An Enzymatic Assay for Monitoring Serum, Cerebrospinal Fluid, and Urine Concentration of β-Lactam Antibiotics

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Abstract
An enzymatic assay for the determination of the concentrations of various .beta.-lactam antibiotics in serum urine, and cerebrospinal fluid samples is described. Recently developed .beta.-lactam derivatives are used as competitive inhibitors of the breakdown of the labile colored .beta.-lactam compound PADAC, which serves as the substrate for the various .beta.-lactamases. Under the conditions of the assay, there is effectively no interference due to the matrix. The assay is not influenced by other antibiotics such as aminoglycosides, macrolides, ansamycines, tetracyclines, fusidic acid or fosfomycin. The C.V [coefficient cf variability] for within-run precision ranged from 3.7-4.4%, depending on the .beta.-lactam derivative. The sensitivity of the assay is at least comparable with that of conventional procedures. Excellent correlations were observed between the enzymatic and the microbiological procedures; correlation coefficients: r = 0.988 for 22 imipenem samples, r = 0.968 for 16 cefotaxime samples, and r = 0.989 for 16 piperacillin samples routinely sent to the laboratory.