Clinical experience with aminoglycosides in dialysis-dependent patients: risk factors for mortality and reassessment of current dosing practices

Ann Pharmacother. 2011 Nov;45(11):1338-45. doi: 10.1345/aph.1Q403. Epub 2011 Oct 18.

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 all-cause 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 dialysis-dependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminoglycosides / administration & dosage*
  • Aminoglycosides / adverse effects*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects*
  • Female
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Renal Dialysis / methods*
  • Renal Insufficiency / microbiology
  • Renal Insufficiency / therapy*
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents