Considerable variation of trough β-lactam concentrations in older adults hospitalized with infection-a prospective observational study

Abstract

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

Fig. 1

Spaghetti plots illustrating the variation in total trough antibiotic concentration levels in the patients from whom two values were obtained. The dashed lines mark the reference interval used for target concentration levels (non-species-related breakpoint − 5× non-species-related breakpoint). a Cefotaxime values (target interval used 1–5 mg/L or μg/mL). b Piperacillin values (target interval used 4–20 mg/L or μg/mL). c Meropenem values (target interval 2–10 mg/L or μg/mL)