Evaluation of telithromycin against Streptococcus pneumoniae with ribosomal mutations utilizing in vitro time–kill methodology

Dandekar, Prachi K.; Tessier, Pamela R.; Farrell, David J.; Nightingale, Charles H.; Nicolau, David P.

doi:10.1016/j.ijantimicag.2005.07.013

Cited by 1 publication

(1 citation statement)

References 9 publications

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“…Strains with mutations in L22 may have MICs of 1 mg/L. 51 Ketolides also show good activity against clinical S. pyogenes isolates including erythromycin A-resistant strains harbouring the erm(A) or mef(A) (efflux) genotype. Some, but not all, erm(B)-positive S. pyogenes strains may be telithromycin-resistant with MICs of up to 64 mg/L.…”

Section: Reviewmentioning

confidence: 99%

Clinical efficacy of ketolides in the treatment of respiratory tract infections

Reinert

2004

Journal of Antimicrobial Chemotherapy

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Ketolides are a new class of semi-synthetic agents derived from erythromycin A designed to overcome erythromycin A resistance in Streptococcus pneumoniae. Telithromycin (HMR 3647) is the first member of this new class to be approved for clinical use. Cethromycin (ABT-773) has been developed up to Phase III, but its further development seems questionable at the moment. Other ketolides are only in the first stages of preclinical development and may not be available within the foreseeable future. Ketolide compounds inhibit bacterial protein synthesis by interacting with the peptidyl transferase site of the 50S ribosomal subunit, and interact closely with domains II at A752 and V at A2058 and A2059 of the 23S rRNA. These compounds also inhibit the formation of the 50S subunit of the ribosome. Ketolides show good activity against the Gram-positive bacteria responsible for respiratory tract infections including penicillin G- and erythromycin A-resistant S. pneumoniae. The 15 clinical trials with telithromycin published to date include four randomized, double-blind comparative trials and three open-label studies in community-acquired pneumonia, three randomized double-blind trials in acute exacerbation of chronic bronchitis, two randomized double-blind trials in pharyngitis, and two double-blind comparative trials and one open-label trial in acute maxillary sinusitis. Clinical response rates were favourable in all clinical trials, with eradication rates in patients with pneumococcal bacteraemia and penicillin G- and erythromycin A-resistant pneumococcal infections at least as high as those of comparators. As resistance to macrolides continues to emerge, the availability of other ketolides besides telithromycin and a development programme for the application of ketolides in children would appear to be warranted to obtain a new class of antibiotics that may one day replace macrolides.

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Section: Reviewmentioning

confidence: 99%

Clinical efficacy of ketolides in the treatment of respiratory tract infections

Reinert

2004

Journal of Antimicrobial Chemotherapy

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Evaluation of telithromycin against Streptococcus pneumoniae with ribosomal mutations utilizing in vitro time–kill methodology

Cited by 1 publication

References 9 publications

Clinical efficacy of ketolides in the treatment of respiratory tract infections

Clinical efficacy of ketolides in the treatment of respiratory tract infections

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