Monitoring of a single post-infusion blood sample to estimate the actual peak and trough concentration of tobramycin in critically ill patients

Reimann, Ilselore R.; Meier‐Hellmann, Andreas; Traut, T.; Reinhart, Konrad; Hoffmann, A

doi:10.1078/0940-2993-00284

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…This approach would be particularly applicable to critically ill patients, given known physiological fluctuations in these patients where a single-sample approach may be less appropriate and where alternative targets (such as C max and C min ) may be considered useful to guide dosing. [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%).…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

“…This approach would be particularly applicable to critically unwell patients, given known physiological fluctuations in these patients where a single sample approach may be less appropriate. (16–19). 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.…”

Section: Discussionmentioning

confidence: 99%

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

Drennan

Thoma

Barry

et al. 2021

Preprint

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BackgroundIntravenous tobramycin requires therapeutic drug monitoring (TDM) to ensure safety and efficacy when used for prolonged treatment, as in infective exacerbations of Cystic Fibrosis (CF). The 24 hour area under the concentration time curve (AUC24) is widely used to guide dosing, however there remains variability in practice around methods for its estimation.ObjectivesTo determine the potential for a sparse sampling strategy using a single post-infusion tobramycin concentration and Bayesian forecasting, to assess the AUC24 in routine practice.MethodsAdults with CF receiving once daily tobramycin had paired concentrations measured 2 hours (c1) and 6 hours (c2) following end of infusion as routine monitoring. We estimated AUC24 exposures using Tucuxi, a Bayesian forecasting application incorporating a validated population pharmacokinetic model. We performed simulations to estimate AUC24 using the full dataset using c1 and c2, compared to estimates using depleted datasets (c1 or c2 only), with and without concentration data from earlier in the course. We assessed agreement between each simulation condition and the reference graphically, and numerically using median difference (Δ) AUC24, and (relative) root mean square error (rRMSE) as measures of bias and accuracy respectively.Results55 patients contributed 512 concentrations from 95 tobramycin courses and 256 TDM episodes. Single concentration methods performed well, with median ΔAUC24 <2 mg.h.l-1 and rRMSE of <15% for sequential c1 and c2 conditions.ConclusionsBayesian forecasting, using single post-infusion concentrations taken 2-6 hours following tobramycin administration can adequately estimate true exposure in this patient group and are suitable for routine TDM practice.Key Points-In stable adult patients with Cystic fibrosis without significant renal impairment, Bayesian forecasting allows accurate estimation of tobramycin AUC24 using a single blood sample taken 2-6 hours post-infusion with acceptable accuracy, especially when including prior measured concentrations.-A single sample approach with Bayesian forecasting is logistically less complicated than a two-sample approach, and could facilitate best-practice TDM in the outpatient setting.-A more intensive sampling strategy with Bayesian forecasting using two tobramycin concentrations in a dosing interval should be considered in unstable patients, or where observed concentrations deviate significantly from model predictions.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Drennan

Thoma

Barry

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…This approach would be particularly applicable to critically ill patients, given known physiological fluctuations in these patients where a single-sample approach may be less appropriate and where alternative targets (such as C max and C min ) may be considered useful to guide dosing. 17–21 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%).…”

Section: Discussionmentioning

confidence: 96%

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

Drennan

Thoma

Barry

et al. 2021

Therapeutic Drug Monitoring

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Background: Intravenous tobramycin treatment requires therapeutic drug monitoring (TDM) to ensure safety and efficacy when used for prolonged treatment, as in infective exacerbations of cystic fibrosis. The 24-hour area under the concentration–time curve (AUC24) is widely used to guide dosing; however, there remains variability in practice around methods for its estimation. The objective of this study was to determine the potential for a sparse-sampling strategy using a single postinfusion tobramycin concentration and Bayesian forecasting to assess the AUC24 in routine practice. Methods: Adults with cystic fibrosis receiving once-daily tobramycin had paired concentrations measured 2 hours (c1) and 6 hours (c2) after the end of infusion as routine monitoring. AUC24 exposures were estimated using Tucuxi, a Bayesian forecasting application that incorporates a validated population pharmacokinetic model. Simulations were performed to estimate AUC24 using the full data set using c1 and c2, compared with estimates using depleted data sets (c1 or c2 only), with and without concentration data from earlier in the course. The agreement between each simulation condition and the reference was assessed graphically and numerically using the median difference (∆) AUC24 and (relative) root mean square error (rRMSE) as measures of bias and accuracy, respectively. Results: A total of 55 patients contributed 512 concentrations from 95 tobramycin courses and 256 TDM episodes. Single concentration methods performed well, with median ∆AUC24 <2 mg·h·L−1 and rRMSE of <15% for sequential c1 and c2 conditions. Conclusions: Bayesian forecasting implemented in Tucuxi, using single postinfusion concentrations taken 2–6 hours after tobramycin administration, yield similar exposure estimates to more intensive (two-sample) methods and are suitable for routine TDM practice.

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“…Arbekacin therapy of critically ill patients requires careful dosing to achieve effective drug concentrations and to avoid toxic effects. Renal toxicity of aminoglycosides may increase in patients with pre-existing renal impairment (19). These issues should be taken into account when using ABK to ensure adequate serum levels (20).…”

Section: Limitations Of the Studymentioning

confidence: 99%

Recommended dose of arbekacin, an aminoglycoside against methicillin-resistantStaphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance

Fukuoka

Aibiki

2008

Journal of Clinical Pharmacy and Therapeutics

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Monitoring of a single post-infusion blood sample to estimate the actual peak and trough concentration of tobramycin in critically ill patients

Cited by 4 publications

References 19 publications

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

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

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

Recommended dose of arbekacin, an aminoglycoside against methicillin-resistantStaphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance

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