title: Antipneumococcal activity of telithromycin by agar dilution, microdilution, E test, and disk diffusion methodologies.
abstract: Agar dilution and microdilution (both in air) and E test and disk diffusion (both in air and CO(2)) 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 (MIC(50)s and MIC(90)s, respectively) for erythromycin-susceptible strains varied between 0.008 and 0.016 microg/ml and 0.016 and 0.03 microg/ml when the samples were incubated in air. By comparison, telithromycin MIC(50)s and MIC(90)s for erythromycin-resistant strains were in air 0.03 to 0.125 and 0. 125 to 0.5 microg/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 CO(2). With the exception of four strains tested by E test in CO(2), all organisms were susceptible to a proposed telithromycin susceptibility breakpoint of < or =1 microg/ml. By disk diffusion with 15-microg telithromycin disks, all strains but one had zones of inhibition > or =19 mm in diameter when incubated in CO(2), while all strains had zone diameters of > or = 22 mm when incubated in air. Zone diameters in air were generally 4 to 5 mm larger than in CO(2). 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 CO(2) led to smaller zones by disk diffusion and higher MICs by E test, but at a susceptible MIC breakpoint of < or =1 microg/ml and a susceptible zone diameter cutoff of > or =19 mm in CO(2), 215 of 216 strains were found to be susceptible to telithromycin.
authors.affiliation: Department of Pathology, Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Davies
authors.forename: L M
authors.initials: LM
authors.lastname: Kelly
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: P C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests / Q000379:methods*; D011008:Pneumococcal Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; C106791:telithromycin