title: [Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections].
abstract: 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.
authors.affiliation: Centro de Estudios en Antimicrobianos, San Isidro, Buenos Aires, Argentina. casellasjm@cpsarg.com
authors.forename: J M
authors.initials: JM
authors.lastname: Casellas
authors.forename: M
authors.initials: M
authors.lastname: Visser
authors.forename: N
authors.initials: N
authors.lastname: Mac Dougall
authors.forename: B
authors.initials: B
authors.lastname: Coco
authors.forename: G
authors.initials: G
authors.lastname: Tomé
authors.forename: L
authors.initials: L
authors.lastname: Gliosca
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000188:drug therapy; D004352:Drug Resistance, Microbial; D006801:Humans; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D013020:South America
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C106791:telithromycin