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452 Forrest and Drusanosignificant. Of the other covariates evaluated, only concurrent use of vancomycinaffected the time-to-event in a Cox proportional hazards model. This is displayedin Figure 2.Consequently, when one takes both analyses into account, the vast bulk ofaminoglycoside nephrotoxicity can be avoided by simply dosing intermittently(once-daily, or less frequently, depending on baseline renal function), stoppingtherapy in the “protected window” provided by once-daily dosing (stopping after5–7 days) and avoiding concurrent vancomycin administration.Avoiding toxicity is critical, but is only one half of optimizing drug therapy.In addition, we must provide adequate antimicrobial therapy. Kashuba et al. (8)examined the relationship between aminoglycoside AUC/minimum inhibitoryconcentration (MIC) ratio and the likelihood of fever resolution. This is displayedin Figure 3.If one takes the day 7 relationship (still in the “protected widow”), an AUC/MIC of 156 will provide approximately a 90% probability of fever resolution. Foran MIC of 0.5 mg/L, an AUC of 78 is required to hit the target and will generate aprobability of nephrotoxicity of