Efficacy and safety of high-dose gentamicin re-dosing in ICU patients receiving haemodialysis

Venisse, Nicolas; Dupuis, Antoine; Badin, J; Robert, R.; Pinsard, M.; Veinstein, Anne

doi:10.1093/jac/dku369

Cited by 8 publications

(9 citation statements)

References 9 publications

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“…When compared with other PK studies with aminoglycosides, 10,17,18 the V and the CLs (interdialytic) were comparable. As expected, the CLs of tobramycin were much lower than the CLs of tobramycin in individuals with kidney function.…”

Section: Discussionmentioning

confidence: 54%

“…7,8 Recently, 2 pharmacokinetic studies performed in critically ill patients showed that administration of gentamicin (6 mg/kg) 30 minutes before the hemodialysis session could allow for adequate exposure targets. 9,10 However, administration of aminoglycosides 30 minutes before hemodialysis is not convenient for most outpatient clinic users and can be complicated. A similar high-dose regimen administered at the beginning of the hemodialysis could be more convenient.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study)

Giroux

Bouchard

Henderson

et al. 2021

Can J Kidney Health Dis

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Background and Objectives: There is a renewed interest in the successful use of aminoglycosides due to increasing resistance in gram-negative infections. Few studies to date have examined the pharmacokinetics (PK) of intradialytic infusions of tobramycin. This study sought to characterize the pharmacokinetic profile of intradialytically administered tobramycin in infected patients receiving chronic intermittent hemodialysis and to determine whether it is possible to achieve favorable PK targets. Design, Setting, Participants, and Measurements: In this prospective pharmacokinetic study, a single dose (5 mg/kg) of tobramycin was administered intradialytically to 11 noncritically ill patients undergoing chronic intermittent hemodialysis. Blood samples were collected at selected time to determine tobramycin serum concentrations. The PK analysis was performed using Phoenix™ NLME. The efficacy exposure outcome for nonsevere gram-negative infections sensitive to tobramycin with a minimum inhibitory concentration ≤1 were maximum concentration (Cmax ≥ 10 mg/L) and area under the curve (AUC24 h > 30 mg⋅h/L). For toxicity, the goal was to identify plasma trough concentrations <2 mg/L. Results: Tobramycin disposition was best described by a one-compartment model using a total clearance composed of the systemic clearance and a transitory hemodialysis clearance. Tobramycin mean (SD) Cmax, trough levels, and AUC24h were 13.1 (1.3) mg/L, 1.32 (0.47) mg/L, and 61 (23) mg⋅h/L, respectively. Monte Carlo simulation run with 1000 virtual patients showed that a 5 mg/kg dose of tobramycin administered intradialytically can outperformed the usual low-dose postdialysis dosing (80% meeting all targets versus <1%, respectively). Conclusions: A single high dose of tobramycin can achieve favorable PK outcome when administered using intradialytic infusions in hemodialysis patients. This practical dosing regimen may represent an effective and safer alternative to the usual dosing in the treatment of nonsevere gram-negative infections.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study)

Giroux

Bouchard

Henderson

et al. 2021

Can J Kidney Health Dis

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“…Therefore, the dose used should be carefully adjusted. Also, gentamicin is not metabolized and eliminated by the kidneys and overdoses can increase the risks of renal toxicity and ototoxicity [325,326]. Routinely, in the pharmaceutical industry, and because of the chemical nature of the gentamicin complex, only the relative percentage of its major constituents are measured by liquid chromatography combined with pulsed electrochemical detection (LC-PED).…”

Section: Bioprocess Development and Biotransformationmentioning

confidence: 99%

Recent progress on the development of antibiotics from the genus Micromonospora

Boumehira

El‐Enshasy

Hacène

et al. 2016

Biotechnol Bioproc E

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The emergence of large number of antimicrobial-resistant organisms has given alarming magnitude. Nature is historically the source of drugs, and microorganisms have provided a significant number of antibiotic compounds, which are used every day in the treatment of many infectious diseases. However, the introduction to the pharmaceutical market of new therapeutic molecules has largely decreased during the last two decades. In this review, antibiotics from the genus Micromonospora are recognized as potential biofactory for new antibiotic production. The Micromonospora has been deeply studied and more than 100 antibiotics isolated from different Micromonospora strains. In addition, comprehensive information about the recent development in the field of analytical, biological and bioinformatics screening tools, which recently used in the discovery of new therapeutic compounds, are provided. It is widely believed that reviving old antibiotics produced by Micromonospora is possible and the study of this genus is still interesting for novel bioactive molecules discovery.

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“…Patients in the intensive care unit (ICU) often require the concomitant administration of several drugs. However, ICU patients display marked differences in pharmacokinetics compared with healthy persons . For example, changes in volume of distribution can result in inadequate plasma drug concentrations, whereas decreased clearance may increase the risk of toxicity .…”

Section: Introductionmentioning

confidence: 99%

“…However, ICU patients display marked differences in pharmacokinetics compared with healthy persons . For example, changes in volume of distribution can result in inadequate plasma drug concentrations, whereas decreased clearance may increase the risk of toxicity . Reduced protein binding resulting from a lower plasma albumin concentration may increase drug clearance thereby lowering the total drug concentration without effect on the unbound drug concentration with the risk of unnecessary increases of drug doses.…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of an intravenous microdialysis catheter for therapeutic drug monitoring of gentamicin and vancomycin

Mast

Nijsten

Alffenaar

et al. 2019

Pharmacology Res & Perspec

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A central venous catheter with a built‐in microdialysis membrane is available for continuous lactate and glucose monitoring in the intensive care unit ( ICU ). As this catheter might also be suitable for repeated measurements of unbound drug levels, we studied in vitro the feasibility of monitoring unbound antibiotic concentrations. The catheter was placed in various media at 37°C spiked with gentamicin or vancomycin. Dialysate fractions were repeatedly collected over 3 hours with a NaCl 0.9% perfusate flow of 5 μL/min. Total and unbound drug concentrations in medium and perfusate were measured by immunoassay. After 60 minutes stable recovery for both drugs was observed, with mean ± SD relative recoveries of vancomycin and gentamicin in human serum of 64% ±0.4% and 73% ±3%. The recoveries of the unbound concentrations were 91% ±3% and 91% ±4%. This intravenous microdialysis system may be a very useful platform for therapeutic drug monitoring in the ICU .

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Efficacy and safety of high-dose gentamicin re-dosing in ICU patients receiving haemodialysis

Cited by 8 publications

References 9 publications

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study)

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study)

Recent progress on the development of antibiotics from the genus Micromonospora

In vitro evaluation of an intravenous microdialysis catheter for therapeutic drug monitoring of gentamicin and vancomycin

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