Subtraction serum bactericidal assay: a method for estimating in vivo effects of antibiotic combinations.

The subtraction serum bactericidal assay has been developed to assess the effects of the individual components of antibiotic combinations in serum specimens from patients with serious bacterial infection. The technique can be performed easily with conventional microtiter technology, and the results compare favorably with those obtained by conventional in vitro determinations of the additive and synergistic activity of fixed antibiotic combinations against various Enterobacteriaceae. Three combinations of gentamicin and ampicillin were used, and synergistic or additive activity was demonstrated against each of the 11 clinical isolates tested, but only with one or two of the antibiotic combinations. This finding suggests the clinical importance of a test that can determine the effects of the actual concentrations of individual antibiotics that are achieved in patients with serious infections that are being treated with antibiotic combinations.