Impact of Loading Doses on the Time to Adequate Predicted Beta-Lactam Concentrations in Prolonged and Continuous Infusion Dosing Schemes

TO THE EDITOR—We applaud the work by Roberts et al that was recently published in the Journal [1].As shown in this work and others, achievement of pharmacokinetic– pharmacodynamic (PK/PD) targets for beta-lactam antibiotics has been correlated with improved mortality among the critically ill [1, 2]. Similarly, hastening time to effective antimicrobial therapy in the setting of septic shock has been shown to improve the probability of survival [3–5]. For beta-lactams, maintenance of free ( f ) drug concentrations above an organism’s minimum inhibitory concentration (MIC) for a given proportion of the dosing interval ( f T > MIC) has been shown to predict clinical and microbiologic success [1]. To improve the likelihood of achieving PK/PD targets for these agents, beta-lactams are often administered as prolonged (PI) or continuous infusions (CI); though, time to activity has not been well described nor