Pharmacy, Health Sciences & Exercise Science
Review of Aminoglycoside Trough Concentrations in Relationship with Nephrotoxicity
Document Type
Oral Presentation
Location
Indianapolis, IN
Subject Area
Pharmacy, Health Sciences & Exercise Science
Start Date
10-4-2015 8:30 AM
End Date
10-4-2015 10:00 AM
Sponsor
Kristen Nichols, Chad Knoderer (Butler University)
Description
Introduction: Aminoglycosides are antibiotics primarily used in the treatment of infections caused by gram-negative bacteria. The most significant adverse effect observed in aminoglycosides is nephrotoxicity. Serum concentration monitoring allows pharmacists and prescribers to tailor each patient's exposure. Varying trough concentration goals have been utilized in clinical studies, but the goal for extended-interval aminoglycoside dosing is for troughs to be undetectable in order to decrease the risk of nephrotoxicity. However, precision of laboratory determinations of aminoglycoside concentrations vary, with a lower limit of detection from 0.01 to 0.49mg/L. The purpose of this study was to define undetectable by determining if there is a relationship between trough concentrations below certain limits of detection and risk of nephrotoxicity in published studies.
Methods: We conducted a literature review on aminoglycoside trough concentration monitoring and toxicity. Articles were identified via a PubMed search with additional references extracted from the bibliographies of the identified articles. Articles were screened for evaluation of nephrotoxicity. Pertinent articles were evaluated to determine trough concentrations detected and the incidence of nephrotoxicity at these concentrations. Lower limits of aminoglycoside concentration detection for each study were recorded if provided. Studies were evaluated to determine what threshold of undetectable was associated with decreased risk of nephrotoxicity.
Results: Fifty-seven studies were reviewed. Only 34 studies addressed both aminoglycoside trough concentrations and nephrotoxicity outcomes. The definition of nephrotoxicity varied among studies, yet was commonly defined as a steady rise in serum creatinine>0.5mg/dL and nonoliguric renal failure. No nephrotoxicity occurred in 18 studies, and 11 of these had an average trough<1mg/dL. Nephrotoxicity did occur in 15/34 studies; 6 of these revealed an average trough>1mg/L. A majority of the studies focused on once daily dosing (ODD) versus multiple daily dosing (MDD). As anticipated, the trough was lower in all ODD groups compared to MDD groups. The average trough for ODD and MDD was 0.75 mg/dL and 1.64 mg/dL respectively. Half of these studies showed more nephrotoxicity in the MDD group. One study reported more toxicity in the ODD group; though this was not shown to be statistically significant. Nephrotoxicity was found to be associated with other risk factors in 7/15 studies, such as duration of therapy, cumulative AUC, or additional nephrotoxic agents.
Conclusion: After conducting this literature review, we cannot determine an exact aminoglycoside trough concentration below which nephrotoxicity is less likely. Nephrotoxicity of aminoglycosides has been related to prolonged duration of therapy and concomitant nephrotoxic agents in addition to elevated trough concentrations.
Review of Aminoglycoside Trough Concentrations in Relationship with Nephrotoxicity
Indianapolis, IN
Introduction: Aminoglycosides are antibiotics primarily used in the treatment of infections caused by gram-negative bacteria. The most significant adverse effect observed in aminoglycosides is nephrotoxicity. Serum concentration monitoring allows pharmacists and prescribers to tailor each patient's exposure. Varying trough concentration goals have been utilized in clinical studies, but the goal for extended-interval aminoglycoside dosing is for troughs to be undetectable in order to decrease the risk of nephrotoxicity. However, precision of laboratory determinations of aminoglycoside concentrations vary, with a lower limit of detection from 0.01 to 0.49mg/L. The purpose of this study was to define undetectable by determining if there is a relationship between trough concentrations below certain limits of detection and risk of nephrotoxicity in published studies.
Methods: We conducted a literature review on aminoglycoside trough concentration monitoring and toxicity. Articles were identified via a PubMed search with additional references extracted from the bibliographies of the identified articles. Articles were screened for evaluation of nephrotoxicity. Pertinent articles were evaluated to determine trough concentrations detected and the incidence of nephrotoxicity at these concentrations. Lower limits of aminoglycoside concentration detection for each study were recorded if provided. Studies were evaluated to determine what threshold of undetectable was associated with decreased risk of nephrotoxicity.
Results: Fifty-seven studies were reviewed. Only 34 studies addressed both aminoglycoside trough concentrations and nephrotoxicity outcomes. The definition of nephrotoxicity varied among studies, yet was commonly defined as a steady rise in serum creatinine>0.5mg/dL and nonoliguric renal failure. No nephrotoxicity occurred in 18 studies, and 11 of these had an average trough<1mg/dL. Nephrotoxicity did occur in 15/34 studies; 6 of these revealed an average trough>1mg/L. A majority of the studies focused on once daily dosing (ODD) versus multiple daily dosing (MDD). As anticipated, the trough was lower in all ODD groups compared to MDD groups. The average trough for ODD and MDD was 0.75 mg/dL and 1.64 mg/dL respectively. Half of these studies showed more nephrotoxicity in the MDD group. One study reported more toxicity in the ODD group; though this was not shown to be statistically significant. Nephrotoxicity was found to be associated with other risk factors in 7/15 studies, such as duration of therapy, cumulative AUC, or additional nephrotoxic agents.
Conclusion: After conducting this literature review, we cannot determine an exact aminoglycoside trough concentration below which nephrotoxicity is less likely. Nephrotoxicity of aminoglycosides has been related to prolonged duration of therapy and concomitant nephrotoxic agents in addition to elevated trough concentrations.