Aminoglycoside Dosing and Volume of Distribution in Critically Ill Surgery Patients

Grucz, Traci; Kruer, Rachel; Bernice, Fidelia; Lipsett, Pamela A.; Dorman, Todd; Sugrue, David; Jarrell, Andrew

doi:10.1089/sur.2020.012

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…The estimated normal V d for amikacin is 0.25 L/kg in the general population. However, amikacin's V d is shown to be higher in the intensive care unit patients, 8 as also confirmed by the results of this study. The preliminary findings of our study did not show a significant correlation between the IAP with any of the pharmacokinetic parameters.…”

supporting

confidence: 86%

Can Intra-abdominal Pressure Predict the Pharmacokinetics of Aminoglycosides in Critically Ill Patients With Intra-abdominal Sepsis?

Shahrami

Arabzadeh

Najmeddin

et al. 2021

American Journal of Therapeutics

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supporting

confidence: 86%

Can Intra-abdominal Pressure Predict the Pharmacokinetics of Aminoglycosides in Critically Ill Patients With Intra-abdominal Sepsis?

Shahrami

Arabzadeh

Najmeddin

et al. 2021

American Journal of Therapeutics

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“…Moreover, burn injuries altered the pharmacokinetics of amikacin [ 76 ] and tobramycin [ 77 ]. Those changes require higher individualized doses [ 78 , 79 , 80 , 81 ] and, more importantly, may influence the tissue penetration of drugs.…”

Section: Resultsmentioning

confidence: 99%

Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part II

et al. 2022

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In patients that are admitted to intensive care units (ICUs), the clinical outcome of severe infections depends on several factors, as well as the early administration of chemotherapies and comorbidities. Antimicrobials may be used in off-label regimens to maximize the probability of therapeutic concentrations within infected tissues and to prevent the selection of resistant clones. Interestingly, the literature clearly shows that the rate of tissue penetration is variable among antibacterial drugs, and the correlation between plasma and tissue concentrations may be inconstant. The present review harvests data about tissue penetration of antibacterial drugs in ICU patients, limiting the search to those drugs that mainly act as protein synthesis inhibitors and disrupting DNA structure and function. As expected, fluoroquinolones, macrolides, linezolid, and tigecycline have an excellent diffusion into epithelial lining fluid. That high penetration is fundamental for the therapy of ventilator and healthcare-associated pneumonia. Some drugs also display a high penetration rate within cerebrospinal fluid, while other agents diffuse into the skin and soft tissues. Further studies are needed to improve our knowledge about drug tissue penetration, especially in the presence of factors that may affect drug pharmacokinetics.

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“…Strikingly, a large review from 2017 of PPK studies on aminoglycosides identified no studies that showed a correlation between estimated or predicted PK/PD target attainment and clinical success [ 3 ]. Two more recent studies specifically focusing on ICU patients also failed to find this correlation; both studies also included patients treated with amikacin or tobramycin and used aminoglycosides as part of combination therapy [ 79 , 82 ]. The failure to identify an association between target attainment and clinical efficacy may be due to the fact that gentamicin is often used as part of short courses of empirical combination therapy and rarely as targeted monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In multiple studies evaluating aminoglycoside efficacy in critically ill patients, no significant correlation was found between PK/PD target attainment and clinical outcome [ 79 , 81 , 82 ]. The largest of these studies was a prospective observational cohort study in 59 intensive care units that included 931 patients on aminoglycosides, of which 303 received gentamicin.…”

Section: Pharmacokinetics In Critically Ill Patientsmentioning

confidence: 99%

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

et al. 2022

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Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of shortterm empirical combination therapy. Gentamicin dosing schemes still need refinement, especially for subpopulations where pharmacokinetics can differ from pharmacokinetics in the general adult population: obese patients, critically ill patients, paediatric patients, neonates, elderly patients and patients on dialysis. This review summarizes the clinical pharmacokinetics of gentamicin in these patient populations and the consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria, highlighting new insights from the last 10 years. In this period, several new population pharmacokinetic studies have focused on these subpopulations, providing insights into the typical values of the most relevant pharmacokinetic parameters, the variability of these parameters and possible explanations for this variability, although unexplained variability often remains high. Both dosing schemes and pharmacokinetic/pharmacodynamic (PK/PD) targets varied widely between these studies. A gentamicin starting dose of 7 mg/kg based on total body weight (or on adjusted body weight in obese patients) appears to be the optimal strategy for increasing the probability of target attainment (PTA) after the first administration for the most commonly used PK/PD targets in adults and children older than 1 month, including critically ill patients. However, evidence that increasing the PTA results in higher efficacy is lacking; no studies were identified that show a correlation between estimated or predicted PK/PD target attainment and clinical success. Although it is unclear if performing therapeutic drug monitoring (TDM) for optimization of the PTA is of clinical value, it is recommended in patients with highly variable pharmacokinetics, including patients from all subpopulations that are critically ill (such as elderly, children and neonates) and patients on intermittent haemodialysis. In addition, TDM for optimization of the dosing interval, targeting a trough concentration of at least < 2 mg/L but preferably < 0.5-1 mg/L, has proven to reduce nephrotoxicity and is therefore recommended in all patients receiving more than one dose of gentamicin. The usefulness of the daily area under the plasma concentration-time curve for predicting nephrotoxicity should be further investigated. Additionally, more research is needed on the optimal PK/PD targets for efficacy in the clinical situations in which gentamicin is currently used, that is, as monotherapy for urinary tract infections or as part of short-term combination therapy.

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Aminoglycoside Dosing and Volume of Distribution in Critically Ill Surgery Patients

Cited by 6 publications

References 24 publications

Can Intra-abdominal Pressure Predict the Pharmacokinetics of Aminoglycosides in Critically Ill Patients With Intra-abdominal Sepsis?

Can Intra-abdominal Pressure Predict the Pharmacokinetics of Aminoglycosides in Critically Ill Patients With Intra-abdominal Sepsis?

Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part II

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

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