The influence of acute kidney injury on antimicrobial dosing in critically ill patients: are dose reductions always necessary?

Optimal dosing of antimicrobial therapy is pivotal to increase the likelihood of survival in critically ill patients with sepsis. Drug exposure that maximizes bacterial killing, minimizes the development of antimicrobial resistance, and avoids concentration-related toxicities should be considered the target of therapy. However, antimicrobial dosing is problematic as pathophysiological factors inherent to sepsis that alter may result in reduced concentrations. Alternatively, sepsis may evolve to multiple-organ dysfunction including acute kidney injury (AKI). In this case, decreased clearance of renally cleared drugs is possible, which may lead to increased concentrations that may cause drug toxicities. Consequently, when dosing antibiotics in septic patients with AKI, one should consider factors that may lead to underdosing and overdosing. Drug-specific pharmacokinetic and pharmacodynamic data may be helpful to guide dosing in these circumstances. Yet, because of the high interpatient variability in pharmacokinetics of antibiotics during sepsis, this issue remains a significant challenge.