Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

Abstract

Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

Bayesian Forecasting for Intravenous Tobramycin Dosing in Adults With Cystic Fibrosis Using One Versus Two Serum Concentrations in a Dosing Interval

“…[17][18][19][20][21] Similarly, in stable patients, significantly discrepant concentrations from those expected either relative to previous estimates or predicted on the population pharmacokinetics should prompt careful consideration of a preanalytical source of error. 22 Although a more limited sampling approach resulted in less accurate pharmacokinetic parameter estimation relative to the reference, the effect was usually small (rRMSE ,15%). Although there is no established standard for acceptable accuracy in this context, it is of comparable magnitude to the accepted target ranges used in clinical practice.…”

Bayesian forecasting for intravenous tobramycin dosing in adults with Cystic Fibrosis using one versus two serum concentrations in a dosing interval

“…Similarly, in stable patients, significantly discrepant concentrations from those expected either relative to previous estimates or predicted on the population pharmacokinetics should prompt careful consideration of a pre-analytical source of error. (20)…”