COMPARATIVE IN-VITRO PHARMACODYNAMICS OF IMIPENEM AND MEROPENEM AGAINST PSEUDOMONAS-AERUGINOSA

MICs are commonly used to assess the in vitro activities of antimicrob ial agents; however, they provide minimal information on the pattern o f bacterial activities, Time-kill studies with extensive sampling allo w assessment of both the rate and extent of bacterial killing and regr owth, We compared imipenem and meropenem by both MIC-MBC testing and a time-kill study with P, aeruginosa 27853. In the time-kill study, con centration/MIC ratios ranging from 0.0625 to 32 times the MIC were stu died, The kill rate, time to 99.9% kill, doubling time of regrowth, an d area under the bacterial killing curve (AUKC) were evaluated, Degrad ation during the testing procedure was accounted for by assessing actu al drug exposure as determined by the area under the concentration-tim e curve, Pharmacodynamic parameters were compared by using the Wilcoxo n signed rank test, The modal MIC and MBC for imipenem were 2 and 4 mu g/ml, respectively, and those for meropenem were 0.25 and 0.5 mu g/ml , respectively, In the time-kill study, both agents displayed concentr ation-dependent activity over a range of 0.25 to 4 times the MIG. Init ial killing (0 to 1 h) was faster with imipenem at the same concentrat ion/MIC ratios (P = 0.0506), The time to 99.9% kill was approximately 5 h for both agents, When regrowth occurred, the doubling rate for imi penem, which was the same as that for the growth control, was twice as rapid as that for meropenem, At the same concentrations, the AUKCs ov er 24 h were lower for meropenem than for imipenem (P = 0.0280); howev er, when normalized by MIG, imipenem resulted in smaller AUKCs, Compar ison of plots of area under the concentration-time curve versus AUKC, which accounted for drug degradation and actual drug exposure, reveale d that meropenem was three times more active than imipenem, rather tha n the eightfold difference suggested by MICs. Time-kill curves with ex tensive sampling and measurement of actual drug exposure, rather than traditional MIC testing, may more accurately assess differences in the in vitro activities of antimicrobial agents.