Beta-lactam antibiotics in continuous infusion in critically ill patients

Abstract

We read with great interest Taccone and colleagues’ article [1], published in a recent issue of Critical Care, on the insuffi cient β-lactam concentrations in the early phase of severe sepsis and septic shock. While we fully agree with the authors’ fi ndings, we would like to off er some remarks. Only 18 of their 80 patients (22.5%) were infected with Pseudomonas aeruginosa, but Taccone and colleagues used the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimal inhibitory concentration (MIC) breakpoints of P. aeruginosa to calculate the target pharmacokinetics (PK) profi le in all of the patients. Because Enterobacteriaceae form a substantial part of infectious organisms in intensive care patients, it would be interesting to see how many patients would attain the PK profi le for these microorganisms [2]. For cefepime, for instance, if the EUCAST sensitivity threshold of 1 mg/L were used, 17 of 19 patients (89%) would attain the target PK profi le as compared with 3 of 19 patients (16%) for P. aeruginosa. Of course, we agree that, in an empirically started antibiotic regimen, the organisms, let alone the MIC, are not known to the clinician. Furthermore, the data of Taccone and colleagues should be interpreted in light of local epidemiology and resistance data. In a Belgian multicenter study, all P. aeruginosa strains isolated from patients hospitalized in the intensive care unit (ICU) had an MIC 90 (MIC required to inhibit the growth of 90% of organisms) for meropenem of 0.12 mg/L [3]. With this MIC, even more than 75% of the patients would have attained the target PK profi le. In addition, we think that the initial loading dose should be followed immediately by an extended or continuous infusion in order to obtain an optimal PK/ pharmacodynamics (PK/PD) profi le [4].