Continuous infusion of meropenem in critically ill patients: practical considerations

read with interest the article from Chytra and colleagues, who investigated the eff ectiveness and safety of continuous infusion (CI) of meropenem compared with intermittent infusion (II) in a large cohort (n = 240) of critically ill patients [1]. Th ey found that although clinical cure at the end of therapy was similar between the two strategies, micro bio logical success was higher in the CI group and was independently associated with continuous drug adminis tration. CI was also associated with a shorter ICU stay, as well as shorter duration of therapy and a lower total dose of meropenem. Th is paper highlights the potential benefi ts of CI of β-lactams compared with standard adminis tration in critically ill patients, which has already been suggested in previous retrospective studies [2]. Nevertheless, some points need to be discussed. First, the doses of meropenem used by Chytra and colleagues could be largely criticized. Th e authors have already under lined how the CI strategy received a lower daily regimen than the bolus strategy (4 g/day vs. 6 g/day) and the use of such an approach showed only clinical equivalence with but not superiority to II in clinical trials [3]. More importantly, the II group was treated with higher than recommended daily regimens (2 g every 8 hours rather than 1 g every 8 hours). In severe sepsis and septic shock, a 1 g loading dose of meropenem resulted in optimal serum concentrations to treat pathogen with a minimal inhibitory concentration (MIC) of 2 μg/ml in 75% of patients, while it provided adequate drug levels for lower MICs in all patients [4]. Th e same results were shown for both loading and steady-state doses when serum and subcutaneous drug levels were measured [5]. Calculating the doses of meropenem on popu lation pharmacokinetic models from patients without critically illness may thus under esti mate antibiotic concentrations measured in real popu lations and result in unnecessarily high drug regimens. Future research should therefore consider standard drug regimens (1 g every 8 hours) as a valuable control for CI strategies in septic patients. Second, the CI group received 4 g meropenem over 24 hours, aiming to reach 100% of the time that drug concentrations would be above the MIC (T>MIC) for most Gram-negative pathogens. Nevertheless, carba pen ems need only 40% T>MIC to have bactericidal eff ects, because of the signifi cant post-antibiotic eff ect and …