Aminoglycoside resistance: a worldwide perspective

Abstract

Two concerns, neither of which is particularly new, underlie the current reluctance to use aminoglycosides more broadly. First, an undeniable fact is that these compounds can be toxic, particularly in patients with impaired renal function or those receiving other nephrotoxic medications. Second, a more emotional concern is that widespread use of aminoglycosides, particularly the newer compounds that are more resistant to enzymatic inactivation, may engender widespread resistance. In fact, several sources lead one to doubt whether widespread use of potent and highly effective agents like amikacin will by itself increase a clinical reservoir of more resistant microbes. First, the surveillance studies undertaken in many hospitals show some modest reduction in overall aminoglycoside resistance even when a drug like amikacin is used to supplant antecedent compounds of the same class. Second, in institutions where no official surveillance programs have been undertaken but where ongoing surveillance has been maintained, susceptibility to amikacin has remained constant when recent blood isolates are compared with blood isolates from more than 10 years ago. Third, in controlled clinical trials, particularly in immunocompromised patients, the overall emergence of resistance has been remarkably low and contrasts rather strikingly with what has been observed in some monotherapeutic studies of beta-lactam agents. The presence of aminoglycoside-resistant strains cannot be denied, but the circumstances leading to the emergence of such resistance must be carefully assessed, particularly outside of the setting in which these drugs are used as first-line therapy for critically ill patients. For instance, there is substantial evidence to suggest that the topical use of aminoglycosides or the use of these agents when there may be environmental contamination could lead to the emergence of resistance. Before one incriminates the use of any one drug as predisposing to the emergence of resistance, one needs to have more information about the total exposure of a given bacterial population to aminoglycoside therapy. The emergence of resistance to aminoglycosides has been associated with exposure to the more commonly used agents such as gentamicin or tobramycin. With some of the newer beta-lactam agents, the rate of emergence of resistance, unlike that of the aminoglycosides, has appeared to be remarkably high. If the concern about emergence of resistance is genuine, and to maintain consistency of approaches, the infectious disease community should focus more attention on limiting or restricting the use of the more widely used beta-lactam compounds. It seems clear that selective reservation of one compound of an antibiotic class, while all of the other agents belonging to that class are unrestricted, will have little or no impact upon the development of resistance to that class. The overall basis for selecting aminoglycosides as initial empiric therapy should be the likelihood of their efficacy in certain clinical situations, rather than concerns about potential toxicity and the emergence of resistance.