In vitro evaluations of amikacin: an assessment of the currently used methods of disk diffusion and dilution susceptibility, antimicrobial synergy, and the measurement of amikacin concentrations

Abstract

The amikacin antimicrobial susceptibility tests were reviewed and found to be acceptable for clinical laboratory use. The early change from the 10-μg to the 30-μg diagnostic disk concentration has resulted in reasonable accuracy, according to data from surveys of the College of American Pathologists, and acceptable discrimination between susceptible and resistant microorganisms. Similarly, standardized dilution susceptibility methods have proven acceptable, but great care must be exercised to select an agar medium in which performance was evaluated by the criteria of the National Committee for Clinical Laboratory Standards. Breakpoint concentrations selected as susceptible for amikacin (equal to or less than 16 μg/ml) were based on infected patient pharmacokinetics and previously correlated with patient bacteriologic outcome. Amikacin serum levels have been accurately measured by numerous procedures, including gas-liquid chromatography, radioimmunoassay, radioenzymatic assay, bioassay, and latex agglutination tests. Recent surveys of the College of American Pathologists support the earlier suspicions of lower accuracy and specificity with the bioassay method. Care must be taken to rapidly and appropriately process specimens from patients receiving concurrent high doses of antipseudomonal penicillins because of documented inactivation of some aminoglycosides by these penicillins. Amikacin is less affected by these beta-lactams. Evaluations of the antibacterial activity of amikacin in combination with other antimicrobial agents, principally the beta-lactams, continue to show high rates of enhanced killing or synergy. Although the methods for assessment of synergy have not been standardized, remarkably favorable and similar results between laboratories have been reported.