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Impact of a High Loading Dose of Amikacin in Patients with Severe Sepsis or Septic Shock
Impact of a High Loading Dose of Amikacin in Patients with Severe Sepsis or Septic Shock
Allou N, Bouteau A, Allyn J, et al. Ann Intensive Care Med 2016; 6: 106.
Study Question: What is the incidence of a peak amikacin concentration (Cmax) 60-80 mg/L after a loading dose in severe sepsis and its impact on mortality?
Study Description: This prospective observational cohort in medical and surgical ICUs at two hospitals in France included patients loaded with amikacin 30 mg/kg using actual body weight if BMI <30 kg/m2 and an adjusted body weight if BMI >30 kg/m2 [Ideal body weight (IBW) + 0.4 (total body weight - IBW)]. Amikacin peak levels were obtained 30 minutes after infusion, and trough levels at 24 hours.
: Of the 110 patients included, Cmax levels 60-80 mg/L were achieved in 41.8%, levels >80 mg/L in 40% and levels <60 mg/L in 18.2%. Pulmonary infection was most common (n=57) with Pseudomonas aeruginosa isolated in 21 patients and Acinetobacter bauannii in 2 patients. Minimum inhibitory concentrations were not collected for any isolated organism to amikacin.
In multivariate analysis, a Cmax >80 mg/L was associated with a higher odds of mortality than a level of 60-80 mg/L (OR 3.96, 95% CI 1.54-10.2), while a Cmax <60 mg/L was not (OR 1.92, 95% CI 0.46-8.24). In survivors, neither Cmax concentrations >80 mg/L nor trough levels >2.5 mg/L were associated with acute kidney injury (AKI).
Conclusion(s): The target Cmax concentration was achieved in 41.8% of patients, but was associated with lower mortality compared to patients with a supratherapeutic level of >80 mg/L.
Perspective: Limitations include lacking evaluation of factors that may impact mortality in patients with sepsis, including timing and appropriateness of antibiotics, duration of antibiotic therapy, and MICs of isolated organisms. Additionally, only the amikacin concentration after the first dose was evaluated. While dosing strategies to achieve targeted amikacin levels should be evaluated given the increasing prevalence of multi-drug resistant organisms, further evaluation of clinical outcomes during an entire course of amikacin therapy is warranted.