Continuous Infusion of Beta-Lactam Antibiotics is Superior to Intermittent Dosing for Sepsis

The bactericidal activity of antibiotics depends on the class of antibiotic used. Some antibiotics like vancomycin, aminoglycosides and fluoroquinolones are dose-dependent for their bactericidal activity. Other antibiotics like beta-lactam antibiotics are time-dependent antibiotics.  Time-dependent antibiotics have increased bactericidal activity the more time the drug concentrations are at or above the minimal inhibitory concentration of the bacteria causing the infection.

Thus, it makes theoretical sense that prolonged infusions of beta-lactam antibiotics could increase bactericidal activity of beta-lactams vs standard dosing.  Typically, beta-lactam antibiotics are infused over about 30 minutes.  Prolonged infusions run for several hours.

This meta-analysis analyzed 632 patients from three randomized trials to compare a continuous-infusion of β-lactams compared with intermittent dosing in critically ill patients with severe sepsis or septic shock. Continuous-infusion dosing significantly lowered 30-day mortality (relative risk, 0.73; number needed to treat [NNT], 15). For piperacillin-tazobactam (Zosyn) specifically, continuous infusion compared with intermittent dosing significantly lowered mortality (RR, 0.63; NNT, 11).

Although continuous infusions are clearly superior to standard short infusions for beta-lactams in septic patients, continuous infusions also take up one IV port constantly.  A more practical solution especially for piperacillin-tazobactam is to infuse the medication for 3 hours every 6 hours.  This still provides a concentration of the beta-lactam above the MIC for the vast majority of the day, but frees up the IV for other meds about 50% of the time.


Roberts JA et al. Continuous versus intermittent β-lactam infusion in severe sepsis. A meta-analysis of individual patient data from randomized trials. Am J Respir Crit Care Med 2016 Sep 15; 194:681.

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