Back to the Future: Using Aminoglycosides Again and How to Dose Them Optimally

Gram-negative organisms have become increasingly resistant to both b-lactam antibiotics and fluoroquinolones. Consequently, aminoglycoside antibiotics have undergone a resurgence in use. Because of the known toxicities of aminoglycoside antibiotics, clinicians have avoided their use, unless no other alternatives were extant. Over the past 2 decades, we have learned much about the relationship between aminoglycoside exposure and the likelihood of a good clinical outcome or the occurrence of nephrotoxicity. For example, minimum inhibitory concentration values 2.0 mg/L lead to unacceptably low probabilities of a good clinical outcome, and infrequent administration of doses (i.e., intervals of 24 h and longer intervals for patients with compromised renal function) plays a central role in minimizing the likelihood of toxicity. Using these new insights, we suggest ways of evaluating the dose and schedule of administration of aminoglycosides in empirical therapy to obtain the highest likelihood of an efficacious and nontoxic therapy. Nosocomial infections caused by gram-negative bacilli have become increasingly difficult to treat over the past 5 years because of the advent of a number of resistance mechanisms that limit the use of some of the best drugs in our armamentarium. Unfortunately, very few new drugs that are active against multidrug-resistant nosocomial gram-negative organisms are expected to be available for 5‐10 years. Consequently, many clinicians are starting to again consider the use of aminoglycoside antibiotics. The commentary in this article applies only to gram-negative organisms. Aminoglycosides were widely used in empirical therapy throughout the 1970s and much of the 1980s. Unfortunately, aminoglycoside use generates a number of toxicities, mostly oto- and nephrotoxicity. It was noted [1] that patients in intensive care units who developed altered renal function had a significantly increased risk of death. Consequently, with the advent of broad-spectrum b-lactams (e.g., third- and fourthgeneration cephalosporins; b-lactam and b-lactamase inhibitor combinations, such as piperacillin and tazobactam; and carbapenems, such as imipenem plus cilastatin and meropenem)