COMPARISON OF 3 DIFFERENT IN-VITRO METHODS OF DETECTING SYNERGY - TIME-KILL, CHECKERBOARD, AND E-TEST

An in vitro method of detecting synergy which is simple to perform, ac curate, and reproducible and has the potential for clinical extrapolat ion is desirable. Time-kill and checkerboard methods are the most wide ly used techniques to assess synergy but are time-consuming and labor- intensive. The Epsilometer test (E test), a less technically demanding test, has not been well studied for synergy testing, We performed syn ergy testing of Escherichia coli ATCC 35218, Enterobacter cloacae ATCC 23355, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus A TCC 29213 with various combinations of cefepime or ceftazidime with to bramycin or ciprofloxacin using time-kill, checkerboard, and E test te chniques. Time-kill testing was performed against each organism alone and in combinations at one-fourth times the MIC (1/4x MIG) and 2x MIG. With checkerboard tests, the same combinations were studied at concen trations ranging from 1/32x to 4x MIG. Standard definitions for synerg y, indifference, and antagonism were utilized. E test strips were cros sed at a 90 degrees angle so that the scales met at the MIC of each dr ug alone, and the fractional inhibitory concentration index was calcul ated on the basis of the resultant zone of inhibition, All antimicrobi al combinations demonstrated some degree of synergy against the test o rganisms, and antagonism was infrequent, Agreement with time-kill test ing ranged from 44 to 88% and 63 to 75% by the checkerboard and E test synergy methods, respectively, Despite each of these methods utilizin g different conditions and endpoints, there was frequent agreement amo ng the methods, Further comparisons of the E test synergy technique wi th the checkerboard and time-kill methods are warranted.