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.

Epidemiology of 62 patients admitted to the intensive care unit after returning from Madagascar.

BACKGROUND: To our knowledge, there is no data on the epidemiology of patients hospitalized in intensive care unit (ICU) after a stay in Madagascar or other low-income countries. It is possible that such data may improve transfer delays and care quality for these patients. METHODS: In a retrospective study, we reviewed the charts of all patients admitted to ICU of the Reunion Island Felix Guyon University Hospital from January 2011 through July 2013. We identified all patients who had stayed in Madagascar during the 6 months prior to ICU admission. RESULTS: Of 1842 ICU patients, 62 (3.4%) had stayed in Madagascar during the 6 months prior to ICU admission. Patients were 76% male and the median age was 60.5 (48.25-64.75) years; patients were more frequently residents of Madagascar than travellers (56.5%). In most cases, patients were not hospitalized or given antibiotics in Madagascar. The most frequent causes of hospitalization were infections including malaria (21%) and lower respiratory infection (11%). Carriage and infection with multidrug resistant (MDR) bacteria on ICU admission were frequent (37% and 9.7%, respectively). The mortality rate in ICU was 21%, and severity acute physiological Score II was 53.5 (37-68). CONCLUSIONS: Patients admitted to ICU after a stay to Madagascar are mainly elderly patients with chronic illnesses, and often foreign residents. The admission causes are specific of the country like malaria, or specific to the population concerned such as cardiovascular accidents that could be prevented.

Obstructive coronary artery disease in patients hospitalized for severe sepsis or septic shock with concomitant acute myocardial infarction.

PURPOSE: It is difficult to differentiate type 1 acute myocardial infarction (AMI) with obstructive coronary artery disease (OCAD) from type 2 AMI in patients admitted for severe sepsis. The aims of this study were to assess the risk factors and prognosis of OCAD in patients admitted to the intensive care unit for severe sepsis with concomitant AMI. MATERIALS AND METHODS: This is a single-center retrospective cohort study including all consecutive patients who were hospitalized for severe sepsis or septic shock between March 2006 and September 2014 and who underwent coronary angiography in the intensive care unit to identify AMI. RESULTS: Overall, 78 (5.5%) of 1418 patients hospitalized for severe sepsis underwent coronary angiography to identify concomitant AMI. Thirty-two patients (41%) had OCAD. Following multivariate analysis, the risk factors of OCAD were peripheral vascular disease (odds ratio [OR] =5.7; 95% confidence interval [CI], 1.1-30.4; P = .042) and at least 2 cardiovascular risk factors (OR = 6.7; 95% CI, 1.9-23.8; P = .003). Obstructive coronary artery disease was associated with a significant mortality increase at 60 days (OR = 8.1; 95% CI, 1.9-30.2; P = .004). CONCLUSIONS: Obstructive coronary artery disease is a poor prognosis factor in patients hospitalized for severe sepsis with concomitant AMI. In this setting, medical treatment should be considered for patients with peripheral vascular disease or with at least 2 cardiovascular risk factors; the need to perform coronary angiography should be considered carefully.