Continuous infusion of beta-lactams.
OBJECTIVE
Continuous infusion of beta-lactam antibiotics is becoming increasingly popular. The background and current clinical evidence are discussed. Tools to apply continuous infusion are analyzed.


RESULTS
One randomized controlled trial in an ICU setting and two nonrandomized controlled trials have shown continuous infusion to be more beneficial than intermittent infusion. One randomized controlled trial in chronic obstructive pulmonary disorder patients, however, showed no difference between the two treatments. The stability of most beta-lactams for use during continuous infusion has been documented.


CONCLUSIONS
Killing of bacteria by beta-lactam antibiotics is maximal at around four times the minimum inhibitory concentration in vitro. To ensure an optimal effect when treating severe infections, free unbound concentrations at or above four times the minimum inhibitory concentration should be maintained. Although continuous infusion has been demonstrated to be superior in animal studies, randomized clinical trials have failed to confirm this in humans, primarily because of suboptimal design. A better designed randomized clinical trial, set up as a pilot study, recently demonstrated a favorable outcome with continuous infusion. A major issue during continuous infusion is the stability of the antibiotic, which may limit its application. The calculation of the infusion rate necessary to obtain the desired free drug concentration is relatively straightforward.
Mouton
Johan W
JW
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. mouton@cwz.nl
Vinks
Alexander A
AA
D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D047090:beta-Lactams / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D047090:beta-Lactams