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54 Firsov et al.84I E ABBC AAC AUBC–11084+–210Viable counts , log CFU/ml84084084+++–58116233AUC/MI C,h084+46600 10 20 30 40 50 0 10 20 30 40 50 0 10 20 30 40 50 0 10 20 30 40 50τ τ τ τTime, hFIGURE 8 Time-kill curves of Staphylococcus aureus exposed to gemifloxacin and areasexploited by I E , ABBC, AAC, and AUBC) ( ) including the zones of vanished effect ( ) andexcluding the zones of persisting effect ( ). Source: From Ref. 65.Sensitivity of the End Points to Changes in the AUC/MIC RatioAll four indices of initial killing are narrowly sensitive to changes in the AUC/MICratio. For example, in the above study with ciprofloxacin-exposed E. coli (51), 1000-fold differences in the AUC/MIC ratio induced only twofold differences in T 90% ,T 99% , T 99.9% , and k elb in contrast to a sixfold difference in D log N min as an index of“intermediate” killing. In the same study, a point index of the entire antimicrobialeffect, D log N t (t ¼ 12 hours), was even more sensitive to AUC/MIC increases: a10-fold range of D log N t corresponded to a 450-fold range of AUC/MIC ratios.As a rule, integral indices of the entire effect are more sensitive to changes inthe AUC/MIC ratio than indices of initial killing. Similar eightfold changes inthree t-dependent integral indices, AUBC, AAC, and ABBC, were reported with a450-fold range of ciprofloxacin AUC/MICs against E. coli (51). Much greatersensitivity to the simulated AUC/MIC ratio was observed in the same study forT E and I E (20- and 30-fold changes, respectively).Interrelations of Different End Points and Their Abilities to Predict theEntire Antimicrobial EffectBeing less precise, most point indices (T 90% , T 99% , T 99.9% , t min , D log N min ,andD logN t ) except for T E often conflict with each other making evaluation of the antimicrobial