We first investigated this in a study using levofloxacin in CAP. The PK data was available for a total of 272 patients and 134 had an identified pathogen, demonstrating a link between exposure and response. However, we were unable to identify any linkage between levofloxacin exposure and ADRs. Since then, a randomized double-blind study has been performed investigating once versus twice daily aminoglycoside therapy and the development of nephrotoxicity. This revealed that giving a drug in a q24hr schedule caused much less nephrotoxicity than giving the same daily total dose in a q12hr schedule. Secondly, the addition of vancomycin markedly enhanced the probability of nephrotoxicity, and the probability of nephrotoxicity followed daily AUC of exposure to the agent (17).