Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics

Minerva Anestesiol. 2012 Jan;78(1):94-104. Epub 2011 Jul 6.

Abstract

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / etiology
  • Bacterial Infections / mortality
  • Child
  • Critical Care
  • Critical Illness
  • Cystic Fibrosis / complications
  • Fever / drug therapy
  • Fever / etiology
  • Humans
  • Infusions, Intravenous
  • Length of Stay
  • Leukocyte Count
  • Neoplasms / complications
  • Respiration, Artificial
  • Treatment Outcome
  • beta-Lactams / administration & dosage*
  • beta-Lactams / adverse effects
  • beta-Lactams / pharmacokinetics
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactams