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
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 dalbava...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/8/996 |
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| author | Pier Giorgio Cojutti Sara Tedeschi Milo Gatti Eleonora Zamparini Marianna Meschiari Paola Della Siega Maria Mazzitelli Laura Soavi Raffaella Binazzi Elke Maria Erne Marco Rizzi Anna Maria Cattelan Carlo Tascini Cristina Mussini Pierluigi Viale Federico Pea |
| author_facet | Pier Giorgio Cojutti Sara Tedeschi Milo Gatti Eleonora Zamparini Marianna Meschiari Paola Della Siega Maria Mazzitelli Laura Soavi Raffaella Binazzi Elke Maria Erne Marco Rizzi Anna Maria Cattelan Carlo Tascini Cristina Mussini Pierluigi Viale Federico Pea |
| author_sort | Pier Giorgio Cojutti |
| collection | DOAJ |
| description | 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 <i>f</i>AUC<sub>24h</sub>/MIC > 111.1 against <i>S. aureus</i>) 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 (CL<sub>CR</sub>) 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. |
| first_indexed | 2024-03-09T04:47:14Z |
| format | Article |
| id | doaj.art-beedcb1e8eff4f9a9fd797e2daabd03f |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T04:47:14Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-beedcb1e8eff4f9a9fd797e2daabd03f2023-12-03T13:14:08ZengMDPI AGAntibiotics2079-63822022-07-0111899610.3390/antibiotics11080996Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug MonitoringPier Giorgio Cojutti0Sara Tedeschi1Milo Gatti2Eleonora Zamparini3Marianna Meschiari4Paola Della Siega5Maria Mazzitelli6Laura Soavi7Raffaella Binazzi8Elke Maria Erne9Marco Rizzi10Anna Maria Cattelan11Carlo Tascini12Cristina Mussini13Pierluigi Viale14Federico Pea15Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyInfectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyClinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyInfectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDepartment of Infectious Diseases and Tropical Medicine, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, ItalyInfectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, 33100 Udine, ItalyInfectious and Tropical Diseases Unit, Padua University Hospital, 35128 Padua, ItalyUOC Malattie Infettive, ASST Papa Giovanni XXIII, 24127 Bergamo, ItalyUOC Malattie Infettive, Azienda Sanitaria dell’Alto Adige, 39100 Bolzano, ItalyUOC Malattie Infettive, Azienda Sanitaria dell’Alto Adige, 39100 Bolzano, ItalyUOC Malattie Infettive, ASST Papa Giovanni XXIII, 24127 Bergamo, ItalyInfectious and Tropical Diseases Unit, Padua University Hospital, 35128 Padua, ItalyInfectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, 33100 Udine, ItalyDepartment of Infectious Diseases and Tropical Medicine, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, ItalyInfectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyClinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyA 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 <i>f</i>AUC<sub>24h</sub>/MIC > 111.1 against <i>S. aureus</i>) 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 (CL<sub>CR</sub>) 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.https://www.mdpi.com/2079-6382/11/8/996dalbavancinpopulation pharmacokineticstherapeutic drug monitoringlong-term treatmentoff-label use |
| spellingShingle | Pier Giorgio Cojutti Sara Tedeschi Milo Gatti Eleonora Zamparini Marianna Meschiari Paola Della Siega Maria Mazzitelli Laura Soavi Raffaella Binazzi Elke Maria Erne Marco Rizzi Anna Maria Cattelan Carlo Tascini Cristina Mussini Pierluigi Viale Federico Pea 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 Antibiotics dalbavancin population pharmacokinetics therapeutic drug monitoring long-term treatment off-label use |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | dalbavancin population pharmacokinetics therapeutic drug monitoring long-term treatment off-label use |
| url | https://www.mdpi.com/2079-6382/11/8/996 |
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