Importance of high creatinine clearance for antibacterial treatment in sepsis

Despite significant advances in organ support systems, and an improved understanding of the cellular and humoral mechanisms driving sepsis, there is still an unacceptably high in-hospital mortality rate associated with this syndrome. A key component to improving outcomes is the application of early antibacterial therapy, in sufficient dose and spectrum. This relies on an understanding of the relevant pharmacological properties of the chosen agent, in addition to the alterations in drug handling that are unique to the critically ill. In particular, the host response, in addition to the application of resuscitation fluids and vasoactive agents, can significantly alter renal drug elimination in this setting. A phenomenon termed augmented renal clearance, or ARC, is being increasingly recognised in subsets of critically ill patients. While plasma creatinine concentrations and other formulae estimating glomerular filtration lack sensitivity in identifying ARC, a measured creatinine clearance is a feasible and easily repeatable measure that can assist the clinician in identifying those at risk of sub-optimal drug exposure. Importantly, this should be routinely considered by the prescriber, in order to improve the chances of therapeutic success and reduce the opportunity for the selection of drug-resistant strains.