Development of a meropenem susceptibility disc: drug content, preliminary interpretive and quality control criteria and potency bioassay

Abstract

Laboratory studies were conducted to develop an appropriate susceptibility disc for meropenem. Laboratory-prepared paper discs containing 5, 10, and 20 micrograms of meropenem were investigated. Agar dilution MICs and agar disc diffusion tests were performed with 367 rapidly growing clinical isolates by methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Agar disc diffusion tests with 10 micrograms meropenem discs acceptably defined organisms as susceptible or resistant. The preliminary interpretive zone size criteria for 10 micrograms meropenem discs were: susceptible, greater than or equal to 14 mm, and resistant, less than or equal to 10 mm, by application of the NCCLS imipenem MIC interpretive susceptible and resistant breakpoints to the meropenem data. A total of 270 agar disc diffusion assays were performed with each of four ATCC reference strains, using prototype discs (Becton Dickinson (BBL] containing 10 micrograms meropenem. The preliminary quality control limits for agar disc diffusion tests with these discs are: Escherichia coli ATCC 25922, 28-32 mm; Pseudomonas aeruginosa ATCC 27853, 26-31 mm; Staphylococcus aureus ATCC 25923, 33-39 mm; and Enterococcus faecalis ATCC 29212, 19-23 mm. Further studies are necessary to re-evaluate both the preliminary interpretive and quality control criteria before definitive limits can be established. A reproducible, large plate bioassay with Enterococcus faecalis ATCC 29212 was developed to monitor meropenem disc potency.