ABSTRACT
Posaconazole, systemic antifungal marketed in France since 2006, is indicated as second line in curative treatment of invasive fungal infections (IFI) (aspergillosis...) and prophylaxis of IFI in patients receiving chemotherapy or hematopoietic stem cell transplantation. The analysis of the literature indicates a concentration-efficacy relationship, but to date, no study has been able to show a concentration-toxicity correlation due to its favourable safety profile and the difficulty to obtain high concentrations. In curative, maintenance of trough plasma concentrations between 0.5 and 1.5 mg/L seems to be associate with an efficacy. In prophylaxis, a threshold of 0.5 mg/L corresponds to a minimal exposure. However this target is not yet well defined. Saturation of absorption above the 800 mg oral dose limits the adjustment of concentrations. As such, the Therapeutic Drug Monitoring of posaconazole can be recommended.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Mycoses/drug therapy , Triazoles/chemistry , Triazoles/therapeutic use , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/economics , Antifungal Agents/pharmacokinetics , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Drug Interactions , Drug Monitoring , Evidence-Based Medicine , Humans , Mycoses/prevention & control , Spectrophotometry, Ultraviolet , Triazoles/administration & dosage , Triazoles/adverse effects , Triazoles/economics , Triazoles/pharmacokineticsABSTRACT
Vancomycin is an antibiotic for exclusive hospital use administrated in intravenous infusion to treat systemic infections. It is mainly eliminated by kidneys and potentially nephrotoxic. Data available show that Therapeutic Drug Monitoring (TDM) of vancomycin is highly recommended. It aims to ensure efficacy and avoid resistance by maintaining trough plasma concentrations above the MIC. Secondary, vancomycine TDM may be indicated to prevent nephrotoxicity in high risk patients. TDM is often underwent at steady state (48 to 72 h after the treatment initiation) unless in case of renal impairment (24 h). While compared with intermittent administration, continuous infusion did not result in prognosis improvement; however it resulted in lower pharmacokinetic variability and better cost-efficiency. Targeted trough concentrations for intermittent infusion are between 15 and 20 mg/L (up to 25-30 mg/L for GISA). In case of continuous infusion, targets are higher (25 to 40 mg/L).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Monitoring/methods , Vancomycin/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/economics , Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/economics , Bacterial Infections/microbiology , Dose-Response Relationship, Drug , Evidence-Based Medicine , Humans , Infusions, Intravenous , Kidney Diseases/complications , Kidney Diseases/metabolism , Vancomycin/administration & dosage , Vancomycin/adverse effects , Vancomycin/economics , Vancomycin/pharmacokineticsABSTRACT
Level of Evidence for Therapeutic Drug Monitoring of Vancomycin. Vancomycin is an antibiotic for exclusive hospital use administrated in intravenous infusion to treat systemic infections. It is mainly eliminated by kidneys and potentially nephrotoxic. Data available show that Therapeutic Drug Monitoring (TDM) of vancomycin is highly recommended. It aims to ensure efficacy and avoid resistance by maintaining trough plasma concentrations above the MIC. Secondary, vancomycine TDM may be indicated to prevent nephrotoxicity in high risk patients. TDM is often underwent at steady state (48 to 72 h after the treatment initiation) unless in case of renal impairment (24 h). While compared with intermittent administration, continuous infusion did not result in prognosis improvement; however it resulted in lower pharmacokinetic variability and better cost-efficiency. Targeted trough concentrations for intermittent infusion are between 15 and 20 mg/L (up to 25-30 mg/L for GISA). In case of continuous infusion, targets are higher (25 to 40 mg/L).
ABSTRACT
Posaconazole, systemic antifungal marketed in France since 2006, is indicated as second line in curative treatment of invasive fungal infections (IFI) (aspergillosis. . . ) and prophylaxis of IFI in patients receiving chemotherapy or hematopoietic stem cell transplantation. The analysis of the literature indicates a concentration-efficacy relationship, but to date, no study has been able to show a concentration-toxicity correlation due to its favourable safety profile and the difficulty to obtain high concentrations. In curative, maintenance of trough plasma concentrations between 0.5 and 1.5 mg/L seems to be associate with an efficacy. In prophylaxis, a threshold of 0.5 mg/L corresponds to a minimal exposure. However this target is not yet well defined. Saturation of absorption above the 800 mg oral dose limits the adjustment of concentrations. As such, the Therapeutic Drug Monitoring of posaconazole can be recommended.
