Therapeutic Drug Monitoring of Gentamicin Peak Concentrations in Critically Ill Patients

Abstract

Gentamicin dosing based on Cmax after the first dose increased %Cther and decreased %Csubther, but did not result in therapeutic Cmax in half of the patients. When simulating a higher starting dose, %Csubther after the first dose decreased, and TDM showed no additional influence. These data suggest that a starting dose of 6 mg/kg should be considered and that repeated Cmax measurements are not of added value.

Aminoglycosides in the Intensive Care Unit: What's New in Population PK Modeling?

“…After assessing the articles for eligibility by applying the inclusion and exclusion criteria, 19 publications were selected. In total, 6, 11, and 5 PopPK models were analyzed for amikacin [16][17][18][19][20][21], gentamicin [21][22][23][24][25][26][27][28][29][30][31] and tobramycin [32][33][34], respectively (Figure 1).…”

“…All 19 studies included in this review used nonlinear mixed effect methods to analyze their data and develop PopPK models. As per Table 2 , a version of NONMEM software was used for the modeling in more than half of the studies (n=10) [19,[22][23][24][25][26][27][32][33][34]. Other software used were NPAG a function from the software Pmetrics (n=2) and the NPEM software (n=2).…”

“…For model evaluation, more than half of these studies only used advanced internal evaluation, such as the bootstrap resampling method (n=10), three studies used both advanced internal and/or external evaluation with several external subjects ranging from 13 to 32 [19,29,33]. Tobramycin pharmacokinetics was described by a two-compartment model (n=3) [32][33][34], while amikacin and gentamicin pharmacokinetics were described by single-compartment (amikacin n=1 [19], gentamicin n=7 [23][24][25][28][29][30][31]) and two-compartment models (amikacin n=5 [16-18, 20, 21], gentamicin n=4 [22,26,27,21]). 7…”

Comment on: Effectiveness and safety of an institutional aminoglycoside-based regimen as empirical treatment of patients with pyelonephritis

“…6 Next to higher dosing, regular peak level monitoring is recommended when aminoglycosides are used for several days to follow up attainment of the PK/PD target, and if not, doses should be increased. 7 It seems that only trough level monitoring was recommended in order to warrant safety. 1 Finally, the protocol recommended dose adjustments based on CL CR , with reductions of up to 4 mg/kg for amikacin and 2.5 mg/kg for gentamicin in patients with a CL CR between 30 and 40 mL/min.…”

Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?

“…Of note, in this low-resistance setting, inappropriate empirical treatment due to antibiotic resistance (based on in vitro susceptibilities of isolated pathogens) occurred in 4% of the patients receiving and not receiving gentamicin, also because the empirical use of carbapenems was higher in the group not using aminoglycosides (15% vs. 4%). Furthermore, the dose used, 5 mg/kg, may be suboptimal for this patient population [10]. Arguably, an observational study cannot rule out residual confounding despite adjustments in multivariable analyses, and the question emerges whether a randomized controlled trial (RCT) is needed to obtain a more definite answer.…”