Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring

Abstract

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration–time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Fast and Simple Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Dalbavancin in Long-Term Treatment of Subacute and/or Chronic Infections

“…897/2021/Oss/AOUBo on 29 November 2021]. Informed written consent was waived due to the retrospective and observational nature of the study [ 2 , 3 ]. The number of samples assessed was 520.…”

“…Samples for Dalbavancin TDM were usually collected at predefined timeframes between 21 and 35 days after first administration. More details on this may be found in our previous study [ 3 ]. Blood samples respected the cold chain delivery and were processed either immediately after delivery or after freezing at −80 °C until analysis, depending on case-by-case.…”

“…Thanks to the very long elimination half-life, DBV is being increasingly used in clinical practice for the long-term treatment of a wide range of subacute and/or chronic infections, mainly osteo-articular infections (OAI). Population pharmacokinetic studies showed that two 1500 mg DBV doses 1 week apart could ensure effective treatment for several weeks [ 2 , 3 ]. However, it could be quite difficult establishing which could be the real duration of effective treatment due to the wide interindividual pharmacokinetic variability observed in this clinical scenario [ 2 , 3 ].…”

“…Population pharmacokinetic studies showed that two 1500 mg DBV doses 1 week apart could ensure effective treatment for several weeks [ 2 , 3 ]. However, it could be quite difficult establishing which could be the real duration of effective treatment due to the wide interindividual pharmacokinetic variability observed in this clinical scenario [ 2 , 3 ]. Therapeutic drug monitoring (TDM) can be a helpful tool for providing clinicians with real-time feedback on real duration of optimal treatment by assessing DBV concentrations over time in each single patient [ 2 , 3 ].…”

“…However, it could be quite difficult establishing which could be the real duration of effective treatment due to the wide interindividual pharmacokinetic variability observed in this clinical scenario [ 2 , 3 ]. Therapeutic drug monitoring (TDM) can be a helpful tool for providing clinicians with real-time feedback on real duration of optimal treatment by assessing DBV concentrations over time in each single patient [ 2 , 3 ]. Nowadays, TDM is considered the only effective and safe way for optimizing exposure with antimicrobials, especially in critically ill patients [ 4 , 5 ].…”