Effects of storage temperature and pH on the stability of eleven β-lactam antibiotics in MIC trays

Abstract

Microdilution MIC test trays containing 11 beta-lactam antibiotics in Mueller-Hinton broth at pH 7.31 or 6.80 were prepared and stored at 4, -10, -25, and -70°C. The drugs tested were ampicillin, ticarcillin, mezlocillin, piperacillin, azlocillin, cefazolin, cefotaxime, moxalactam, cefoperazone, ceftriaxone, and imipenem. MICs for Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were determined at weekly intervals for up to 1 year. The data from the MIC determinations showed the stability of antimicrobial activity over time to be -70°C > -25°C ~ 4°C >> -10°C. The relative stability at 4° C as compared with that at -10°C cannot be explained by desiccation, as determined by changes in broth sodium concentrations. The relative instability at -10°C may have been caused in part by a temperature fluctuation, resulting in intermittent freezing and thawing of the antibiotics. Some of the drugs appeared to be more stable when diluted in broth at pH 6.80, but endpoints were more difficult to read. Cefazolin and cefoperazone were stable at all four storage temperatures. Cefotaxime, moxalactam, and ceftriaxone also were relatively stable. The other drugs showed moderately rapid to rapid deterioration at each temperature except -70°C. Storage at -25°C is suitable for up to 3 months for many, but not all, beta-lactams; -10°C appears to be unsuitable. Storage at -70°C is recommended.