Telithromycin was the first ketolide to be approved in Europe and is in the approval process in the United States. It is structurally related to the
macrolides; it has a keto group in the C3 position rather than
cladinose. A
carbamate group is also present at C11-C12. As a result, it has a reduced induction of the MLSB resistance mechanism (erm gene), it is not affected by the flux mechanism (mef gene), it has higher stability at low pH and has increased intrinsic activity compared with
clarithromycin and
azithromycin. Phase III studies have shown
telithromycin to be effective in the treatment of community-acquired upper and lower
respiratory tract infections. Its long half-life allows for oral once-daily dosing. From a pharmacokinetic point of view, its activity has been shown to be AUC(24h)/MIC dependent. It is active against bacteria involved in atypical
pneumonia. The aim of our study was to determine the activity of
telithromycin in isolates with defined resistance phenotypes obtained from community-acquired
respiratory tract infections. Twelve centers in Argentina, Chile, Paraguay and Uruguay participated in the study. Each center collected three strains of the following species and resistance patterns: S. pyogenes, S. pneumoniae with resistance or intermediate resistance to
oxacillin,
erythromycin-resistant S. pneumoniae,
clindamycin-resistant S. pneumoniae,
oxacillin-susceptible S. aureus,
erythromycin-resistant S. aureus,
ampicillin-susceptible and -resistant M. catarrhalis and H. influenzae.
Agar diffusion susceptibility tests with NeoSensitabs
tablets (Rosco, Denmark) were carried out at each center. Isolates were sent to the coordinating center, where MICs were determined using
agar microdilution and the Seppala test was used to determine the resistance mechanism to
macrolides. The 327 isolates received were susceptible to
telithromycin. Eighty percent of the
erythromycin-resistant S. pneumoniae isolates were likely resistant due to a flux mechanism, and all those resistant to
clindamycin were resistant due to the erm inducible mechanism. Only 20 out of 36 strains of
clindamycin-resistant S. pneumoniae and 25 of the 36
ampicillin-resistant H. influenzae strains could be collected, thereby showing that these resistance patterns are less common in the participating South American countries than in other areas. The in vitro activity of
telithromycin suggests that it is a promising antibacterial
drug for the treatment of community-acquired
respiratory tract infections.