International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Feb 2017
Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?
The 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. ⋯ 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.
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Int. J. Antimicrob. Agents · Feb 2017
Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis.
When treating critically ill patients with gentamicin for severe infection, peak concentrations (Cmax) determine clinical efficacy and trough concentrations (Cmin) determine toxicity. Despite administration of body weight-standardised starting doses, a wide range of Cmax is generally observed. Furthermore, in therapeutic drug monitoring, several measures of renal function are used to predict appropriate Cmin and gentamicin dosing intervals, but the most accurate predictor is not known. ⋯ In conclusion, low albumin concentrations resulted in a larger Vd and lower Cmax of gentamicin. These results suggest that use of a higher gentamicin starting dose in critically ill patients with hypoalbuminaemia may prevent underdosing. Urinary CalcCLCr is a better predictor of Cmin than SCr or CGCLCr.