Model‐informed precision dosing of vancomycin for rapid achievement of target area under the concentration‐time curve: A simulation study

Abstract In this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration‐time curve (AUC) of vancomycin on the first and second day (AUC0–24, AUC24–48, respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model‐informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations. Bayesian forecasting was performed to evaluate the probability of achieving the therapeutic range of AUC, defined as a ratio of estimated/reference AUC within 0.8–1.2. The Bayesian posterior probability of achieving the AUC24–48 range increased from 51.3% (a priori probability) to 77.5% after using two‐point sampling at the trough and peak on the first day. Sampling on the first day also yielded a higher Bayesian posterior probability (86.1%) of achieving the AUC0–24 range compared to the a priori probability of 60.1%. The Bayesian posterior probability of achieving the AUC at steady‐state (AUCSS) range by sampling on the first or second day decreased with decreased kidney function. We demonstrated that second‐day trough and peak sampling provided accurate AUC24–48, and first‐day sampling may assist in rapidly achieving therapeutic AUC24–48, although the AUCSS should be re‐estimated in patients with reduced kidney function owing to its unreliable predictive performance

Efficacy and Safety of Daptomycin versus Vancomycin for Bacteremia Caused by Methicillin-Resistant <i>Staphylococcus</i> <i>aureus</i> with Vancomycin Minimum Inhibitory Concentration > 1 µg/mL: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin minimum inhibitory concentration (MIC) > 1 µg/mL. We searched the PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov databases on 12 May 2020. All-cause mortality (primary outcome) and treatment success rates were compared and subgroups stratified by infection source risk level and method of vancomycin susceptibility testing were also analyzed. Seven studies (n = 907 patients) were included in this efficacy analysis. Compared with vancomycin, daptomycin treatment was associated with significantly lower mortality (six studies, odds ratio (OR) 0.53, 95% confidence interval (CI) 0.29–0.98) and higher treatment success (six studies, OR 2.20, 95% CI 1.63–2.96), which was consistent regardless of the vancomycin MIC test method used. For intermediate-risk sources, daptomycin was a factor increasing treatment success compared with vancomycin (OR 4.40, 95% CI 2.06–9.40), and it exhibited a trend toward a higher treatment success rate for high-risk sources. In conclusion, daptomycin should be considered for the treatment of bacteremia caused by MRSA with vancomycin MIC > 1 µg/mL, especially in patients with intermediate- and high-risk bacteremia sources

Efficacy and Safety of Daptomycin versus Vancomycin for Bacteremia Caused by Methicillin-Resistant Staphylococcus&nbsp;aureus with Vancomycin Minimum Inhibitory Concentration &gt; 1 &micro;g/mL: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin minimum inhibitory concentration (MIC) &gt; 1 &micro;g/mL. We searched the PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov databases on 12 May 2020. All-cause mortality (primary outcome) and treatment success rates were compared and subgroups stratified by infection source risk level and method of vancomycin susceptibility testing were also analyzed. Seven studies (n = 907 patients) were included in this efficacy analysis. Compared with vancomycin, daptomycin treatment was associated with significantly lower mortality (six studies, odds ratio (OR) 0.53, 95% confidence interval (CI) 0.29&ndash;0.98) and higher treatment success (six studies, OR 2.20, 95% CI 1.63&ndash;2.96), which was consistent regardless of the vancomycin MIC test method used. For intermediate-risk sources, daptomycin was a factor increasing treatment success compared with vancomycin (OR 4.40, 95% CI 2.06&ndash;9.40), and it exhibited a trend toward a higher treatment success rate for high-risk sources. In conclusion, daptomycin should be considered for the treatment of bacteremia caused by MRSA with vancomycin MIC &gt; 1 &micro;g/mL, especially in patients with intermediate- and high-risk bacteremia sources