196,049 research outputs found
Daptomycin underexposure in a young intravenous drug user who was affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection associated with bacteraemia
No full textWe describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean ± standard deviation: Cmin 12.35 ± 0.80 mg/L, C max 63.90 ± 8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug monitoring may be helpful for optimizing daptomycin exposure in these patients. Physicians should take into account that dosages much higher than the standard ones may be needed, probably as a consequence of augmented drug clearanc
Treatment of consecutive episodes of multidrug-resistant bacterial pleurisy with different aetiology in a heart transplant candidate: Proof of concept of pharmacokinetic/pharmacodynamic optimisation of antimicrobial therapy at the infection site
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Prospectively validated dosing nomograms for maximizing the pharmacodynamics of vancomycin administered by continuous infusion in critically ill patients
No full textThe efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CLCr) estimates for use in daily clinical practice to target the steady-state concentrations (Csss) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CL v) and CLCr was retrospectively assessed in a cohort of critically ill patients (group 1, n = 70) to create a formula for dosage calculation to target Css at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2, n = 63) by comparison of the observed and the predicted Csss. A significant relationship between CLv and CLCr was observed in group 1 (P < 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 x CLCr (ml/min) + 0.94] + target Css x (24/1,000)} led to a significant correlation between the observed and the predicted Csss (r = 0.80, P < 0.001). Two dosing nomograms based on CLCr were created to target the vancomycin Css at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin. Copyright © 2009, American Society for Microbiology. All Rights Reserved
Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?
No full textThe effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio (Css/MIC) of 1–4. Univariate binary logistic regression analysis was performed to identify independent predictors of clinical outcome. Among the 30 eligible patients, 53.3% had infections caused by meropenem-resistant KPC-Kp (MIC ≥ 16 mg/L). Tigecycline and colistin were the two antimicrobials most frequently combined with meropenem. Mean doses of continuous-infusion meropenem ranged from 1.7 to 13.2 g/daily. The Css/MIC ratio was ≥1 in 73.3% of cases and ≥4 in 50.0%. Clinical outcome was successful in 73.3% of cases after a median treatment length of 14.0 days. In univariate analysis, a significant correlation with successful clinical outcome was found for a Css/MIC ratio ≥1 (OR = 10.556, 95% CI 1.612–69.122; P = 0.014), a Css/MIC ratio ≥4 (OR = 12.250, 95% CI 1.268–118.361; P = 0.030) and a Charlson co-morbidity index of ≥4 (OR = 0.158, 95% CI 0.025–0.999; P = 0.05). High-dose continuous-infusion meropenem optimised by means of real-time TDM may represent a valuable tool in improving clinical outcome when dealing with the treatment of infections caused by KPC-Kp with a meropenem MIC ≤ 64 mg/L
Erratum to: Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation [Biol Blood Marrow Transplant (2017) 23 (333–339)] (S1083879116304839) (10.1016/j.bbmt.2016.11.005)
No full textIn the above-mentioned article, the third author's name was printed incorrectly. The correct author name should read Massimo Dozzo
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