title: Antimicrobial activity of SCH27899 (Ziracin), a novel everninomicin derivative, tested against Streptococcus spp.: disk diffusion/etest method evaluations and quality control guidelines. The Quality Control Study Group.
abstract: To combat the increasing rates of penicillin resistance among pneumococci and viridans group streptococci, new Gram-positive active agents are needed to 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 MICs among the penicillin-susceptible and -resistant streptococci tested ranged from < or = 0.008-0.5 microgram/mL. Organism groups with their respective MIC90s were as follows: Streptococcus pneumoniae (100 strains) and beta-haemolytic streptococci (70 strains), 0.12 microgram/mL; Streptococcus bovis (10 strains), 0.25 microgram/mL; and viridans group streptococci (124 strains), 0.5 microgram/mL. Etest SCH27899 MICs correlated well with broth microdilution MICs (92% +/- one log2 dilution, 98% +/- two log2 dilutions). Agar dilution SCH27899 MICs correlated well with broth microdilution MICs, but a shift toward slightly higher agar dilution MICs was attributed to difficulties in reading trailing endpoints with this method. Three concentrations (2.5, 5, and 10 micrograms) of SCH27899 were used for the disk diffusion method with small inhibition zone diameters (range, 11 to 19 mm) and limited variation 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 nine-center (30 tests per center) quality-control trial are < or = 0.016 to 0.032 microgram/mL for Etest, and 0.008 to 0.032 microgram/mL for broth microdilution tests from an earlier study. Because of the limited diffusion ability and bacteriostatic nature of SCH27899, MICs should be read at 80% of inhibition with agar in vitro systems (Etest, agar dilution), and the disk diffusion method is not recommended.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Marshall
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: M E
authors.initials: ME
authors.lastname: Erwin
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D017408:Guidelines as Topic; D006801:Humans; D008826:Microbial Sensitivity Tests; D011786:Quality Control; D013291:Streptococcus / Q000187:drug effects*