Single daily dosing of amikacin in an in-vitro model.
The pharmacodynamics of amikacin given as a single daily dose was compared with standard divided dosing in an in-vitro model of infection. This model allows the exposure of log phase bacteria to changing concentrations of antibiotics that simulate the kinetics of the drugs in human patients. Two strains of Pseudomonas aeruginosa, one sensitive and one resistant to azlocillin were studied (MICs for amikacin were 16 and 8 mg/l respectively). Simulated drug regimens included: amikacin 400 mg q 8 h; amikacin 1.2 g q 24 h; and azlocillin 4 g q 12 h. Each regimen alone and both combinations of amikacin plus azlocillin were studied. With both amikacin regimens initial rapid killing was followed by regrowth of resistant subpopulations. Azlocillin alone produced minimal killing of the resistant strain and moderate killing with ultimate bacteriostasis of the susceptible strain. Bacterial regrowth was prevented with both combination regimens with the single daily dose of amikacin plus azlocillin producing the most rapid and complete killing, especially of the azlocillin resistant strain. These data support further clinical studies of single daily dosing of aminoglycosides.
Dudley
M N
MN
Antiinfective Pharmacology Research Unit, University of Rhode Island, Providence.
Zinner
S H
SH
D000583:Amikacin / Q000008:administration & dosage* / Q000494:pharmacology; D001390:Azlocillin / Q000008:administration & dosage* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
D000583:Amikacin; D001390:Azlocillin