A systematic review on clinical benefits of continuous administration of β-lactam antibiotics*

OBJECTIVE: The clinical benefits of extended infusion or continuous infusion of beta-lactam antibiotics remain controversial. We systematically reviewed the literature to determine whether any clinical benefits exist for administration of beta-lactam antibiotics by extended or continuous infusion. DATA SOURCE: PubMed (January 1950 to November 2007), EMBASE (1966 to November 2007), and the Cochrane Controlled Trial Register were searched (updated November 2007). STUDY SELECTIONS: Randomized controlled trials (RCTs) were meta-analyzed, and observational studies were described by two unblinded reviewers. DATA EXTRACTION: A total of 846 patients from eligible prospective randomized controlled studies were included in the meta-analysis. Two observational studies were deemed appropriate for description. DATA SYNTHESIS: A meta-analysis of prospective RCTs was undertaken using Review Manager. Among a total of 59 potentially relevant studies, 14 RCTs involving a total of 846 patients from nine countries were deemed appropriate for meta-analysis. The use of continuous infusion of a beta-lactam antibiotic was not associated with an improvement in clinical cure (n = 755 patients; odds ratio: 1.04, 95% confidence interval: 0.74-1.46, p = 0.83, I = 0%) or mortality (n = 541 patients; odds ratio: 1.00, 95% confidence interval: 0.48-2.06, p = 1.00, I = 14.8%). All RCTs except one used a higher antibiotic dose in the bolus administration group. Two observational studies, not pooled because they did not meet the a priori criteria for meta-analysis, showed that beta-lactam administration by extended or continuous infusion was associated with an improvement in clinical cure. The difference in the results between the meta-analysis results and the observational studies could be explained by the bias created by a higher dose of antibiotic in the bolus group in the RCTs and because many of the RCTs only recruited patients with a low acuity of illness. CONCLUSIONS: The limited data available suggest that continuous infusion of beta-lactam antibiotics leads to the same clinical results as higher dosed bolus administration in hospitalized patients.