Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia

The bactericidal activity of β-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T > MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study was a randomised, three-way, cross-over design in eight febrile neutropenic patients with bacteraemia. Each subject received meropenem in three regimens consecutively: (i) a bolus injection of 1 g every 8 h (q8h) for 24 h; (ii) a 3-h infusion of 1 g q8h for 24 h; and (iii) a 3-h infusion of 2 g q8h for 24 h. For pathogens with an MIC of 4 μg/mL, the PTA of achieving 40% T > MIC following administration of meropenem by a bolus injection of 1 g q8h, a 3-h infusion of 1 g q8h and a 3-h infusion of 2 g q8h was 75.7%, 99.24% and 99.96%, respectively. Only the 3-h infusion of 2 g q8h achieved a PTA >99% for 40% T > MIC for a MIC of 8 μg/mL. By referral to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC distributions, the three regimens of meropenem were predicted to achieve a CFR ≥ 90% against Escherichia coli and Klebsiella spp. In conclusion, a 3-h infusion of 2 g of meropenem q8h resulted in the highest PTA rates. The three regimens of meropenem had high probabilities of achieving optimal impact against E. coli and Klebsiella spp.