Abstract
This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety. For all recommended dosages evaluated, efficacy and safety criteria of amikacin dosage proposed were not achieved simultaneously in most of the clinical scenarios evaluated. Furthermore, a significant impact of albumin was identified: The higher is the albumin, (i) the higher will be the PTA for maximum concentration/minimum inhibitory concentration (Cmax/MIC), (ii) the lower will be the PTA for the time period with drug concentration exceeding MIC (T>MIC) and (iii) the lower will be the PTA for toxicity (minimum concentration). Thus, accounting for albumin effect might be of interest for future amikacin dosing guidelines updates. In addition, AMKnom, an amikacin nomogram builder based on PKPD criteria, has been developed and is freely available to help evaluating dosing recommendations.
Highlights
Amikacin is one of the most effective aminoglycoside antibiotics used against severe gram-negative bacterial infections and initial empirical antimicrobial treatments
Our results showed that intrinsic factors such as total bodyweight (TBW), ALB and CKDEPI had a significant impact on efficacy and safety of amikacin treatments
Our findings show a significant influence of ALB on amikacin dosage regimens: considering the same renal function, patients with hypoalbuminemia should receive higher doses than normoalbuminemic ones for warrantying a comparable treatment efficacy
Summary
Amikacin is one of the most effective aminoglycoside antibiotics used against severe gram-negative bacterial infections and initial empirical antimicrobial treatments. It is commonly administered with β-lactam antibiotics to extend the antimicrobial activity spectrum against multidrug-resistant pathogens such as Pseudomonas aeruginosa [1,2]. Optimizing amikacin treatment has been recently proposed by clinicians, driven by the increase of resistance to alternative antibiotic drugs [3]. A ratio between the area under the concentration-time curve (AUC) and the MIC (AUC/MIC). ≥ 70 (up to 80–100 in amikacin monotherapy or in critically ill patients with high-bacterial burden infections) and a time for which concentration exceeds the MIC (T>MIC ) of at least. AUC/MIC criteria has been more commonly applied for vancomycin and fluoroquinolones while an insufficient T>MIC
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