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[78-80] These problems could be avoided by using a separate line wherever possible or by using a prolonged infusion strategy. Consideration should be given to the accumulation of these drugs when administering them to patients with renal dysfunction because these drugs are eliminated through the kidneys. As discussed below, concentration monitoring could prove useful in achieving a balance between drug accumulation and target drug concentrations. ��-Lactams are generally considered to have a higher safety window with relatively few adverse effects. Case series and retrospective reviews of ��-lactam-associated adverse effects have been reported.[81-83] However, there are no prospective clinical studies evaluating the toxicity of ��-lactams as a primary end-point. Neurotoxicity is the most reported serious adverse effect of ��-lactams.[84, Moroxydine 85] Benzylpenicillin, cefepime, ceftazidime and imipenem are considered to be the high-risk ��-lactams for neurotoxicity.[86] Renal impairment, excess doses and/or concentrations, age and a prior history of neurological disorders are known to be predisposing factors.[82, 83] Neurotoxicity due to ��-lactams may be underdiagnosed owing to the concomitant factors associated with these manifestations in critically ill patients; therefore, clinicians should be aware of the predisposing factors for ��-lactam-associated neurotoxicity. Concentration monitoring in high-risk patients this website could be a potentially useful tool to avoid such effects, although adverse effects are considered rare. Pharmacokinetic variations in critically ill patients due to physiological changes have been well described elsewhere.[15] In general, an increase in V d and an increase or decrease in drug clearance is common in critically selleck chemicals ill patients. In addition, such changes are largely unpredictable, with a great inter- and intrapatient variability over time.[73, 87, 88] This unpredictability significantly increases the potential for suboptimal concentrations and provides difficult challenges for clinicians in choosing doses that will optimize the dosing to achieve the targets. Therefore, because clinicians do not know what concentrations are being achieved by their dosing strategies, concentration monitoring of ��-lactam antibiotics in critically ill patients could be considered highly valuable. Indeed, the role of therapeutic drug monitoring (TDM) of antimicrobials has been reviewed recently.[89] Therapeutic drug monitoring has been instituted for aminoglycosides and glycopeptides to reduce the rate of toxicity. However, because of the safety profile of ��-lactams, TDM was thought unnecessary for these drugs until recently. In line with PK changes in critically ill patients, a few studies have reported insufficient PD target attainment with ��-lactams in these patients.