Aminoglycoside Use in Intensive Care Units and Aminoglycoside Nephrotoxicity

Comment Letter 1

We read with interest the study by Oliveira and colleagues (6). In their article, the authors find a rate of aminoglycoside-associated nephrotoxicity of 58% in intensive care unit (ICU) patients who received gentamicin or amikacin and noted that mortality in these patients was higher than in patients without acute kidney injury (AKI) (45% versus 29%; P = 0.003). The authors conclude that aminoglycosides should be avoided or used with extreme caution in patients with other comorbid conditions that may lead to renal insufficiency. Several important limitations of this study should be addressed.

First, the authors examined all patients receiving aminoglycosides and found that nearly 60% had AKI. However, these patients with AKI had significantly higher rates of multiple risk factors other than aminoglycoside exposure than the non-AKI group. Thus, the AKI group was at increased risk for toxicity due to other factors and not solely aminoglycoside exposure. In addition, the authors state that the aim of their study was to assess the prevalence of aminoglycoside-associated nephrotoxicity, yet there was no effort at determining causality. The fact that on average the AKI occurred on or near day 7 of therapy and was nonoliguric in nature does not confirm a causal association between aminoglycosides and AKI. A more relevant comparator group would have been patients who did not receive aminoglycosides but who were matched to “case” aminoglycoside patients on calendar time, hospital location, and length of stay (4). Such a study design would have allowed comorbidities, severities of illness scores, and effects of exposure to concomitant nephrotoxins to be compared between exposed and nonexposed patients. Furthermore, mortality was increased in the AKI group, which was not surprising, as AKI is associated with increased mortality regardless of etiology. Also of note, serum aminoglycoside troughs were not reported, which is problematic, as the optimization of aminoglycoside pharmacokinetics is known to minimize nephrotoxicity (3, 5).

Additionally, the authors included patients with ≥4 days of aminoglycoside therapy. These inclusion criteria may not accurately reflect aminoglycoside utilization, as patients in the ICU frequently receive empirical aminoglycosides for shorter durations, until culture data are returned.

In the era of increasingly multidrug-resistant Gram-negative bacilli, it is important and often necessary to consider aminoglycosides for treatment. Inappropriate empirical therapy is a known risk factor for mortality in critically ill patients, and in many ICUs Gram-negative bacilli that are β-lactam resistant are often also fluoroquinolone resistant. Multiple studies have demonstrated the ability to improve the appropriateness of empirical β-lactam therapy by ∼15% with the addition of an aminoglycoside (1, 2). Therefore, it is crucial that we more accurately determine the risk that aminoglycosides pose to patients.

While we agree that caution should be utilized in prescribing aminoglycosides, we feel that the data presented do not address the question of the independent impact of aminoglycoside exposure on AKI. We also believe that the methods selected did not allow the authors to determine the study's aim, the prevalence of aminoglycoside-induced AKI in ICU patients.