lactamase–negative ampicillin-resistant strains, mainly from Japan, comprised 5.2% of global H. influenzae isolates. Telithromycin and levofloxacin were the most active agents tested against S. pneumoniae and H. influenzae (>99% of isolates susceptible) isolated from patients with CAP, AECB, or bacterial sinusitis. Amoxicillin–clavulanate, levofloxacin, and Telithromycin were the most active agents against multidrug-resistant S. pneumoniae .

  • antibacterial activity of Telithromycin and comparators against pathogens isolated from patients with community acquired respiratory tract infections the prospective resistant organism tracking and epidemiology for the ketolide Telithromycin study year 5 2003 2004
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Francesco Blasi, David J Farrell, L Dubreuil
    Abstract:

    The activity of Telithromycin and comparator antibacterials was examined in isolates of Streptococcus pneumoniae and Haemophilus influenzae isolated from patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or sinusitis during year 5 (2003-2004) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin global resistance surveillance study. Among S. pneumoniae, penicillin nonsusceptibility and erythromycin resistance were 35.7% and 36.0%, respectively. beta-Lactamase was produced by 12.3% of H. influenzae isolates. beta-Lactamase-negative ampicillin-resistant strains, mainly from Japan, comprised 5.2% of global H. influenzae isolates. Telithromycin and levofloxacin were the most active agents tested against S. pneumoniae and H. influenzae (>99% of isolates susceptible) isolated from patients with CAP, AECB, or bacterial sinusitis. Amoxicillin-clavulanate, levofloxacin, and Telithromycin were the most active agents against multidrug-resistant S. pneumoniae.

  • Telithromycin resistance in streptococcus pneumoniae is conferred by a deletion in the leader sequence of erm b that increases rrna methylation
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: Nicole Wolter, Anthony M. Smith, Keith P. Klugman, David J Farrell, John Blackman Northwood, Stephen Douthwaite
    Abstract:

    A Telithromycin-resistant clinical isolate of Streptococcus pneumoniae (strain P1501016) has been found to contain a version of erm(B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain of S. pneumoniae (PC13) with a wild-type erm(B) gene was transformed to the Telithromycin-resistant phenotype by introduction of the mutant erm(B) gene. Whereas the wild-type PC13 strain showed slight Telithromycin resistance only after induction by erythromycin (Telithromycin MIC increased from 0.06 to 0.5 μg/ml), the transformed PC13 strain is constitutively resistant (MIC of 16 μg/ml). Expression of erm(B) was quantified by real-time reverse transcription-PCR in the presence of erythromycin or Telithromycin; erm(B) expression was significantly higher in the transformed PC13 strain than the wild-type strain. Furthermore, the transformed strain had significantly higher levels of ribosomal methylation in the absence as well as in the presence of the antibiotics. Growth studies showed that the transformed PC13 strain had a shorter lag phase than the wild-type strain in the presence of erythromycin. Telithromycin resistance is conclusively shown to be conferred by the mutant erm(B) gene that is expressed at a constitutively higher level than the inducible wild-type gene. Elevated erm(B) expression results in a higher level of rRNA methylation that presumably hinders Telithromycin binding to the ribosome.

  • the effect of Telithromycin in acute exacerbations of asthma
    The New England Journal of Medicine, 2006
    Co-Authors: Sebastian L Johnston, David J Farrell, Francesco Blasi, Peter N Black, Richard J Martin, Richard B Nieman
    Abstract:

    Background We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of Telithromycin in patients with acute exacerbations of asthma. Methods A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care. The patients were randomly assigned to receive 10 days of oral treatment with Telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care. Primary efficacy end points were a change from baseline over the treatment period in symptoms (as recorded by patients in a diary card) and in the peak expiratory flow in the morning at home. The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain reaction, and culture. Results Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving Telithromycin than among those receiving placebo. Mean (±SD) scores on a test of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6 denoting severe symptoms) were 3.0±1.4 at baseline and 1.7±1.1 at the end of treatment for the Telithromycin group and 2.8±1.3 at baseline and 2.0±1.0 at the end of treatment for the placebo group. The mean decrease in symptom scores during the treatment period was 1.3 for Telithromycin and 1.0 for placebo (mean difference, −0.3; 95 percent confidence interval, −0.5 to −0.1; P = 0.004). There was no significant treatment effect on the other primary outcome measure, a change in morning peak expiratory flow. Nausea was more common among patients in the Telithromycin group than in the placebo group (P = 0.01). Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment. Conclusions This study provides evidence of the benefit of Telithromycin in patients with acute exacerbations of asthma; the mechanisms of benefit remain unclear. (ClinicalTrials. gov number, NCT00273520.)

  • Antibiotic activity of Telithromycin and comparators against bacterial pathogens isolated from 3,043 patients with acute exacerbation of chronic bronchitis
    Annals of Clinical Microbiology and Antimicrobials, 2005
    Co-Authors: Sanjay Sethi, Antonio Anzueto, David J Farrell
    Abstract:

    Background Antimicrobial therapy is considered an important component in the medical management of most patients with acute exacerbation of chronic bronchitis (AECB). The three predominant bacterial species isolated are nontypeable Haemophilus influenzae , Moraxella catarrhalis , and Streptococcus pneumoniae . Staphylococcus aureus is also frequently isolated while atypical bacteria are thought to cause up to 10% of exacerbations. Antibacterial resistance is increasing worldwide and little surveillance data exist concerning pathogens isolated from patients with AECB. Methods This study examines the prevalence of antibacterial resistance in isolates obtained from patients with clinically diagnosed AECB. A total of 3043 isolates were obtained from 85 centres in 29 countries, between 1999–2003, and were tested against the new ketolide Telithromycin and a panel of commonly used antibiotics. Results and Discussion Of the S. pneumoniae isolates, 99.9% were susceptible to Telithromycin, but only 71% were susceptible to erythromycin and 75.3% to penicillin. Of the H. influenzae isolates, 99.6% were susceptible to Telithromycin. 11.7% of these isolates produced β-lactamase. Almost 10% of S. pneumoniae were multidrug-resistant; 99.0% of these isolates were susceptible to Telithromycin. Telithromycin also demonstrated good in vitro activity against M. catarrhalis (MIC_90 = 0.12 mg/L) and was the most active compound against methicillin-susceptible S. aureus (98.9% susceptible). Conclusion Telithromycin demonstrated similar or better activity against the bacterial species investigated than the other agents, with the most complete coverage overall. These species are the predominant causative bacterial pathogens in AECB and thus the spectrum of activity of Telithromycin makes it a potential alternative for the empirical treatment of AECB.

Rodrigo B. Andrade - One of the best experts on this subject based on the ideXlab platform.

  • total synthesis of desmethyl macrolide antibiotics
    Synlett, 2015
    Co-Authors: Rodrigo B. Andrade
    Abstract:

    Macrolide antibiotics occupy a special place in the history of organic chemistry and medicine. This account chronicles the evolution of our approach that ultimately led to the successful total syntheses of four desmethyl (i.e., Me → H) analogues of Telithromycin, a semisynthetic derivative of the flagship macrolide antibiotic, erythromycin. 1 Introduction 2 Project Rationale and Retrosynthetic Analysis 3 Lessons Learned from the Total Synthesis of 4,8,10-Tridesmethyl Telithromycin 4 Total Synthesis of 4,10-Didesmethyl Telithromycin 5 Total Synthesis of 4,8-Didesmethyl Telithromycin 6 Total Synthesis of 4-Desmethyl Telithromycin 7 Biological Evaluation of Desmethyl Telithromycin Analogues 8 Concluding Remarks

  • total synthesis of desmethyl macrolide antibiotics
    Synlett, 2015
    Co-Authors: Rodrigo B. Andrade
    Abstract:

    Macrolide antibiotics occupy a special place in the history of organic chemistry and medicine. This account chronicles the evolution of our approach that ultimately led to the successful total syntheses of four desmethyl (i.e., Me → H) analogues of Telithromycin, a semisynthetic derivative of the flagship macrolide antibiotic, erythromycin. 1 Introduction 2 Project Rationale and Retrosynthetic Analysis 3 Lessons Learned from the Total Synthesis of 4,8,10-Tridesmethyl Telithromycin 4 Total Synthesis of 4,10-Didesmethyl Telithromycin 5 Total Synthesis of 4,8-Didesmethyl Telithromycin 6 Total Synthesis of 4-Desmethyl Telithromycin 7 Biological Evaluation of Desmethyl Telithromycin Analogues 8 Concluding Remarks

  • Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin
    2012
    Co-Authors: Venkata Velvadapu, Ian Glassford, Miseon Lee, Tapas Paul, Charles Debrosse, Dorota Klepacki, Meagan C. Small, Alexander D. Mackerell, Rodrigo B. Andrade
    Abstract:

    Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, and biological evaluation of 4,10-didesmethyl Telithromycin (4), a novel desmethyl analogue of the third-generation drug Telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl Telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than Telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity, suggesting that it plays an important role in antibiotic function

  • desmethyl macrolide analogues to address antibiotic resistance total synthesis and biological evaluation of 4 8 10 tridesmethyl Telithromycin
    ACS Medicinal Chemistry Letters, 2011
    Co-Authors: Tapas Paul, Dorota Klepacki, Alexander D. Mackerell, Bharat Wagh, Olgun Guvench, Rodrigo B. Andrade
    Abstract:

    There is an urgent need to discover new drugs to address the pressing problem of antibiotic-resistance. Macrolide antibiotics such as erythromycin (1) are safe, broad-spectrum antibiotics used in the clinic since 1954. Herein we report the synthesis and evaluation of 4,8,10-tridesmethyl Telithromycin (3), a novel desmethyl analogue of the 3rd-generation drug Telithromycin (2), which is a semisynthetic derivative of 1. Analogue 3 was found to possess antibiotic activity and was superior to Telithromycin (2) when tested against resistant strains of S. aureus possessing an A→T mutation at position 2058 (E. coli numbering).

Peter C Appelbaum - One of the best experts on this subject based on the ideXlab platform.

  • effect of efflux on Telithromycin and macrolide susceptibility in haemophilus influenzae
    Antimicrobial Agents and Chemotherapy, 2006
    Co-Authors: Tatiana Bogdanovich, Bulent Bozdogan, Peter C Appelbaum
    Abstract:

    This study investigated the presence of Telithromycin and azithromycin efflux in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [3H]Telithromycin and [N-methyl-3H]azithromycin in the presence and absence of carbonyl m-chlorophenylhydrazone (CCCP), a protonophore. In 17 strains for which the Telithromycin MICs were 0.06 to 0.5 μg/ml (azithromycin MICs, ≤0.06 to 0.125 μg/ml; clarithromycin MICs, ≤0.06 to 2 μg/ml), Telithromycin and azithromycin accumulations were high without CCCP and not affected by its addition, which indicates absence of efflux. In 22 strains for which the Telithromycin MICs were 0.25 to 4 μg/ml (azithromycin MICs, 0.25 to 1 μg/ml; clarithromycin MICs, 1 to 8 μg/ml), initially low levels of Telithromycin accumulation became higher after addition of CCCP, indicating a functioning efflux pump. Nineteen strains for which the Telithromycin MICs were ≥2 μg/ml had efflux as well as various mutations in ribosomal proteins L4, L22, and/or 23S rRNA (domains II and V). Of these 19 strains, the Telithromycin MICs (≥8 μg/ml) for 17 of them were significantly raised (azithromycin, MICs 4 to >32 μg/ml; clarithromycin MICs, 8 to >32 μg/ml). From these results we conclude that Telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the Telithromycin MICs were very low.

  • activities of a new fluoroketolide hmr 3787 and its des fluor derivative ru 64399 compared to those of Telithromycin erythromycin a azithromycin clarithromycin and clindamycin against macrolide susceptible or resistant streptococcus pneumoniae and s pyogenes
    Antimicrobial Agents and Chemotherapy, 2001
    Co-Authors: Kensuke Nagai, Andre Bryskier, Michael R Jacobs, Todd A Davies, Lois M Ednie, Elizabeth Palavecino, Peter C Appelbaum
    Abstract:

    Activities of HMR 3787 and RU 64399 were compared to those of three macrolides, Telithromycin, and clindamycin against 175 Streptococcus pneumoniae isolates and 121 Streptococcus pyogenes isolates. HMR3787 and Telithromycin were the most active compounds tested against pneumococci. Telithromycin and RU 64399 were equally active against macrolide-susceptible (MICs, 0.008 to 0.06 microg/ml) and -resistant S. pyogenes isolates, but HMR 3787 had lower MICs for ermB strains.

  • antipneumococcal activity of Telithromycin by agar dilution microdilution e test and disk diffusion methodologies
    Journal of Clinical Microbiology, 2000
    Co-Authors: Todd A Davies, Michael R Jacobs, Linda M Kelly, Peter C Appelbaum
    Abstract:

    Agar dilution and microdilution (both in air) and E test and disk diffusion (both in air and CO2) were used to test the activity of Telithromycin against 110 erythromycin-susceptible and 106 erythromycin-resistant pneumococci. The MICs at which 50 and 90% of strains are inhibited (MIC50s and MIC90s, respectively) for erythromycin-susceptible strains varied between 0.008 and 0.016 μg/ml and 0.016 and 0.03 μg/ml when the samples were incubated in air. By comparison, Telithromycin MIC50s and MIC90s for erythromycin-resistant strains were in air 0.03 to 0.125 and 0.125 to 0.5 μg/ml, respectively. When agar dilution was used as the reference method, essential agreement was found for 112 of 216 strains (51.9%) for microdilution, 168 of 216 (77.8%) for E test in air, and 132 of 216 (61.1%) for E test in CO2. With the exception of four strains tested by E test in CO2, all organisms were susceptible to a proposed Telithromycin susceptibility breakpoint of ≤1 μg/ml. By disk diffusion with 15-μg Telithromycin disks, all strains but one had zones of inhibition ≥19 mm in diameter when incubated in CO2, while all strains had zone diameters of ≥22 mm when incubated in air. Zone diameters in air were generally 4 to 5 mm larger than in CO2. By all methods, MICs and zones of all erythromycin-resistant strains occurred in clusters separated from those seen with erythromycin-susceptible strains. The results for macrolide-resistant strains with erm and mef resistance determinants were similar. The results show that (i) Telithromycin is very active against erythromycin-susceptible and -resistant strains irrespective of macrolide resistance mechanism; (ii) susceptibility to Telithromycin can be reliably tested by the agar, microdilution, E test, and disk diffusion methods; and (iii) incubation in CO2 led to smaller zones by disk diffusion and higher MICs by E test, but at a susceptible MIC breakpoint of ≤1 μg/ml and a susceptible zone diameter cutoff of ≥19 mm in CO2, 215 of 216 strains were found to be susceptible to Telithromycin.

  • in vitro development of resistance to Telithromycin hmr 3647 four macrolides clindamycin and pristinamycin in streptococcus pneumoniae
    Antimicrobial Agents and Chemotherapy, 2000
    Co-Authors: Todd A Davies, Michael R Jacobs, Bonifacio Dewasse, Peter C Appelbaum
    Abstract:

    The ability of 50 sequential subcultures in subinhibitory concentrations of Telithromycin (HMR 3647), azithromycin, clarithromycin, erythromycin A, roxithromycin, clindamycin, and pristinamycin to select for resistance was studied in five macrolide-susceptible and six macrolide-resistant pneumococci containing mefE or ermB. Telithromycin selected for resistance less often than the other drugs.

Roomi Nusrat - One of the best experts on this subject based on the ideXlab platform.

  • Telithromycin for the treatment of acute bacterial maxillary sinusitis a review of a new antibacterial agent
    Southern Medical Journal, 2005
    Co-Authors: Guy Tellier, Stephen A Brunton, Roomi Nusrat
    Abstract:

    Objective: Telithromycin, the first approved ketolide antibiotic, was developed to treat community-acquired respiratory tract infections, including acute bacterial maxillary sinusitis (ABMS). A previously published study showed that a 5-day course of 800 mg Telithromycin once daily is as effective as a 10-day course in the treatment of ABMS. Materials and Methods: Data were pooled from two controlled, multinational, prospective, randomized, double-blinded ABMS trials comparing 5-day Telithromycin (800 mg once daily) with 10-day amoxicillin-clavulanate (500/125 mg 3 times daily) and cefuroxime axetil (250 mg twice daily). Clinical cure and bacteriologic eradication rates were compared by means of descriptive statistics. Results: The clinical cure rate for Telithromycin was 80.9% versus 77.4% for comparators; bacteriologic eradication rate for Telithromycin was 84.9% versus 81.7% for comparators. Most adverse events were mild to moderate in intensity and, most commonly, gastrointestinal in nature. Conclusions: These results support the conclusion that 5 days of treatment with Telithromycin is as safe and effective in patients with ABMS as a 10-day course of treatment with amoxicillin-clavulanate or cefuroxime axetil.

  • pharmacodynamics of an 800 mg dose of Telithromycin in patients with community acquired pneumonia caused by extracellular pathogens
    Diagnostic Microbiology and Infectious Disease, 2005
    Co-Authors: Thomas P Lodise, Vijay O Bhargava, Andre Bryskier, Roomi Nusrat, Sandra L Preston, Sonny Chapel, Manichan Rangaraju, George L Drusano
    Abstract:

    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.

  • activity of Telithromycin against key pathogens associated with community acquired respiratory tract infections
    Journal of Infection, 2004
    Co-Authors: Donald E. Low, D Felmingham, Manickam Rangaraju, Steve D Brown, Roomi Nusrat
    Abstract:

    Abstract Objectives . To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with Telithromycin in respiratory tract infections. Methods . 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. Results . In this pooled analysis, Telithromycin mode minimum inhibitory concentration (MIC) and MIC 90 , 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 β-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. Conclusions . High levels of in vitro susceptibility to Telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

  • clinical and bacteriological efficacy and safety of 5 and 7 day regimens of Telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate community acquired pneumonia
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Guy Tellier, Roomi Nusrat, Michael S Niederman, Manish Patel, Bruce Lavin
    Abstract:

    Objectives: This study was conducted to investigate the potential equivalence in clinical efficacy and assess safety of a 5 or 7 day regimen of oral Telithromycin (800mg once daily) and a 10 day regimen of oral clarithromycin (500mg twice daily) in treating community-acquired pneumonia (CAP). Bacteriological efficacy was also compared. Methods: This was a multicentre, randomized, double-blind, active-controlled study. Patients with mild to moderate CAP received Telithromycin 800mg once a day for 5 (n 5 193) or 7 (n 5 195) days or clarithromycin 500mg twice a day for 10 days (n 5 187). In these groups, 159, 161 and 146 patients, respectively, completed the study. Results: At the post-therapy/test-of-cure evaluation, clinical cure rates (per-protocol clinical population) were 89.3% (5 days) and 88.8% (7 days) for Telithromycin, and 91.8% for clarithromycin 10 days. Satisfactory bacteriological outcome rates (per-protocol bacteriological population) were 87.7% and 80.0% for 5 and 7 days of Telithromycin, respectively, and 83.3% for 10 days of clarithromycin. Bacteriological eradication rates in the respective treatment groups were, for Streptococcus pneumoniae, 95.8% (23/24), 96.7% (29/30) and 88.5% (23/26); for Haemophilus influenzae, 88.0% (22/25), 84.0% (21/25) and 88.2% (15/17) and for Moraxella catarrhalis, 1/1, 4/5 and 3/4. Both Telithromycin regimens demonstrated clinical efficacy against pneumococcal bacteraemia (19/19), atypical pathogens (9/9) and erythromycin-resistant S. pneumoniae isolates (5/5). Most treatment-emergent adverse events were mild to moderate in intensity with most commonly reported adverse events involving the gastrointestinal system. Conclusions: Telithromycin 800mg administered once a day for 5 or 7 days was as effective and safe as clarithromycin 500mg administered twice a day for 10 days in treating patients with CAP caused by common respiratory pathogens, including macrolide-resistant isolates, and pneumococcal bacteraemia.

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