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Single daily dosing of amikacin in an in-vitro model
1Antiinfective Pharmacology Research Unit, University of Rhode Island, Providence.
Abstract:
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.
Insights
Single daily dosing of amikacin combined with azlocillin effectively combats Pseudomonas aeruginosa infections. This combination therapy, particularly with daily amikacin, demonstrated superior bacterial killing compared to standard dosing regimens.
Area of Science:
- Pharmacodynamics
- Microbiology
- Infectious Diseases
Background:
- Standard amikacin dosing involves multiple daily administrations.
- Emergence of antibiotic resistance is a significant clinical challenge.
- Optimizing aminoglycoside dosing strategies is crucial for effective infection control.
Purpose of the Study:
- To compare the pharmacodynamics of single daily amikacin dosing versus standard divided dosing.
- To evaluate the efficacy of amikacin and azlocillin combination therapy against Pseudomonas aeruginosa.
- To assess the impact of dosing regimens on bacterial regrowth and resistance development.
Main Methods:
- Utilized an in-vitro infection model simulating human pharmacokinetic profiles.
- Tested amikacin (single daily vs. divided doses) and azlocillin regimens.
- Studied two strains of Pseudomonas aeruginosa (one sensitive, one resistant to azlocillin).
Main Results:
- Both amikacin regimens showed initial bacterial killing followed by regrowth of resistant subpopulations.
- Azlocillin alone had limited efficacy against the resistant strain.
- Combination regimens prevented bacterial regrowth; single daily amikacin plus azlocillin achieved the most rapid and complete killing, especially against the resistant strain.
Conclusions:
- Single daily dosing of amikacin, when combined with azlocillin, is highly effective against Pseudomonas aeruginosa.
- Combination therapy prevents the emergence of resistant bacterial subpopulations.
- Findings support further clinical investigation into daily aminoglycoside dosing strategies.