In this episode, I’ll discuss the risk factors for not attaining target beta-lactam levels in ICU patients.
For beta-lactam antibiotics, an adequate time above the MIC is essential to achieve clinical success. However, critically ill patients undergo physiologic changes that may make achieving adequate time above MIC difficult. This includes alterations in fluid status, albumin levels, and augmented renal function. The lack of readily available therapeutic drug monitoring for beta-lactams, and the heterogeneity of ICU patients make addressing this problem difficult. Until there are changes in available resources to therapeutic drug monitoring, it may be helpful to identify patients who are at high risk for not attaining target beta-lactam levels with usual antibiotic doses.
A recent 2-center prospective study that examined this issue was published in the journal Critical Care. 147 critically ill patients receiving beta-lactams were analyzed. The study was in the Netherlands and most but not all antibiotics that were evaluated are available in the US: Amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem.
About two-thirds of patients achieved 100% of the time above the MIC, and about one-third achieved 100% of the time four-fold above the MIC. These cutoff levels have previously been proposed as targets that represent adequate antibiotic dosing.
Multivariate regression analysis was then applied to the results to identify patient risk factors that were associated with failure to attain target drug levels.
Male gender was significantly correlated with target non-attainment with an odds ratio of 0.32. So was a baseline eGFR ≥ 90 mL/min/1.73 m^2, with an odds ratio of 0.14 and a high BMI with an odds ratio of 0.91.
In the pre-specified secondary outcomes, target attainment was positively associated with improved ICU LOS and 30-day survival.
The authors recommend using therapeutic drug monitoring in patients with these risk factors who are receiving beta-lactam antibiotics. Unfortunately, this strategy cannot be implemented in most hospitals. Possible alternatives include extended infusion or even continuous infusion of beta-lactams in critically ill patients with risk factors for target non-attainment.
Therapeutic drug monitoring may very well be in the future for beta-lactam therapy in critically ill patients. Until then, simple risk factors assessed at the bedside such as gender and kidney function may allow for better decision-making in antibiotic dose choices to allow more patients to achieve pharmacodynamic target levels with beta-lactam antibiotics.
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