Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock

BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C (max))/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients suffering from severe sepsis or septic shock. In clinical practice, the recommended target is an amikacin C (max) between 60 and 80 mg/L, which corresponds to approximately 8 times the MIC breakpoint, as defined by the European Committee on Antimicrobial Susceptibility Testing. The aim of this study was to assess the incidence and impact on mortality of an amikacin concentration between 60 and 80 mg/L in patients suffering from severe sepsis or septic shock. METHODS: This was a prospective observational cohort study conducted in two intensive care units (ICU). Patients receiving amikacin at a loading dose of 30 mg/kg for severe sepsis or septic shock were enrolled in the cohort. The target C (max) for amikacin was between 60 and 80 mg/L, as recommended by French guidelines (i.e. C (max)/MIC breakpoint = 8–10). RESULTS: Over the study period, the amikacin C (max) was <60 mg/L, between 60 and 80 mg/L, and >80 mg/L in 20 (18.2%), 46 (41.8%) and 44 (40%) of the 110 selected patients, respectively. Mortality rate was 40, 28.3 and 56.8% in the groups of patients with C (max) < 60 mg/L, 60 mg/L < C (max) < 80 mg/L and C (max) > 80 mg/L, respectively. Following multivariate analysis, mortality rate was significantly lower in the group of patients with amikacin C (max) between 60 and 80 mg/L than in the group of patients with amikacin C (max) > 80 mg/L (P = 0.004). The multivariate analysis also revealed that the factors independently associated with a higher in-ICU mortality rate were age (P = 0.02) and norepinephrine dose (P = 0.0001). CONCLUSIONS: With a loading dose of 30 mg/kg of amikacin, concentration was potentially suboptimal (C (max) < 60 mg/L) in only 18.2% of patients. The pharmacodynamic target (60 mg/L < C (max) < 80 mg/L) recommended by French guidelines was reached in 41.8% of patients and was associated with reduced in-ICU mortality. But amikacin overexposure (i.e. C (max) > 80 mg/L) was frequent and potentially associated with increased mortality

Rural-urban variation in incidence of psychosis in France: a prospective epidemiologic study in two contrasted catchment areas.

International audienceBACKGROUND: The aim of our study is to provide data on the incidence of psychotic disorders in France and compare the incidence rates in populations with different levels of urbanization. METHODS: We prospectively included the incident cases of psychotic disorders from two catchment areas with contrasted levels of urbanization. In the more rural area, we also calculated incidence rates in three different groups of population defined by the size of towns in which they live (small, medium and large towns). RESULTS: The annual incidence of psychosis was greater in the urban area (36.02/100000 person-year at risk) than in the rural area (17.2/100000 person-year at risk).Non-affective psychoses were the majority of cases and their incidence was greater in males and younger subjects. The affective psychoses were slightly more frequent in women and showed less variation with age. In the rural centre, greater levels of urbanicity were associated with an increase in the incidence of all psychoses (affective and non-affective). CONCLUSIONS: Our study confirms previous observations of increased incidence rates for non-affective psychoses in the more urbanized areas and suggests that a similar pattern might be present for affective psychoses

Ability of family members to predict patient's consent to critical care research.

International audienceOBJECTIVE: A European Union Directive provides for the designation of a surrogate who can consent to or refuse inclusion of an incapacitated patient in research studies. The accuracy with which surrogates consent to research on behalf of patients has not been evaluated in the intensive care unit (ICU). METHODS: A prospective multicenter study was conducted in ten ICUs of the French Famirea study group between July and October 2004. Two hypothetical studies were simultaneously submitted to the patient, surrogate, and physician at the time that the patient was discharged to a ward. One study involved minimal risk and the other greater-than-minimal risk to the patients. RESULTS: With the minimal risk study there was patient-surrogate discrepancy in 32% of cases and patient-physician discrepancy in 25%. Corresponding figures with the greater-than-minimal risk study were 42% and 46%. None of the collected variables differed significantly between cases with and without patient-surrogate discrepancy. CONCLUSIONS: Family members designated to serve as surrogate decision makers may fail to accurately consent to research for critically ill patients in one-third to nearly one-half of cases