Problems in Determining the Efficacy of Aminoglycosides

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Abstract
Aminoglycosides are an important component of modern antimicrobial therapy, primarily because of their comprehensive activity against clinically significant aerobic gram-negative bacilli. Differences in spectrum, resistance to inactivation by plasmidmediated enzymes, stability against inactivation by penicillins, and pharmacokinetics are used to distinguish currently available agents. Nonetheless, there is little evidence for the superiority of anyone agent in the absence of drug resistance. On the basis of in vitro data, amikacin appears to be the most active aminoglycoside against Enterobacteriaceae, and tobramycin against Pseudomonas aeruginosa. Best results in clinical studies appear to correlate with use of large doses and the achievement of optimal blood levels. Combinations of aminoglycosides with β-lactam agents have been used commonly to treat sepsis in immunocompromised patients, but such studies are hard to interpret since more than one drug was used. Becauseof its resistance to plasmid- mediated enzymes, amikacin is the agent of choice in situations where there is significant resistance to other aminoglycosides. Since the efficacy of aminoglycosides alone in pulmonary, central nervous system, and deep-bone infections is still open to question, combination therapy is strongly recommended.

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