Bayesian Approach to Control of Amikacin Serum Concentrations in Critically Ill Patients with Sepsis

Lugo-Goytia, Gustavo; Castañeda‐Hernández, Gilberto

doi:10.1345/aph.19104

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…This work presents the results of a popPK analysis of amikacin in a population of adults diagnosed with CF. Although the amikacin popPK have been extensively studied in both general pediatric (9-16) and adult (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) populations, our work extends the knowledge to include adult patients with CF specifically. The PK of several antibacterial agents in individuals with CF differ from those in healthy volunteers and other patients (33,34).…”

Section: Discussionmentioning

confidence: 99%

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Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Illamola

Huynh

Liu

et al. 2018

Antimicrob Agents Chemother

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Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

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Section: Discussionmentioning

confidence: 99%

“…Amikacin population pharmacokinetics (popPK) have been extensively studied in pediatric (9)(10)(11)(12)(13)(14)(15)(16) and adult (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) populations. However, the pharmacokinetics (PK) of aminoglycosides change with the disease being treated (30).…”

mentioning

confidence: 99%

Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Illamola

Huynh

Liu

et al. 2018

Antimicrob Agents Chemother

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“…However, when the same approach was used for the adaptive control of aminoglycoside therapy in other patient populations, predictive performance was similar. [7][8][9][10]15,21,31,32,37,38] Methods that rely on the estimation of Vd and CL would appear preferable in patients with variable pharmacokinetics, such as critically ill patients. However, methods based on the use of target AUC have been advocated since the increasing prevalence of once-daily aminoglycoside dosing.…”

Section: Discussionmentioning

confidence: 99%

“…The standard deviation was obtained from the residual error variances used by the Abbottbase software. [13] Vd (l) = 0.39 W (1 + 0.24 Sepsis) 0.23 NA CL (ml/min) = 0.93 CL CR b (1 + 0.22 Trauma) 0.28 3 [10] Vd (l) = 1.5 Apache II score 0.29 NA CL (ml/min) = 44.5 + 0.67 CL CR b -1.29 PEEP -8. 34 Cat 0.41 4 [21] Vd = 0.35 l/kg 0.32 0.15 CL (ml/min per kg) = 0.0417 + 0.815 CL CR b 0.25, 0.4 a Cat, use of catecholamines; CL, clearance; CL CR , creatinine clearance; CV, coefficient of variation; NA, not applicable; PEEP, positive end-expiratory pressure; Vd, volume of distribution; W, total body weight.…”

Section: Population Pharmacokinetic Modelsmentioning

confidence: 99%

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Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

Gatta¹,

Moreno²,

Calvo³

et al. 2009

j pharm pharmacol

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Appropriate Antibiotic Dosage Levels in the Treatment of Severe Sepsis and Septic Shock

Taccone

Hites

Beumier

et al. 2011

Curr Infect Dis Rep

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Antibiotic treatment of critically ill patients remains a significant challenge. Optimal antibacterial strategy should achieve therapeutic drug concentration in the blood as well as the infected site. Achieving therapeutic drug concentrations is particularly difficult when infections are caused by some pathogens, such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative rods, because of their low susceptibility to antimicrobials. In sepsis, pharmacokinetics (PKs) of antibiotics are profoundly altered and may result in inadequate drug concentrations, even when recommended regimens are used, which potentially contribute to increased mortality and spread of resistance. The wide inter-individual PK variability observed in septic patients strongly limits the a priori prediction of the optimal dose that should be administered. Higher than standard dosages are necessary for the drugs, such as β-lactams, aminoglycosides, and glycopeptides, that are commonly used as first-line therapy in these patients to maximize their antibacterial activity. However, the benefit of reaching adequate drug concentrations on clinical outcome needs to be further determined.

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Bayesian Approach to Control of Amikacin Serum Concentrations in Critically Ill Patients with Sepsis

Cited by 12 publications

References 28 publications

Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

Appropriate Antibiotic Dosage Levels in the Treatment of Severe Sepsis and Septic Shock

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