Antimicrobial activity and spectrum of SCH27899 (Ziracin (R)) tested against Gram-positive species including recommendations for routine susceptibility testing methods and quality control

SCH27899 is an oligosaccharide, everninomicin antibiotic with activity prim arily against Gram-positive pathogens. The activity of SCH27899 was evaluat ed against 360 routine clinical isolates by the broth microdilution (BMD), agar dilution (ADI, disk diffusion (DD), and Etest (AB BIODISK, Solna, Swed en) methods. In addition, results from a nine center SCH27899 quality contr ol (QC) trial were used to establish QC ranges. SCH27899 MICs for 330 Gram- Positive strains, including multiply-resistant staphylococci and enterococc i, ranged from 0.015 to 1 mu g/ml with MIC(90)s of 0.12 to 0.5 mu g/ml. SCH 27899 had no measurable activity against the 30 selected Gram-negative stra ins tested (MICs, > 256 mu g/ml), with the exception of Moraxella catarrhal is MICs, 0.12 mu g/ml). Etest MICs for SCH27899 correlated well with AD and BA ID results with > 90% of MICs within +/- one log, dilutions of the refe rence rest results. Three disk concentrations (2.5-, 5-, 10-mu g) of SCH278 99 were evaluated, but minimal difference of zone diameters between disk dr ug contents was observed (+/- 2 mm). SCH27899-disk zone diameters correlate d poorly with reference MICs due-to small zone diameters (range, 11 to 22 m m) attributed to poor diffusion through agar-mediums, a product of this com pound's high molecular weight and solubility. The use of the DD method for SCH27899 was not recommended. The proposed MIC quality assurance limits for SCH27899 using Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 was 0.06 to 0.25 mu g/ml for both QC strains and methods. SCH278 99 appears to be a eveminomicin-derivative widely active against important Gram-positive cocci, and in vitro dilution testing methods would be preferr ed for clinical use, validated by the recommended MIC control ranges cited in this report. (C) 1999 Elsevier Science Inc.