title: Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides.
abstract: OBJECTIVE
  The in vitro abilities of telithromycin, azithromycin and clarithromycin to select for resistance were compared by testing isolates of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and beta-haemolytic streptococci.
  
  
  METHODS
  Five strains each of beta-lactamase-positive and beta-lactamase-negative H. influenzae, beta-lactamase-positive and beta-lactamase-negative M. catarrhalis, S. pneumoniae, beta-haemolytic group A, group C and group G streptococci and three strains of beta-lactamase-negative ampicillin-resistant H. influenzae were evaluated. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MIC values were determined after five serial passages on antibiotic-gradient plates and after 10 serial passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of >/=4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on plates containing antibiotics at concentrations equal to the highest NCCLS breakpoints.
  
  
  RESULTS
  Azithromycin, clarithromycin and telithromycin gave a >/=4-fold increase in 20, 20 and 10 streptococcus strains, in 4, 5 and 0 H. influenzae strains and in 2, 7 and 4 M. catarrhalis strains, respectively. After 10 passages on antibiotic-free plates, 21/26 strains for azithromycin, 22/32 for clarithromycin and 1/14 for telithromycin maintained high MIC values. In single-step studies, the frequency of mutations was <10(-10) for H. influenzae and M. catarrhalis for telithromycin, azithromycin and clarithromycin. Telithromycin induced mutations at a lower rate than azithromycin and clarithromycin in streptococcal strains.
  
  
  CONCLUSIONS
  Telithromycin showed a very limited ability to select for resistance in respiratory pathogens compared with azithromycin and clarithromycin.
authors.affiliation: Laboratory of Clinical Microbiology, Department of Clinical Sciences L. Sacco Teaching Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy. microbio@unimi.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Drago
authors.forename: Elena
authors.initials: E
authors.lastname: De Vecchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Nicola
authors.forename: Alberto
authors.initials: A
authors.lastname: Colombo
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Gismondo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D005787:Gene Frequency; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D048628:Ketolides; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects*; D009154:Mutation / Q000235:genetics; D012141:Respiratory Tract Infections / Q000382:microbiology; D013291:Streptococcus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin