Predictive performance of gentamicin dosing nomograms

Abstract

BackgroundSeveral nomograms have been proposed to facilitate the determination of initial gentamicin dosing regimens in clinical settings. This study aimed to assess the predictive performance of these nomograms in Korean patients.MethodsGentamicin concentrations were determined in 84 patients with infective endocarditis (IE) and in 95 patients with other infections. All patients underwent therapeutic drug monitoring in Seoul National University Hospital from 2006 to 2012. Individual pharmacokinetic parameters were estimated using a Bayesian method, which predicted steady state peak and trough serum concentrations. Six nomograms were evaluated in patients with “other” infections: the Thomson guidelines, Hull-Sarubbi table, and Rule of Eights, for multiple daily dosing; and the Hartford nomogram, Barnes-Jewish Hospital nomogram, and Sanford Guide, for extended-interval dosing. In IE patients, synergistic combination dosing nomograms, based on the American Heart Association dosing interval guidelines, were evaluated.ResultsGentamicin dosing nomograms performed poorly in attaining the target peak serum concentrations. Multiple-daily dosing nomograms predicted peak serum gentamicin concentrations better than did the extended-interval dosing nomograms (31.9%–72.3% vs 4.3%–45.7%, respectively). Similarly, in patients with IE, the once-daily dosing nomogram resulted in a significantly lower percentage of patients achieving target peak gentamicin concentrations than that associated with the thrice-daily dosing nomogram (P=0.0015). All of the multiple-daily dosing, extended-interval dosing, and synergistic combination dosing nomograms predicted the nontoxic target trough concentrations in >80% of patients.ConclusionGentamicin dosing nomograms performed poorly in achieving the target peak serum concentrations. New gentamicin nomograms may be required in patients with IE, particularly for once-daily dosing. Therapeutic drug monitoring is highly recommended for gentamicin to ensure that the target concentrations are achieved.

Dosing of Aminoglycosides in Chronic Kidney Disease and End-Stage Renal Disease Patients Treated with Intermittent Hemodialysis

“…In the case of Gram-positive and most Gram-negative infections other than UTIs, AGs are usually administered in combination with cell wall-targeting agents such as beta-lactam antibiotics or vancomycin rather than as a monotherapy. They are used synergistically to treat endovascular infections caused by Enterococcus spp., Staphylococcus aureus, Streptococcus spp., and Listeria [14,30,[66][67][68][69][70][71][72][73][74][75][76]. An overview of the dosing regimens of AGs for patients with abnormal kidney functions is provided in Tables 3-5.…”

Appropriateness of gentamicin therapeutic drug monitoring at a Middle Eastern tertiary hospital setting: a retrospective evaluation and quality audit

“…The main areas of inappropriate practices were inappropriate sampling times and inappropriate post-analytical actions including inappropriate dose adjustments. Globally, challenges related to gentamicin optimal dosing, monitoring and TDM application in clinical settings continue to be published in the recent literature (Al-Lanqawi et al, 2007 ; Crcek et al, 2019 ; Hartman et al, 2020 ; Kadambari et al, 2011 ; Lee et al, 2014 ; Valitalo et al, 2015 ). Compelling evidence has proven that gentamicin dosing nomograms performed poorly in achieving therapeutic gentamicin pharmacokinetic targets and emphasise the crucial need for appropriate TDM to guide gentamicin dosing in various populations (Al-Lanqawi et al, 2007 ; Lee et al, 2014 ).…”

“…Globally, challenges related to gentamicin optimal dosing, monitoring and TDM application in clinical settings continue to be published in the recent literature (Al-Lanqawi et al, 2007 ; Crcek et al, 2019 ; Hartman et al, 2020 ; Kadambari et al, 2011 ; Lee et al, 2014 ; Valitalo et al, 2015 ). Compelling evidence has proven that gentamicin dosing nomograms performed poorly in achieving therapeutic gentamicin pharmacokinetic targets and emphasise the crucial need for appropriate TDM to guide gentamicin dosing in various populations (Al-Lanqawi et al, 2007 ; Lee et al, 2014 ). For example, a recent systematic review reported decreased target attainment with gentamicin in critically ill children (Hartman et al, 2020 ).…”

Variation in Gentamicin Dosing and Monitoring in Pediatric Units across New South Wales

“… 20 Also, for empirical therapy (<48 hours) monitoring of plasma concentrations is not required. 21 Although the Australian therapeutics guidelines (2016) 22 recommend the use of a computerized method with a dosage adjustment to achieve a target AUC, they also realize that not all hospitals would have access to these computer programs. Hence, nomograms were included and the nomograms continue to be used by some units in NSW.…”