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Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

ABSTRACT: BACKGROUND:Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the Cmax should be 64-80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target Cmax/MIC???8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. METHODS:Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and Cmax measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min-max]. RESULTS:93 patients with 98 GNB-documented infections were included. The median Cmax was 55.2 mg/L [12.2-165.7] and the median MIC was 2 mg/L [0.19-16]. Cmax/MIC ratio???8 was achieved in 87 patients (88.8%) while a Cmax???64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between Cmax/MIC ratio and clinical outcome at D8 and D28. CONCLUSION:According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.

SUBMITTER: Logre E

PROVIDER: S-EPMC7276966 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

Logre Elsa E Enser Maya M Tanaka Sébastien S Dubert Marie M Claudinon Aurore A Grall Nathalie N Mentec Hervé H Montravers Philippe P Pajot Olivier O

Annals of intensive care 20200608 1

<h4>Background</h4>Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (C<sub>max</sub>) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the C<sub>max</sub> should be 64-80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target C<sub>max</sub>/MIC ≥ 8 using the me ...[more]

PMID: 32514769

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Project description:ObjectiveTo study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strategies.MethodsMicafungin PK data from 20 intensive care unit patients were available. A population-PK model was developed. Various dosing regimens were simulated: licensed regimens (I) 100 mg daily; (II) 100 mg daily with 200 mg from day 5; and adapted regimens 200 mg on day 1 followed by (III) 100 mg daily; (IV) 150 mg daily; and (V) 200 mg daily. Target attainment based on a clinical PK target for Candida as well as non-Candida parapsilosis infections was assessed for relevant minimum inhibitory concentrations [MICs] (Clinical and Laboratory Standards Institute). Parameter uncertainty was taken into account in simulations.ResultsA two-compartment model best fitted the data. Clearance was 1.10 (root square error 8%) L/h and V 1 and V 2 were 17.6 (root square error 14%) and 3.63 (root square error 8%) L, respectively. Median area under the concentration-time curve over 24 h (interquartile range) on day 14 for regimens I-V were 91 (67-122), 183 (135-244), 91 (67-122), 137 (101-183) and 183 (135-244) mg h/L, respectively, for a typical patient of 70 kg. For the MIC/area under the concentration-time curve >3000 target (all Candida spp.), PK target attainment was >91% on day 14 (MIC 0.016 mg/L epidemiological cut-off) for all of the dosing regimens but decreased to (I) 44%, (II) 91%, (III) 44%, (IV) 78% and (V) 91% for MIC 0.032 mg/L. For the MIC/area under the concentration-time curve >5000 target (non-C. parapsilosis spp.), PK target attainment varied between 62 and 96% on day 14 for MIC 0.016.ConclusionsThe licensed micafungin maintenance dose results in adequate exposure based on our simulations with a clinical PK target for Candida infections but only 62% of patients reach the target for non-C. parapsilosis. In the case of pathogens with an attenuated micafungin MIC, patients may benefit from dose escalation to 200 mg daily. This encourages future study.

Project description:Purpose: To determine whether inotrope administration is associated with increased all-cause mortality in cardiogenic shock (CS) patients and to identify inotropes superior for improving mortality. Methods: This retrospective cohort study analyzed data retrieved from the Philips Electronic ICU (eICU) database, a clinical database of 200,859 patients from over 208 hospitals located throughout the United States. The database was searched for patients admitted with CS to the intensive care unit (ICU) between 2014 and 2015. We evaluated 34,381 CS patients. They were classified into the inotrope and non-inotrope groups based on whether inotropes were administered during hospitalization. The primary endpoint was all-cause hospital mortality. Findings: In total, 15,021 (43.69%) patients received inotropes during hospitalization. The in-hospital mortality rate was significantly higher in the inotrope group than in the non-inotrope group (2,999 [24.03%] vs. 1,547 [12.40%], adjusted hazard ratio: 2.24; 95% confidence interval [CI]: 2.09-2.39; p < 0.0001). After propensity score matching according to the cardiac index, 359 patients were included in each group. The risk of ICU (OR 5.65, 95% CI, 3.17-10.08, p < 0.001) and hospital (OR 2.63, 95% CI: 1.75-3.95, p < 0.001) mortality in the inotrope group was significantly higher. In the inotrope group, the administration of norepinephrine ≤0.1 μg/kg/min and dopamine ≤15 μg/kg/min did not increase the risk of hospital mortality, and milrinone administration was associated with a lower mortality risk (odds ratio: 0.559, 95% CI: 0.430-0.727, p < 0.001). Meanwhile, the administration of >0.1 μg/kg/min dobutamine, epinephrine, and norepinephrine and dopamine >15 μg/kg/min was associated with a higher risk of hospital mortality. Conclusions: Inotropes should be used cautiously because they may be associated with a higher risk of mortality in CS patients. Low-dose norepinephrine and milrinone may associated with lower risk of hospital mortality in these patients, and supportive therapies should be considered when high-dose inotropes are administered.

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Project description:PurposeThe final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge.MethodsPatients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors).ResultsNon-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771-0.890) for PCT, 0.688 (0.566-0.810) for albumin, 0.861 (0.796-0.927) for SOFA score, and increased to 0.913 (0.858-0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis.ConclusionsSerum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction.

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Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

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Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

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