Expérience clinique avec les aminosides chez les patients dialysés: Facteurs de risque de mortalité et réévaluation des pratiques actuelles d'ajustement posologique

Translated title of the contribution: Clinical experience with aminoglycosides in dialysis-dependent patients: Risk factors for mortality and reassessment of current dosing practices

Brett H. Heintz, George Richard Thompson, William E. Dager

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. OBJECTIVE: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. METHODS: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for allcause 30-day mortality. RESULTS: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038), and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. CONCLUSIONS: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysisdependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.

Original languageSpanish
Pages (from-to)1338-1345
Number of pages8
JournalAnnals of Pharmacotherapy
Volume45
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Aminoglycosides
Dialysis
Mortality
Therapeutics
Catheters
Tobramycin
Microbial Sensitivity Tests
Bacteremia
Infection
Gentamicins
Renal Insufficiency
Multivariate Analysis
Logistic Models
Regression Analysis

Keywords

  • Aminoglycosides
  • Antimicrobials
  • Hemodialysis
  • Pharmacodynamics
  • Pharmacokinetics
  • Renal replacement therapy

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

@article{0c4dac448475430d9182edcc0c7da3ff,
title = "Exp{\'e}rience clinique avec les aminosides chez les patients dialys{\'e}s: Facteurs de risque de mortalit{\'e} et r{\'e}{\'e}valuation des pratiques actuelles d'ajustement posologique",
abstract = "BACKGROUND: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. OBJECTIVE: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. METHODS: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for allcause 30-day mortality. RESULTS: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5{\%}. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038), and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. CONCLUSIONS: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysisdependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.",
keywords = "Aminoglycosides, Antimicrobials, Hemodialysis, Pharmacodynamics, Pharmacokinetics, Renal replacement therapy",
author = "Heintz, {Brett H.} and Thompson, {George Richard} and Dager, {William E.}",
year = "2011",
month = "11",
doi = "10.1345/aph.1Q403",
language = "Spanish",
volume = "45",
pages = "1338--1345",
journal = "Annals of Pharmacotherapy",
issn = "1060-0280",
publisher = "Harvey Whitney Books Company",
number = "11",

}

TY - JOUR

T1 - Expérience clinique avec les aminosides chez les patients dialysés

T2 - Facteurs de risque de mortalité et réévaluation des pratiques actuelles d'ajustement posologique

AU - Heintz, Brett H.

AU - Thompson, George Richard

AU - Dager, William E.

PY - 2011/11

Y1 - 2011/11

N2 - BACKGROUND: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. OBJECTIVE: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. METHODS: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for allcause 30-day mortality. RESULTS: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038), and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. CONCLUSIONS: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysisdependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.

AB - BACKGROUND: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. OBJECTIVE: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. METHODS: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for allcause 30-day mortality. RESULTS: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038), and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. CONCLUSIONS: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysisdependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.

KW - Aminoglycosides

KW - Antimicrobials

KW - Hemodialysis

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Renal replacement therapy

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U2 - 10.1345/aph.1Q403

DO - 10.1345/aph.1Q403

M3 - Article

C2 - 22010003

AN - SCOPUS:80155194882

VL - 45

SP - 1338

EP - 1345

JO - Annals of Pharmacotherapy

JF - Annals of Pharmacotherapy

SN - 1060-0280

IS - 11

ER -