DEVELOPMENT OF INTERPRETIVE CRITERIA AND QUALITY-CONTROL LIMITS FOR MACROLIDE AND CLINDAMYCIN SUSCEPTIBILITY TESTING OF STREPTOCOCCUS-PNEUMONIAE

A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for ant imicrobial susceptibility testing of Streptococcus pneumoniae with azi thromycin, clarithromycin, dirithromycin, and clindamycin. The MICs of all of the agents plus erythromycin for 302 clinical isolates of pneu mococci that had been selected with an emphasis on resistant strains w ere determined by use of the National Committee for Clinical Laborator y Standards (NCCLS)-recommended broth microdilution procedure, The zon e diameters of the isolates were also determined for the same agents e xcept erythromycin by the NCCLS disk diffusion test procedure, Repeate d testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of MIC and zone diameter qualit y control ranges for these agents, Interpretive criteria for the MIC o f azithromycin were established and were as follows: susceptible, less than or equal to 0.5 mu g/ml; intermediate, 1 mu g/ml; and resistant, greater than or equal to 2 mu g/ml. The interpretive criteria advocat ed for the MICs of clarithromycin and clindamycin were as follows: sus ceptible, less than or equal to 0.25 mu g/ml; intermediate, 0.5 mu g/m l; and resistant, greater than or equal to 1 mu g/ml. Comparison of MI Cs and disk diffusion zone diameters led to the development of interpr etive criteria for the zone diameters for azithromycin, clarithromycin , and clindamycin that correlated well with these MIC breakpoints. Tes ting of this organism collection also led to the reestablishment of th e erythromycin MIC breakpoints as being identical to those of clarithr omycin, which resulted in equivalent cross-susceptibility and cross-re sistance for the three macrolides that are currently marketed in the U nited States, Thus, the susceptibility of pneumococci to azithromycin and clarithromycin can be predicted accurately by testing only erythro mycin in clinical laboratories, This recommendation, as well as the in terpretive and quality control criteria that are described, have been accepted by NCCLS and are included in the latest NCCLS susceptibility testing guidelines.