Basic pharmacokinetics-pharmacodynamics model with different modes of administration. Compared with traditional intermittent (lower alternating line) and continuous infusion without loading dose (steadily rising line), delay is to be expected in reaching rapid target attainment in the early phase of severe sepsis and/or shock (ellipse at lower left). Target concentrations can be rapidly achieved by administration of a loading dose (1–2 grams in 30 minutes), followed within 1–2 hours by high-dose prolonged infusion (upper alterating line). Note that time above the minimal inhibitory concentration (MIC) is 100% and a multiple of MIC, maximizing the time to acylate penicillin-binding proteins and suppress resistance.