Antimicrobial activity of SCH27899 (Ziracin (R)), a novel everninomicin derivative, tested against Streptococcus spp.: Disk diffusion/etest method evaluations and quality control guidelines

To combat the increasing rates of penicillin resistance among pneumococci a nd viridans group streptococci, new Grampositive active agents are needed t o avoid the overuse of vancomycin. SCH27899 is an everninomicin derivative with strong activity against glycopeptide-resistant enterococci, oxacillin- resistant staphylococci, and penicillin-resistant streptococci. This study tests the in vitro activity of SCH27899 against 304 strains of streptococci and evaluates the quality of the agar dilution, broth microdilution, disk diffusion, and Etest methods for this antimicrobial agent. Quality-control (QC) ranges for SCH27899 are also proposed. SCH27899 broth microdilution MI Cs among the penicillin-susceptible and -resistant streptococci tested rang ed from less than or equal to 0.008-0.5 mu g/mL. Organism groups With their respective MIC(90)s were as follows: Streptococcus pneumoniae (100 strains ) and beta-haemolytic streptococci (70 strains), 0.12 mu g/mL; Streptococcu s bovis (10 strains), 0.25 mu g/mL; and viridans group streptococci (124 st rains), 0.5 mu g/mL. Etest SCH27899 MICs correlated well with broth microdi lution MICs (92% +/- one log(2) dilution, 98% +/- two log(2) dilutions). Ag ar dilution SCH27899 MICs correlated well with broth microdilution MICs, bu t a shift toward slightly higher agar dilution MICs was attributed to diffi culties in reading trading endpoints with this method. Three concentrations (2.5, 5, and 10 mu g) of SCH27899 were used for the disk diffusion method w ith small inhibition zone diameters (range, 11 to 19 mm) and limited variat ion between diameters (+/-2 mm) as a result, both products of this compound 's high molecular weight and poor diffusion through agar mediums. Proposed control ranges for SCH27899 when testing S. pneumoniae ATCC 49619 from a ni ne-center (30 tests per center) quality-control trial are less than or equa l to 0.016 to 0.032 mu g/mL for Etest, and 0.008 to 0.032 mu g/mL for broth microdilution tests from an earlier study. Because of the limited diffusio n ability and bacteriostatic nature of SC27899, MICs should be read at 80% of inhibition with agar in vitro systems (Etest, agar dilution), and the di sk diffusion method is not recommended. (C) 1999 Elsevier Science Inc.