Recommended dose of arbekacin, an aminoglycoside against methicillin-resistant<i>Staphylococcus aureus</i>, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance

Fukuoka, Noriyasu; Aibiki, Mayuki

doi:10.1111/j.1365-2710.2008.00947.x

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…We showed that, because of PK alterations, a loading dose of ≥ 25 mg/kg of amikacin is necessary to achieve therapeutic peak concentrations in patients with severe sepsis or septic shock. Antimicrobials PKs in ICU patients are significantly different from those in healthy volunteers or less severely ill patients [14,31,32]. Increased cardiac index and interstitial fluid shifts in sepsis result in a larger volume of distribution (V d ), which may reduce plasma antibiotic levels [33].…”

Section: Discussionmentioning

confidence: 99%

“…Although aminoglycoside pharmacokinetics (PKs) have been already described for the treatment of ICU infections, studies on optimal regimens in sepsis patients had several limiting factors [14-18]. Few prospective data are available regarding which aminoglycoside dose should be used to optimize aminoglycoside concentrations in ICU patients with severe sepsis and septic shock with multiple organ dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock

et al. 2010

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IntroductionIt has been proposed that doses of amikacin of >15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients.MethodsThis was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study.ResultsIn 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were >64 μg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 μg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable.ConclusionsAs patients with severe sepsis and septic shock have an increased Vd, a first dose of ≥ 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock

et al. 2010

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“…Karakteristik farmakokinetik antibiotik pada pasien yang dirawat di PICU berbeda signifikan dibandingkan dengan pasien dengan orang sehat atau pasien dengan mild disease/non critically ill (Fukuoka and Aibiki, 2008). Pada pasien critically ill, sangat penting dalam memperhatikan faktor-faktor yang mempengaruhi perubahan patofisiologis dalam parameter farmakokinetik dan farmakodinamik dari antibiotik yang diberikan (Pichala dkk., 2013) pasien anak dengan penyakit penyerta/ komorbid (13,9%) jika dibandingkan dengan mereka yang tidak memiliki penyakit penyerta (6,4%) (El Halal dkk., 2012).…”

Section: Hasil Dan Pembahasanunclassified

Evaluasi Kesesuaian Dosis dan Clinical Outcome Amikasin dan Gentamisin di Picu (Pediatric Intensive Care Unit) RSUP Dr. Sardjito Yogyakarta

Nabila

Puspitasari

Laksanawati

2022

Majalah Farmaseutik

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Pemakaian amikasin dan gentamisin yang memiliki kisaran terapi sempit perlu dilakukan monitoring terapi. Monitoring terapi dilakukan melalui tinjauan secara farmakokinetika dengan menghitung estimasi kadar. Penelitian ini bertujuan untuk melihat estimasi kadar amikasin dan gentamisin pada pasien PICU (Pediatric Intensive Care Unit) dan mengetahui hubungannya terhadap outcome klinis pasien serta kejadian nefrotoksisitas. Penelitian ini merupakan penelitian observational dengan desain cross sectional. Subjek penelitian ini adalah pasien pediatrik yang di rawat di PICU RSUP Dr. Sardjito Yogyakarta periode 2017 – 2019. Jumlah pasien yang memenuhi kriteria inklusi dan eksklusi sebanyak 54 pasien. Hasil estimasi kadar diamati berdasarkan 2 parameter PK-PD yaitu kesesuaian rasio Cmax/MIC dan Cmin>MIC. Hasil dari penelitian ini menunjukkan pada penggunaan amikasin mencapai target rasio Cmax/MIC 17 (74%), dan Cmin > MIC yaitu 3 (13%) pasien. Pada penggunaan gentamisin mencapai target rasio Cmax/MIC 16 (46%), Cmin > MIC yaitu 7 (20%) pasien. Hasil analisis dengan uji Fisher menunjukkan tidak terdapat hubungan yang signifikan kedua parameter tersebut terhadap outcome klinis dengan nilai p > 0.05. Kesesuaian estimasi kadar tidak berpengaruh secara signifikan terhadap kejadian nefrotoksisitas. Tanda-tanda nefrotoksisitas terdapat pada 3 pasien (6%).

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Aminoglycoside-Related Nephrotoxicity and Ototoxicity in Clinical Practice: A Review of Pathophysiological Mechanism and Treatment Options

Hiba²,

Chaudhari³

et al. 2023

Adv Ther

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Recommended dose of arbekacin, an aminoglycoside against methicillin-resistantStaphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance

Cited by 8 publications

References 16 publications

Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock

Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock

Evaluasi Kesesuaian Dosis dan Clinical Outcome Amikasin dan Gentamisin di Picu (Pediatric Intensive Care Unit) RSUP Dr. Sardjito Yogyakarta

Aminoglycoside-Related Nephrotoxicity and Ototoxicity in Clinical Practice: A Review of Pathophysiological Mechanism and Treatment Options

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