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.
Highlights
The importance of early, correct antibiotic treatment in bacterial infections is undisputed [1]
The predominant route of elimination is via the kidneys, and dosing of most betalactams is adjusted according to estimated glomerulus filtration rates
Considering the proteinbinding of each antibiotic and that meropenem therapy in patients admitted to wards of internal medicine or infectious diseases in our region is predominantly used in immunedeficient individuals, we suggest target interval of total trough concentration starting at the level of the non-species-related breakpoint
Summary
The importance of early, correct antibiotic treatment in bacterial infections is undisputed [1]. Optimizing antibiotic treatment means choosing the correct antibiotic and administering a correct dose to ensure efficacy and to minimize the risk of adverse events. The most commonly used group of antibiotics for severe infections is beta-lactams. The volume of distribution of beta-lactam antibiotics is considered similar, with the exception of small children and pregnant women [10, 11]. Volatile pharmacokinetics for beta-lactams is well documented, including severe sepsis. The volume of distribution increases, mainly due to capillary leakage and fluid resuscitation, and augmented as well as reduced renal clearance is common [2, 12]. Increasing age is associated with an increased risk of infection, but age-related changes in organ
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