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Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen

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Abstract

Purpose

Amikacin requires pharmacodynamic targets of peak serum concentration (C max) of 8–10 times the minimal inhibitory concentration, corresponding to a target C max of 60–80 mg/L for the less susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30 % of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient C max in a population of critically ill patients.

Methods

Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of C max < 60 mg/L were identified by mixed model multivariate analysis.

Results

Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 [41–68]) were included. At inclusion, the SOFA score was 8 [6–12], 119 (66 %) episodes required vasopressors, 150 (83 %) mechanical ventilation, and 81 (45 %) renal replacement therapy. The amikacin C max was 69 [54.9–84.4] mg/L. Overall, 60 (33 %) episodes had a C max < 60 mg/L. The risk of C max < 60 mg/L associated with BMI < 25 kg/m2 varied across quarters of inclusion. Independent risk factors for C max < 60 mg/L were a BMI < 25 kg/m2 over the first quarter (odds ratio (OR) 15.95, 95 % confidence interval (CI) [3.68–69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95 % [CI 1.01–1.11], p = 0.018).

Conclusions

Despite an amikacin dose of 25 mg/kg of total body weight, 33 % of patients still had an amikacin C max < 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of C max < 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.

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Acknowledgments

The authors would like to thank Marina Esposito-Farese for statistical advice. The authors would like to thank Jan Devenish for editorial assistance.

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Authors and Affiliations

  1. Service de Réanimation Médicale et des Maladies Infectieuse, Hôpital Bichat–Claude-Bernard, Assistance Publique–Hôpitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, 46 rue Henri Huchard, 75877 cedex 18, Paris, France

    Etienne de Montmollin, Lila Bouadma, Bruno Mourvillier, Eric Mariotte, Sarah Chemam, Michel Wolff & Romain Sonneville

  2. Département d’Epidémiologie et Recherche Clinique, Hôpital Bichat–Claude-Bernard, Assistance Publique–Hôpitaux de Paris, 46 rue Henri Huchard, 75877 cedex 18, Paris, France

    Nathalie Gault & Florence Tubach

  3. INSERM CIC, 1425-EC, UMR 1123 ECEVE, 75018, Paris, France

    Nathalie Gault & Florence Tubach

  4. Université Paris Diderot, PRES Sorbonne Paris Cité, UMR 1123 ECEVE, 75018, Paris, France

    Nathalie Gault & Florence Tubach

  5. Pharmacie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, 46 rue Henri Huchard, Paris, 75877 cedex 18, France

    Laurent Massias & Emmanuelle Papy

Authors
  1. Etienne de Montmollin
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  2. Lila Bouadma
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  3. Nathalie Gault
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  5. Eric Mariotte
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  6. Sarah Chemam
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  7. Laurent Massias
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  8. Emmanuelle Papy
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  9. Florence Tubach
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  10. Michel Wolff
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  11. Romain Sonneville
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Corresponding author

Correspondence to Romain Sonneville.

Additional information

Take home message: An amikacin loading dose of 25 mg/kg is insufficient to reach the pharmacodynamic target in 33 % of critically ill patients, in particular in patients with a positive 24-h fluid balance. When total body weight is used, BMI < 25 kg/m2 tended to be associated with amikacin underdosing. This study suggests the need for tight amikacin serum monitoring in every ICU patient, and higher loading doses in this particular subset of patients.

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de Montmollin, E., Bouadma, L., Gault, N. et al. Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen. Intensive Care Med 40, 998–1005 (2014). https://doi.org/10.1007/s00134-014-3276-x

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  • DOI: https://doi.org/10.1007/s00134-014-3276-x

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