In Vitro Activity, Synergism, and Testing Parameters of Amikacin, with Comparisons to Other Aminoglycoside Antibiotics

Abstract

The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 ug/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility ofPseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%o. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.

Pharmacokinetics of Amikacin During Hemodialysis and Peritoneal Dialysis

“…The highest concentrations were found in patients on hemodialysis, which is to be expected from the smaller total body weight. After dialysis the concentration decreased to levels less than 2 ,ug/ml, which is below the minimum inhibitory concentration for various isolates of bacterial strains (11 3. Correlation between the half-life ofamikacin and the decrease in blood urea during hemodialysis and peritoneal dialysis.…”

Emergence in a Burn Center of Populations of Bacteria Resistant to Gentamicin, Tobramycin, and Amikacin: Evidence for the Need for Changes in Zone Diameter Interpretative Standards

“…These disparities are explainable, at least in part, by the demonstrated effect of divalent cation content on the susceptibility of Pseudomonas to gentamicin. Broth media are usually low in divalent cations relative to agar media and yield substantially lower MICs (4,9,10,13,21). This effect is much less marked with members of the Enterobacteriaceae, although total ionic strength may influence the activity of the antibiotic (2).…”

“…Unfortunately, the results of laboratory tests with these antibiotics are subject to some technical variables, and the susceptibility of P. aeruginosa, in particular, depends on the medium used and its cationic content (2,4,9,10,13,21). Many of the earlier studies designed to determine criteria for susceptibility by the diffusion test were performed before the difficulty with the cationic content of media was recognized.…”

Decreased susceptibility to 4'-deoxy-6'-N-methylamikacin (BB-K311) conferred by a mutant plasmid in Escherichia coli

“…Whereas resistance to kanamycin A is conferred enzymatically by adenylylation at its 4'-hydroxyl and 2"-hydroxyl groups, acetylation at its 3-amino and 6'-amino groups, and phosphorylation at its 3'-hydroxyl group (7), the substitution at the 1-amino group, yielding amikacin, abolishes resistance produced by enzymatic modificat-ion at most sites on the kanamycin molecule (7,8,16). Thus, resistance to amikacin by enzymatic modification in gram-negative bacteria has been reported to be limited to strains that produce aminoglycoside 6'-acetyltransferase (7,16).…”