Interpretation of susceptibility testing of ceftriaxone

Susceptibility of a variety of bacterial isolates to ceftriaxone was determined by Kirby-Bauer assays using 30 micrograms ceftriaxone disks and by microdilution (MIC) assays using standard procedures. The relation between zones of inhibition and MICs was expressed by the following regression equation: zone diameter = 22.98-2.653 In (MIC). Using this regression line and the breakpoints estimated from ceftriaxone concentrations in plasma 12 to 24 hours after 1- and 2-g doses, the susceptibility of a pathogen to ceftriaxone was classified as follows: susceptible-zone 16 mm or greater, MIC 16 micrograms/ml or less; moderately susceptible-zone 13 to 15 mm, MIC 17 to 63 micrograms/ml; resistant-zone 12 mm or less, MIC 64 micrograms/ml or greater. These breakpoints were used to determine the susceptibility of organisms isolated during clinical studies in the United States. The correlation between the in vitro results and the bacteriologic outcomes achieved in the clinical cases was analyzed to assess the suitability of the chosen breakpoints. The results of the disk assays were correctly predictive of bacteriologic responses with 1,388 of 1,513 organisms (91.7 percent), whereas the results of dilution assays correctly predicted the response with 897 of 941 organisms (95.3 percent). The correlation between in vitro results and bacteriologic outcome in patients treated with ceftriaxone was equivalent or superior to that achieved in patients treated with the comparative agents cefamandole and cefazolin. Thus, the chosen cutoff points for indicating susceptibility and resistance to ceftriaxone appear to be suitable and highly predictive of clinical success.