Achieving target plasma concentrations of beta-lactam antibiotics in critically ill patients: a retrospective study of full-dose administration in the first 24 hours.

BACKGROUND

Beta-lactams are the cornerstone of therapy for the treatment of the most serious infections in the intensive care unit (ICU) setting. However, individualization of dosing remains challenging because pharmacokinetics are highly variable and difficult to predict in critically ill patients. The objective of this study was to evaluate whether administration of full-dose beta-lactam antibiotics to critically ill subjects during the first 24 h of treatment, irrespective of baseline renal function, achieves predefined target concentration ranges (Cmin [free minimum concentration] 1–10 × MIC [minimum inhibitory concentration] and 4–10 × MIC).

METHODS

This trial was a retrospective, observational cohort study. A total of 377 critically ill patients over 18 years admitted to the ICU who received full doses of meropenem, piperacillin–tazobactam, or cefepime were analyzed. Blood sampling for determination of antibiotic trough concentration was performed 24 h after initiation of full-dose therapy.

RESULTS

When targeting a Cmin of 4–10 × MIC, a high proportion of patients remained underdosed (42.7%, N = 161). In contrast, when targeting a Cmin of 1–10 × MIC, only 13.3% (N = 50) of patients failed to reach the target range. Seventy-four patients (19.6%) were found to be above the defined target range (Cmin > 10 × MIC). Reduced glomerular filtration rate (GFR) was a consistent independent predictor of achieved plasma level across the overall population, as well as within individual subsets. No adverse effects (neurotoxicity, hematotoxicity, hepatotoxicity) were observed.

CONCLUSIONS

With full-dose beta-lactam administration, targeting a Cmin of 4–10 × MIC results in a high proportion of patients being underdosed, whereas a target of 1–10 × MIC is achieved in the majority of patients. Our results highlight the importance of therapeutic drug monitoring (TDM) of beta-lactam antibiotics in critically ill patients. Further research in this field is warranted. CLINICAL TRIAL NUMBER: Not applicable.