Antipneumococcal activity of telithromycin by agar dilution, microdilution, E test, and disk diffusion methodologies

Agar dilution and microdilution (both in air) and E test and disk diffusion (both in air and CO2) 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(50)s, respectively) for erythromycin-susceptible strains varied between 0.008 and 0.016 mu g/ml and 0.016 and 0.03 mu g/ml when the samples were incubated in air. By comparison, telithromycin MIC(50)s and MIC(50)s for erythromycin-resistant strains were in air 0.03 to 0.125 and 0.125 to 0.5 mu g/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 CO2. With the exception of four strains tested by E test in CO2, all organisms were susceptible to a proposed telithromycin susceptibility breakpoint of less than or equal to 1 mu g/ml. By disk diffusion with 15-mu g telithromycin disks, all strains but one had zones of inhibition greater than or equal to 19 mm in diameter when incubated in CO2, while all strains had zone diameters of greater than or equal to 22 mm when incubated in air. Zone diameters in air were generally 4 to 5 mm larger than in CO2. 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 erythromgrcin-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, led to smaller zones by disk diffusion and higher MICs by E test, but at a susceptible MIC breakpoint of less than or equal to 1 mu g/ml and a susceptible zone diameter cutoff of greater than or equal to 19 mm in CO2, 215 of 216 strains were found to be susceptible to telithromycin.